Journal articles: 'Platinum group. Antineoplastic agents'

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Odularu, Ayodele T., Peter A. Ajibade, Johannes Z. Mbese, and Opeoluwa O. Oyedeji. "Developments in Platinum-Group Metals as Dual Antibacterial and Anticancer Agents." Journal of Chemistry 2019 (November 6, 2019): 1–18. http://dx.doi.org/10.1155/2019/5459461.

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Platinum-group (PG) complexes have been used as antibacterial and anticancer agents since the discovery of cisplatin. The science world still requires improvement on these complexes because of multidrug and antineoplastic resistances. This review observes discoverers and history of these platinum-group metals (PGMs), as well as their beneficial applications. The focus of this study was biological applications of PGMs in relation to human health. Sandwich and half-sandwich PGM coordination compounds and their metal nanoparticles give improved results for biological activities by enhancing efficient delivery of both antibacterial and anticancer drugs, as well as luminescent bioimaging (biomarkers) for biological identifications.

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César, Bruno Nogueira, and Marcelino de Souza Durão Júnior. "Acute kidney injury in cancer patients." Revista da Associação Médica Brasileira 66, suppl 1 (2020): s25—s30. http://dx.doi.org/10.1590/1806-9282.66.s1.25.

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SUMMARY The increasing prevalence of neoplasias is associated with new clinical challenges, one of which is acute kidney injury (AKI). In addition to possibly constituting a clinical emergency, kidney failure significantly interferes with the choice and continuation of antineoplastic therapy, with prognostic implications in cancer patients. Some types of neoplasia are more susceptible to AKI, such as multiple myeloma and renal carcinoma. In cancer patients, AKI can be divided into pre-renal, renal (intrinsic), and post-renal. Conventional platinum-based chemotherapy and new targeted therapy agents against cancer are examples of drugs that cause an intrinsic renal lesion in this group of patients. This topic is of great importance to the daily practice of nephrologists and even constitutes a subspecialty in the field, the onco-nephrology.

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Azab, Belal, Anood Alassaf, Abdulrahman Abu-Humdan, Zain Dardas, Hashem Almousa, Mohammad Alsalem, Omar Khabour, Hana Hammad, Tareq Saleh, and Abdalla Awidi. "Genotoxicity of cisplatin and carboplatin in cultured human lymphocytes: a comparative study." Interdisciplinary Toxicology 12, no. 2 (October 1, 2019): 93–97. http://dx.doi.org/10.2478/intox-2019-0011.

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Abstract Cisplatin and carboplatin are integral parts of many antineoplastic management regimens. Both platinum analogues are potent DNA alkylating agents that robustly induce genomic instability and promote apoptosis in tumor cells. Although the mechanism of action of both drugs is similar, cisplatin appears to be more cytotoxic. In this study, the genotoxic potential of cisplatin and carboplatin was compared using chromosomal aberrations (CAs) and sister-chromatid exchange (SCE) assays in cultured human lymphocytes. Results showed that cisplatin and carboplatin induced a significant increase in CAs and SCEs compared to the control group (p<0.01). Levels of induced CAs were similar in both drugs; however, the magnitude of SCEs induced by cisplatin was significantly higher than that induced by carboplatin (p<0.01). With respect to the mitotic and proliferative indices, both cisplatin and carboplatin significantly decreased mitotic index (p<0.01) without affecting the proliferative index (p>0.05). In conclusion, cisplatin was found to be more genotoxic than carboplatin in the SCE assay in cultured human lymphocytes, and that might explain the higher cytotoxicity of cisplatin.

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Li, Lu, Sheng Nie, Chen Ren, Yanqin Li, and Dehua Wu. "The incidence, risk factors and outcomes of chemotherapy related acute kidney injury in China." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e24161-e24161. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e24161.

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e24161 Background: Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. However, comprehensive data on the epidemiology and outcomes of chemotherapy related acute kidney Injury in China is lacking. Methods: We conducted a nationwide cohort study of hospitalized patients from 25 general and children’s hospitals in China during 2013-2015. Patient-level data were obtained from the electronic hospitalization information system, prescription database and laboratory databases of all cancer patients who received chemotherapy and had at least two serum creatinine tests within any 7-day window during the hospitalization. AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria. The incidence of AKI in patients with various type of cancer and chemotherapeutic agents was examined. The outcomes of AKI, including in-hospital mortality, death after discharge, kidney recovery, and length of stay, were also assessed. Results: A total of 23,232 cancer patients, including 3,120 children ( < 18 years old), 16,310 adult (19-65 years old) and 3,802 elderly patients ( > 65 years old), were analyzed. Platinum compounds and pyrimidine analogues were the most common used chemotherapy agents for cancer patients. The overall incidence of AKI was 4.9%. Patients with urinary system malignancy (12.3%), hematological malignancy (10.2%) and nerve motor system malignancy (4.1%) have the highest incidence of HA-AKI. The top three types of chemotherapy drugs with the highest incidence of AKI were Purine analogues (30.1%), folic acid analogues (15.3%) and combinations of antineoplastic agents (14.1%). The nephrotoxicity of chemotherapy drugs was different among age groups. AKI is associated with a higher risk of in-hospital mortality and death after discharge. Conclusions: The risk of AKI in cancer patients varied in different age group, type of cancer and chemotherapeutic agents.

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Bakalova, Adriana G., Rossen T. Buyukliev, Rositsa P. Nikolova, Boris L. Shivachev, Rositsa A. Mihaylova, and Spiro M. Konstantinov. "Synthesis, Spectroscopic Properties, Crystal Structure And Biological Evaluation of New Platinum Complexes with 5-methyl-5-(2-thiomethyl)ethyl Hydantoin." Anti-Cancer Agents in Medicinal Chemistry 19, no. 10 (October 24, 2019): 1243–52. http://dx.doi.org/10.2174/1871520619666190214103345.

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Background: The accidental discovery of Cisplatin’s growth-inhibiting properties a few decades ago led to the resurgence of interest in metal-based chemotherapeutics. A number of well-discussed factors such as severe systemic toxicity and unfavourable physicochemical properties further limit the clinical application of the platinating agents. Great efforts have been undertaken in the development of alternative platinum derivatives with an extended antitumor spectrum and amended toxicity profile as compared to the reference drug cisplatin. The rational design of conventional platinum analogues and the re-evaluation of the empirically derived “structure- activity” relationships allowed for the synthesis of platinum complexes with great diversity in structural characteristics, biochemical stability and antitumor properties. Methods: The new compounds have been studied by elemental analyses, IR, NMR and mass spectral analyses. The structures of the organic compound and one of the new mixed/ammine Pt(II) complexes were studied by X-ray diffraction analysis. The cytotoxic effects of the compounds were studied vs. the referent antineoplastic agent cisplatin against four human tumour cell lines using the standard MTT-dye reduction assay for cell viability. The most promising complex 3 was investigated for acute toxicity in male and female H-albino-mice models. Results: A new organic compound (5-methyl-5-(2-thiomethyl)ethyl hydantoin) L bearing both S- and Ncoordinating sites and three novel platinum complexes, 1, 2 and 3 were synthesized and studied. Spectral and structural characterization concluded monodentate S-driven coordination of the ligand L to the metal center in complexes 1 and 2, whereas the same was acted as a bidentate N,S-chelator in complex 3. Ligand L crystallizes in the tetragonal space group I41/a (No 88) with one molecule per asymmetric unit. While complex 3 crystallizes in the monoclinic space group P21/c (No 14) with one molecule per asymmetric unit. In the same complex 3, the platinum ion coordinates an L ligand, a chloride ion and an ammonia molecule. In the in vitro experiments, the tested L and complexes 1 and 2 exhibited negligible cytotoxic activity in all tumor models. Accordingly, complex 3 is twice as potent as cisplatin in the HT-29 cells and is at least as active as cisplatin on the MDA-MB-231 breast cancer cell line. In the in vivo toxicity estimation of complex 3 no signs of common toxicity were observed. Conclusion: The Pt(II)-bidentate complex 3 exhibited significant cytotoxic potential equaling or surpassing that of the reference drug cisplatin in all the tested tumor models. Negligible anticancer activity on the screened tumor types has been shown by the ligand L and its Pt(II) and Pt(IV) complexes 1 and 2, respectively. Our study on the acute toxicity of the most active complex 3 proved it to be non-toxic in mice models.

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Markman, Maurie. "Toxicities of the platinum antineoplastic agents." Expert Opinion on Drug Safety 2, no. 6 (November 2003): 597–607. http://dx.doi.org/10.1517/14740338.2.6.597.

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Makrilia, Nektaria, Ekaterini Syrigou, Ioannis Kaklamanos, Leonidas Manolopoulos, and Muhammad Wasif Saif. "Hypersensitivity Reactions Associated with Platinum Antineoplastic Agents: A Systematic Review." Metal-Based Drugs 2010 (September 20, 2010): 1–11. http://dx.doi.org/10.1155/2010/207084.

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Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the first-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a significant increase in the incidence of hypersensitivity reactions, which are defined as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, flushing, abdominal cramping, itchy palms, and back pain are common symptoms. Cardiovascular and respiratory complications can prove fatal. Multiple pathogenetic mechanisms have been suggested. Hypersensitivity usually appears after multiple infusions, suggesting type I allergic reactions; however, other types of hypersensitivity also seem to be implicated. Several management options are available to treating physicians: discontinuation of chemotherapy, premedication, prolonging of infusion duration, desensitization protocols, and replacement with a different platinum compound after performing skin tests that rule out cross-reactions among platinum agents.

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Fanelli, Mirco, Mauro Formica, Vieri Fusi, Luca Giorgi, Mauro Micheloni, and Paola Paoli. "New trends in platinum and palladium complexes as antineoplastic agents." Coordination Chemistry Reviews 310 (March 2016): 41–79. http://dx.doi.org/10.1016/j.ccr.2015.11.004.

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Bakhonsky, Vladyslav V., Aleksander A. Pashenko, Jonathan Becker, Heike Hausmann, Huub J. M. De Groot, Herman S. Overkleeft, Andrey A. Fokin, and Peter R. Schreiner. "Synthesis and antiproliferative activity of hindered, chiral 1,2-diaminodiamantane platinum(ii) complexes." Dalton Transactions 49, no. 40 (2020): 14009–16. http://dx.doi.org/10.1039/d0dt02391d.

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Fortner, Clarence L., and Paul J. Vilk. "Aspects of Investigational Antineoplastic Agents." Journal of Pharmacy Practice 4, no. 1 (February 1991): 64–71. http://dx.doi.org/10.1177/089719009100400107.

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Investigational drugs are regulated by the Food and Drug Administration (FDA) and are not available for widespread patient use. They are screened and evaluated extensively before they are administered to humans in clinical trials. The clinical development process is divided into three phases: phase I, II, and III. Protocols for the investigational agent in each of these phases must be approved by an institutional review board and the patient must be informed of the risks of the study and sign an informed consent document. Once adequate clinical data are collected and analyzed, the information is submitted to the FDA for their review and approval for marketing. Prior to that approval, the FDA may approve broader distribution of the drug for specific indications under a Treatment Investigational New Drug (IND) or the National Cancer Institute's (NCI) group C mechanism. Pharmacists can play a unique role during development of the Treatment IND by contributing to design of the protocol and screening patient qualifications. The investigator of the clinical trial has responsibility for the conduct of the clinical trial and must comply with FDA regulations and sponsor policies. This is a US government work. There are no restrictions on its use.

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Zajączkowska, Renata, Magdalena Kocot-Kępska, Wojciech Leppert, Anna Wrzosek, Joanna Mika, and Jerzy Wordliczek. "Mechanisms of Chemotherapy-Induced Peripheral Neuropathy." International Journal of Molecular Sciences 20, no. 6 (March 22, 2019): 1451. http://dx.doi.org/10.3390/ijms20061451.

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited. There are six main substance groups that cause damage to peripheral sensory, motor and autonomic neurons, which result in the development of CIPN: platinum-based antineoplastic agents, vinca alkaloids, epothilones (ixabepilone), taxanes, proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). Among them, the most neurotoxic are platinum-based agents, taxanes, ixabepilone and thalidomide; other less neurotoxic but also commonlyused drugs are bortezomib and vinca alkaloids. This paper reviews the clinical picture of CIPN and the neurotoxicity mechanisms of the most common antineoplastic agents. A better understanding of the risk factors and underlying mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.

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De Almeida, Mauro, Ana Fontes, Richard Berg, Eloi César, Emanoel De Castro Antunes Felício, and José De Souza Filho. "Synthesis of Platinum Complexes from N-Benzyl-1,3-Propanediamine Derivatives, Potential Antineoplastic Agents." Molecules 7, no. 4 (April 30, 2002): 405–11. http://dx.doi.org/10.3390/70400405.

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Hall, Amy L., Paul A. Demers, George Astrakianakis, Calvin Ge, and Cheryl E. Peters. "Estimating National-Level Exposure to Antineoplastic Agents in the Workplace: CAREX Canada Findings and Future Research Needs." Annals of Work Exposures and Health 61, no. 6 (June 8, 2017): 656–58. http://dx.doi.org/10.1093/annweh/wxx042.

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AbstractObjectives:Occupational exposure to antineoplastic agents occurs in various environments and is associated with increased cancer risk and adverse reproductive outcomes. National-level information describing the location and extent of occupational exposure to antineoplastic agents is unavailable in Canada and most other countries. CAREX Canada aimed to estimate the prevalence and relative levels of occupational exposures to antineoplastic agents across work setting, occupation, and sex.Methods:‘Exposure’ was defined as any potential for worker contact with antineoplastic agents. Baseline numbers of licensed workers were obtained from their respective professional bodies. For unlicensed workers, Census data or data extrapolated from human resources reports (e.g., staffing ratios) were used. Prevalence was estimated by combining population estimates with exposure proportions from peer-reviewed and grey literature. Exposure levels (classified as low, moderate, and high) by occupation and work setting were estimated qualitatively by combining estimates of contact frequency and exposure control practices.Results:Approximately 75000 Canadians (0.42% of the total workforce) are estimated as occupationally exposed to antineoplastic agents; over 75% are female. The largest occupational group exposed to antineoplastic agents is community pharmacy workers, with 30200 exposed. By work setting, 39000 workers (52% of all exposed) are located in non-hospital settings; the remaining 48% are exposed in hospitals. The majority (75%) of workers are in the moderate exposure category.Conclusions:These estimates of the prevalence and location of occupational exposures to antineoplastic agents could be used to identify high-risk groups, estimate disease burden, and target new research and prevention activities. The limited secondary data available for developing these estimates highlights the need for increased quantitative measurement and documentation of antineoplastic agent contamination and exposure, particularly in work environments where use is emerging.

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Amir, Eitan, Bostjan Seruga, Joaquin Martinez-Lopez, Ryan Kwong, Atanasio Pandiella, Ian F. Tannock, and Alberto Ocaña. "Oncogenic Targets, Magnitude of Benefit, and Market Pricing of Antineoplastic Drugs." Journal of Clinical Oncology 29, no. 18 (June 20, 2011): 2543–49. http://dx.doi.org/10.1200/jco.2011.35.2393.

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Purpose The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported. Patients and Methods Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the US Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared. Results For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P < .001) and OS (P = .02). The median monthly prices for standard doses of drugs were $5,375 for group A, $5,644 for group B, and $6,584 for group C (P = .87). Conclusion New agents with specific molecular targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.

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Kushev, Daniel N., Nadejda C. Spassovska, Svetoslav I. Taxirov, and Konstantin C. Grancharov. "Cytotoxicity and Antitumor Activity of Platinum(II) Complexes of Aromatic and Cycloalkanecarboxylic Acid Hydrazides." Zeitschrift für Naturforschung C 52, no. 1-2 (February 1, 1997): 49–54. http://dx.doi.org/10.1515/znc-1997-1-209.

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AbstractNew platinum(II) complexes of cyclohexanecarboxylic acid hydrazide (chcah) were synthesized and characterized by elemental analysis, IR. and 1H NMR spectra. Their inhibitory effects on cell growth and macromolecular synthesis of Friend leukemia cells in culture as well as the in vivo antitumor activity towards L1210 leukemia in mice were compared with those of complexes containing differently substituted aromatic acid hydrazides. Some of the complexes exhibited antineoplastic activity. No correlation between the in vitro cytotoxicity and the in vivo antitumor activity was found. However, there was a relationship between the in vitro macromolecular synthesis inhibition profile and the in vivo antineoplastic effect, similar to that of cisplatin. On the other hand, only agents containing one ammine ligand were active in vivo. The substitution of the aromatic ring by a cycloalkane residue increased significantly the antitumor effect, with [Pt(NH3)(chcah)Cl2] being the most active compound in this study.

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Schweer, David, J. Robert McCorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick Ueland, and Jill Kolesar. "Mithramycin and Analogs for Overcoming Cisplatin Resistance in Ovarian Cancer." Biomedicines 9, no. 1 (January 12, 2021): 70. http://dx.doi.org/10.3390/biomedicines9010070.

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Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, in the treatment of platinum-resistant ovarian cancer.

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Donnelly, Erling T., Yanfeng Liu, and Sara Rockwell. "Efaproxiral (RSR13) Plus Oxygen Breathing Increases the Therapeutic Ratio of Carboplatin in EMT6 Mouse Mammary Tumors." Experimental Biology and Medicine 231, no. 3 (March 2006): 317–21. http://dx.doi.org/10.1177/153537020623100312.

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Carboplatin, a member of the platinum family of alkylating agents, is often used in combination with radiotherapy. Some studies, including a recent publication from our laboratory, have suggested that the cytotoxic effects of platinum compounds may be altered by changes in the post-treatment oxygenation. The study reported here assessed whether post-treatment changes in tumor oxygenation caused by oxygen breathing alone or in combination with efaproxiral (RSR13) altered the effects of carboplatin. Efaproxiral, which allosterically modifies hemoglobin-oxygen binding to increase tumor pO2, has been shown to increase the effects of radiation in animal tumor models and is in a second, confirmatory phase III clinical trial as an adjuvant to radiotherapy. These studies with EMT6 tumors in BALB/c Rw mice used clonogenic assays to assess tumor cell survival and tumor growth studies to assess antineoplastic activity and treatment-related toxicity. Efaproxiral plus oxygen breathing for 5 hrs after carboplatin treatment significantly increased the antineoplastic effects of carboplatin. The increased antineoplastic effects of carboplatin produced by efaproxiral plus oxygen breathing occurred without a concomitant increase in host toxicity. These findings suggest that the increases in tumor oxygenation produced by Efaproxiral plus oxygen breathing increased the therapeutic ratio of carboplatin.

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Pažout, Richard, Jaroslav Maixner, Michaela Hrdá, Tereza Loužilová, and Petr Kačer. "A bromine analogue of picoplatin: a new substance from the group of platinum-based chemotherapeutics." Acta Crystallographica Section C Crystal Structure Communications 69, no. 4 (March 6, 2013): 337–39. http://dx.doi.org/10.1107/s0108270113004708.

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A new substance,cis-amminedibromido(2-methylpyridine-κN)platinum(II),cis-[PtBr2(C6H7N)(NH3)], which is a potential platinum-based antineoplastic agent for the treatment of patients with solid tumors, has been synthesized and structurally characterized. There is one molecule in the asymmetric unit and molecules are linkedviatwo symmetry-independent N—H...Br hydrogen bonds into zigzag chains running parallel to thecaxis. C—H...Br hydrogen bonds crosslink these chains to give a layer parallel to (010). N—H...Br hydrogen bonds and π–π stacking interactions between pairs of pyridine rings stack the layers alongb.

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Mountzios, Giannis, Aspasia Soultati, Dimitrios Pectasides, Meletios A. Dimopoulos, and Christos A. Papadimitriou. "Novel Approaches for Concurrent Irradiation in Locally Advanced Cervical Cancer: Platinum Combinations, Non-Platinum-Containing Regimens, and Molecular Targeted Agents." Obstetrics and Gynecology International 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/536765.

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Despite the available prevention and early detection strategies, squamous-cell carcinoma of the uterine cervix is still diagnosed as locally advanced disease in a considerable proportion of patients. As a potent sensitizer of cancer cells, cisplatin has been the “traditional partner” of external beam irradiation in this setting for more than two decades. Induction chemotherapy strategies followed by concurrent chemoradiation or surgery and preoperative concurrent chemoradiation have been recently implemented in clinical trials in an effort to optimize local control and to minimize the risk of distant metastases. In this context, cisplatin has been combined with a number of other potential radiosensitizers, including 5-fluorouracil, capecitabine, and gemcitabine. In patients resistant or intolerant to platinum compounds, numerous non-platinum-containing regimens have been developed, implementing various antimetabolites, taxanes, antineoplastic antibiotics, and topoisomerase II inhibitors. More recently, molecular agents targeting critical pathways in cervical malignant transformation are being assessed in early clinical trials in combination with external-beam irradiation. In the current work, we review the evolving role of cisplatin and other platinum compounds, either alone or in combination regimens, in the context of other potent radiosensitizers. The emerging role of molecular targeted agents, as candidate partners of external beam irradiation, is also discussed.

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Maiese, Eric M., Bruno Émond, Jinan Liu, Marie-Hélène Lafeuille, Patrick Lefebvre, Isabelle Ghelerter, Caterina Wu, Jean Hurteau, and Premal H. Thaker. "Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e18693-e18693. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e18693.

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e18693 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]

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Liu, Jinan, Eric M. Maiese, Bruno Émond, Marie-Hélène Lafeuille, Patrick Lefebvre, Isabelle Ghelerter, Caterina Wu, Jean Hurteau, and Premal H. Thaker. "Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States." Journal of Clinical Oncology 39, no. 28_suppl (October 1, 2021): 291. http://dx.doi.org/10.1200/jco.2020.39.28_suppl.291.

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291 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]

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Toffoli, Giuseppe, Alessandra Viel, Loretta Tumiotto, Patrizio Buttazzi, Gabriella Biscontin, and Mauro Boiocchi. "Sensitivity Pattern of Normal and Ha-Ras Transformed Nih3T3 Fibroblasts to Antineoplastic Drugs." Tumori Journal 75, no. 5 (October 1989): 423–28. http://dx.doi.org/10.1177/030089168907500505.

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Ha-ras-transformed NIH3T3 fibroblasts were compared with the parental cell line to investigate the influence of the Ha-ras oncogene on cellular chemosensitivity to antineoplastic drugs. Four NIH3T3 cell clones independently transformed by the Ha-ras oncogene, activated by mutation or overexpression, were analyzed: 3 clones were obtained by transfection of NIH3T3 cells with a mutation-activated Ha-ras gene and 1 clone by transfection of a large copy number of the normal Ha-ras protooncogene. Chemosensitivity of the transformed clones and of the parental cell line was analyzed when cells were in the same condition of proliferative activity and cell cycle phase distribution. No significant differences in chemosensitivity were observed between transformed and untrans-formed cell lines to doxorubicin, VP-16, cis-platinum or mitomycin C. Therefore, data suggest that activated Ha-ras oncogenes have no role in sensitivity to these antineoplastic agents.

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Szwamel, Katarzyna, Żaneta Dębicka, and Marta Gawlik. "Antineoplastic agents and the use of personal protective equipment: nursing staff awareness." Medical Science Pulse 13, no. 4 (March 31, 2020): 1–20. http://dx.doi.org/10.5604/01.3001.0014.1208.

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Introduction. Along with an increasing number of cancer patients, the need for cytostatic drugs is also increasing. Nursing staff are the largest professional group exposed to the potential dangers of these substances. Aim of the study. Assess the awareness of nursing staff who have direct contact with cytostatic drugs in the use of personal protective equipment (PPE). Material and methods. The research group consisted of 101 nurses routinely exposed to cytostatic drugs. A diagnostic survey and questionnaire technique were used along with the author’s original questionnaire. Results. Of the respondents, 58.42% (n=59) never used protective shoes while dealing with cytostatics, while 53.4% (n=54) never used long-sleeved, waterproof uniforms; 49.50% (n=50) did not apply half masks, and 34.65% (n=35) failed to protect their eyes with protective glasses. The most common cause of not using the protective equipment was identified as lack of time (72; 71.29%). Deficiency of training on protective measures while working with hazardous cytostatics was cited by 37.62% (n=38) as the reason for their behavior, while almost 22% of them claimed that their employer did not provide them with a sufficient amount of protective equipment for individual use. The older, more experienced and higher-educated the staff, the higher awareness among them about the need for using PPE. Conclusions. Higher-educated and more experienced nursing staff should constitute the source of ‘good practices’ and educate younger undergraduate colleagues theoretically and practically. Employers and management staff should provide employees with more training on the correct application of protective measures and increase the intensity of control of the use of personal protective equipment.

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Koepf-Maier, Petra, and Hartmut Koepf. "Non-platinum group metal antitumor agents. History, current status, and perspectives." Chemical Reviews 87, no. 5 (October 1987): 1137–52. http://dx.doi.org/10.1021/cr00081a012.

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Malacrida, Alessio, Cristina Meregalli, Virginia Rodriguez-Menendez, and Gabriella Nicolini. "Chemotherapy-Induced Peripheral Neuropathy and Changes in Cytoskeleton." International Journal of Molecular Sciences 20, no. 9 (May 9, 2019): 2287. http://dx.doi.org/10.3390/ijms20092287.

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Despite the different antineoplastic mechanisms of action, peripheral neurotoxicity induced by all chemotherapy drugs (anti-tubulin agents, platinum compounds, proteasome inhibitors, thalidomide) is associated with neuron morphological changes ascribable to cytoskeleton modifications. The “dying back” degeneration of distal terminals (sensory nerves) of dorsal root ganglia sensory neurons, observed in animal models, in in vitro cultures and biopsies of patients is the most evident hallmark of the perturbation of the cytoskeleton. On the other hand, in highly polarized cells like neurons, the cytoskeleton carries out its role not only in axons but also has a fundamental role in dendrite plasticity and in the organization of soma. In the literature, there are many studies focused on the antineoplastic-induced alteration of microtubule organization (and consequently, fast axonal transport defects) while very few studies have investigated the effect of the different classes of drugs on microfilaments, intermediate filaments and associated proteins. Therefore, in this review, we will focus on: (1) Highlighting the fundamental role of the crosstalk among the three filamentous subsystems and (2) investigating pivotal cytoskeleton-associated proteins.

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Multhaupt, T. P., and S. K. Aggarwal. "Novel Second Generation Platinum Containing Antineoplastic Agents Ssp, Sap, and Poly-Plat and Their Effect on Glucose 6 Phosphate Dehydrogenase (Ec 1.1.1.49) in the Liver and Kidney of Male Wistar Rats." Microscopy and Microanalysis 3, S2 (August 1997): 57–58. http://dx.doi.org/10.1017/s1431927600007170.

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Poly-(trans-l,2-diaminocyclohexane) platinumj-carboxyamylose (Poly-Plat); 5-SuIfosalicylato-trans-(l,2-diaminocyclohexane) platinum (SSP); and 4-Hydroxy-a-sulfonylphenylacetato (trans 1,2-diaminocyclohexane) platinum (II) (SAP) (Andrulis Pharmaceuticals, Bethesda, MD) are three novel second generation platinum containing antineoplastic compounds. Initial studies indicate that these agents are more effective in the treatment of cancer while at the same time less toxic to the organism as a whole than cisplatin (CDDP). The present study was undertaken to examine the effects of these new compounds on glucose-6-phosphate dehydrogenase (G-6-PDH) as compared to CDDP treated and normal kidney and liver tissues.Wistar rats (100-120g) were given intraperitoneal injections of CDDP (9 mg/ kg) and Poly-Plat, SSP and SAP (10 mg/ kg) over a 5 day period. On day 6 the animals were sacrificed and tissues (kidney and liver) were freeze sectioned (7 μm). Sections were incubated in media according to the accepted method specific for the G-6-PDH localization at a pH of 7.46 for 30 min.

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Floyd, Justin D., Duc T. Nguyen, Raymond L. Lobins, Qaiser Bashir, Donald C. Doll, and Michael C. Perry. "Cardiotoxicity of Cancer Therapy." Journal of Clinical Oncology 23, no. 30 (October 20, 2005): 7685–96. http://dx.doi.org/10.1200/jco.2005.08.789.

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Because cancer is a leading cause of mortality in the United States, the number of therapeutic modalities available for the treatment of neoplastic processes has increased. This has resulted in a large number of patients being exposed to a wide variety of cancer therapy. Historically, it has been well recognized that antineoplastic agents may have adverse effects on multiple organs and normal tissues. The most commonly associated toxicities occur in tissues composed of rapidly dividing cells and may spontaneously reverse with minimal long-term toxicity. However, the myocardium consists of cells that have limited regenerative capability, which may render the heart susceptible to permanent or transient adverse effects from chemotherapeutic agents. Such toxicity encompasses a heterogeneous group of disorders, ranging from relatively benign arrhythmias to potentially lethal conditions such as myocardial ischemia/infarction and cardiomyopathy. In some instances, the pathogenesis of these toxic effects has been elucidated, whereas in others the precise etiology remains unknown. We review herein the various syndromes of cardiac toxicity that are reported to be associated with antineoplastic agents and discuss their putative mechanisms and treatment.

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Vijayakumar, Jayanthi, Jeffrey Jackson, Kwang W. Ahn, and Parameswaran N. Hari. "Meta-Analysis of Pharmacotherapy Vs. Observation for Management of Smoldering Multiple Myeloma." Blood 124, no. 21 (December 6, 2014): 4771. http://dx.doi.org/10.1182/blood.v124.21.4771.4771.

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Abstract Introduction: Asymptomatic or smoldering multiple myeloma (SMM) is usually 10-15% of all patients with multiple myeloma. Currently, national guidelines do not recommend early treatment of SMM though the majority of patients progress to active disease over time. Multiple trials have been conducted to evaluate implications of early therapy for SMM. Some of these trials, most notably, Mateos et al. (N Engl J Med 2013; 369:438-447) have shown benefit for treating SMM. However, there is lack of consensus as to whether early treatment of SMM prior to symptomatic disease progression is superior to observation alone. Hence we conducted a meta- analysis to determine if observation or treatment is superior in the management of SMM. Methods: We searched MEDLINE, the Cochrane database and hand-search of articles to identify 12 clinical trials which allocated SMM patients to treatment. Study quality was assessed using the Cochrane risk of Bias tool. Our main outcomes were progression free survival (PFS) and overall survival (OS). Sub-analysis examined the difference in treatment with antineoplastic agent (C), bisphosphonates (B), or their combination (CB). Data were pooled using a random effects meta-analysis using STATA (College Station Texas, V13.2). Results: Among the 12 trials, 4 trials were excluded due lack of survival curves for OS, PFS, TTP. Characteristics of the 8 included clinical trials are given in Table 1. Participants treated for early SMM had reduced mortality (HR: 0.64, 95% CI 0.4-1.0) and better PFS (HR=0.83, 95% CI, 0.64-1.07) compared to the observation group. In subgroup analysis, patients treated with either antineoplastic agents or the combination of antineoplastic agents and bisphosphonate had a better OS and PFS, whereas therapy with only bisphosphonate did not impact OS or PFS (Figures 1, 2). Conclusion: We conclude that antineoplastic treatment or a combination of antineoplastic agents and bisphosphonates is better than observation in improving overall survival in SMM patients. A similar trend is seen with PFS. This conclusion merits caution given the limited data available and the differences in the agents used for therapy. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Pelletier, Karyne, Marko Škrtić, and Abhijat Kitchlu. "Cancer therapy-induced hyponatremia: A case-illustrated review." Journal of Onco-Nephrology 5, no. 1 (February 2021): 70–78. http://dx.doi.org/10.1177/23993693211002216.

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Hyponatremia is the most common electrolyte disorder in patients with cancer and is associated with significant morbidity and mortality. Innovation in cancer therapies has led to substantial improvement in cancer outcomes, but also to new therapy-related toxicities, including electrolyte disturbance. Improvement in clinicians understanding of hyponatremia may mitigate adverse outcomes and improve quality of life in cancer patients. In this case-illustrated review, we discuss the mechanisms underlying drug-induced hyponatremia both in “classical” antineoplastic drugs and novel cancer therapies. Via these clinical cases, we describe hyponatremia caused by conventional chemotherapies (e.g. platinum compounds, vinca alkaloid, and alkylating agents) as well as hyponatremia related to tyrosine kinase inhibitors and other targeted therapies. We also focus on checkpoint inhibitors-induced hyponatremia, as these agents are increasingly used for a wide variety of malignancies. Lastly, we summarize therapy-related hyponatremia among recipients of newer treatments for multiple myeloma.

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Haque, Ashanul, Md Ataur Rahman, Md Serajul Haque Faizi, and Muhammad S. Khan. "Next Generation Antineoplastic Agents: A Review on Structurally Modified Vinblastine (VBL) Analogues." Current Medicinal Chemistry 25, no. 14 (May 7, 2018): 1650–62. http://dx.doi.org/10.2174/0929867324666170502123639.

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Background: Throughout the history of human civilizations, cancer has been a major health problem. Despite the advancements made by modern medical sciences, complete treatment or removal of cancerous cells is still a challenging task. Vinblastine, an alkaloid obtained from Catharanthus roseus (L.) G. Don is one of the prominent antineoplastic agents that is being clinically used. To improve the biological potential and reduce sideeffects of this structurally complex molecule, several related analogues have been reported. The present article reviews recently reported structurally modified vinblastine analogues and its impact on biological activity. Methods: We carried out a comprehensive database search on recently reported vinblastine analogues. Both upper (catharanthine) and lower (vindoline) structural units have been considered. The role of functional group modification on anticancer activities has been discussed. In addition, formulations based on vinblastine being considered by NIH, USA for different types of cancers have also been discussed. Results: Around fifty papers were included in the review, including computational and experimental ones. These papers were analysed to discuss the mechanism of action of the parent vinblastine molecule and their analogues. The importance of each functionalities on its anticancer activity have been discussed. This reviewed identified the potential sites of vinblastine core where modification led to improved anticancer activity. Furthermore, several new formulations have also been discussed which are under different phases of clinical trial. Conclusion: The present article highlights the importance of vinblastine in cancer chemotherapy. Literature survey confirms that it is now possible to synthesize new molecules with activity in picomolar range. Not only the periphery of the molecule, the core structure of this magical molecule can be modified to achieve next generation antineoplastic agents.

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Momekov, Georgi, Adriana Bakalova, and Margarita Karaivanova. "Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity." Current Medicinal Chemistry 12, no. 19 (September 1, 2005): 2177–91. http://dx.doi.org/10.2174/0929867054864877.

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Ruggiero, Antonio, Giovanna Trombatore, Silvia Triarico, Michele Antonio Capozza, Paola Coccia, Giorgio Attina, Stefano Mastrangelo, and Palma Maurizi. "Cisplatin Toxicity in Children with Malignancy." Biomedical and Pharmacology Journal 12, no. 04 (December 28, 2019): 1603–11. http://dx.doi.org/10.13005/bpj/1791.

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Platinum’ derivates are antineoplastic agents widely adopted for their efficacy for the treatment of many pediatric cancers. The use of cisplatin has positively influenced the results of the cure of different childhood malignancies. However, cisplatin-based treatments are limited by the risk of severe and progressive toxicities, such as oto- or nephrotoxicity, that can be more serious in very young children expecially when high cumulative doses and/or radiotherapy is administered. A correct knowledge of the cisplatin’ pharmacological features might be of interest for clinicians in order to manage its potential toxicities. Based on the positive trend in the cure of children with cancer, it is crucial that all children receiving cisplatin-based chemotherapy have and appropriate and long-term follow-up to improve their quality of life.

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Maulana, Ilham Maulana Ilham, Peter Loennecke Peter Loennecke, and Evamarie Hey-Hawkins Evamarie Hawkins. "Platinum Metal Complexes of Carbaboranylphophines: Potential Anti Cancer Agents." Indonesian Journal of Cancer Chemoprevention 1, no. 1 (February 28, 2010): 1. http://dx.doi.org/10.14499/indonesianjcanchemoprev1iss1pp1-11.

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Polyhedral heteroboranes in particular dicarba-closo-dodecaboranes(12) and their organic derivatives have been the subject of intense research for over 40 years due to their unique chemical and physical properties. The initial attraction to dicarba-closo-dodecaboranes(12) In the medicinal chemistry research, was a result of their high boron content and stability to catabolism, which are important criteria for cancer therapy, such as BNCT (boron neutron capture therapy) agents. The coordination compounds of the platinum group metals have also received large interest for their potential application as chemotherapeutic agents, since cis-diamminedichloroplatinum(II), cisplatin, has been reported to have capability as tumor inhibitor. Hence, applications can be envisioned for related cis platinum complexes. Complex of cis-rac-[PtCl2{1,2-(PRCl)2C2B10H10}] (R=Ph, tBu, NEt2, NPh2) have been synthesized by employing known carbaborane based phosphine ligands of clorophoshino-closo-dodecaborane , with complex of cis-[PtCl2(COD)] (COD = 1,5-cyclooctadiene) in an N2-atmosphere. The obtained complexes possess expected structure configuration, namely cis-rac. The characterization of the complex has been carried out using 1H, 31P, 13C and 11B-NMR (Nuclear Magnetic Resonance), X-ray of single crystals, elemental analysis, IR (infra red) and mass spectroscopy (MS). The 31P{1H} NMR spectra of all the platinum complexes distinctly show the typical platinum satellites which are attributed to 31P-195Pt-coupling, in which the 31P{1H} NMR spectrum exhibits three lines with an intensity ratio of ca.1:4:1. The structure of the platinum complexes consists of a slightly distorted square-planar coordination sphere, in which the platinum atom is bonded to two chlorides and two phosphorus atoms of the chelating carbaboranylphosphine. Thus the platinum atoms exhibit the coordination number four, which is preferred in platinum(II) complexes.Keywords: Platinum complexes, phosphine ligand, carbaborane

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Visacri, Marília Berlofa, Cinthia Madeira de Souza, Rafaela Pimentel, Cristina Rosa Barbosa, Catarina Miyako Shibata Sato, Silvia Granja, Mécia de Marialva, Carmen Silvia Passos Lima, Priscila Gava Mazzola, and Patrícia Moriel. "Pharmacovigilance in oncology: pattern of spontaneous notifications, incidence of adverse drug reactions and under-reporting." Brazilian Journal of Pharmaceutical Sciences 50, no. 2 (April 2014): 411–22. http://dx.doi.org/10.1590/s1984-82502014000200021.

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The high toxicity and narrow therapeutic window of antineoplastic agents makes pharmacovigilance studies essential in oncology. The objectives of the current study were to analyze the pattern of spontaneous notifications of adverse drug reactions (ADRs) in oncology patients and to analyze the incidence of ADRs reported by outpatients on antineoplastic treatment in a tertiary care teaching hospital. To compose the pattern of ADR, the notification forms of reactions in oncology patients in 2010 were reviewed, and the reactions were classified based on the drug involved, mechanism, causality, and severity. To evaluate the incidence of reactions, a questionnaire at the time of chemotherapy was included, and the severity was classified based on the Common Terminology Criteria. The profiles of the 10 responses reported to the Pharmacovigilance Sector were type B, severe, possible, and they were primarily related to platinum compounds and taxanes. When the incidence of reactions was analyzed, it was observed that nausea, alopecia, fatigue, diarrhea, and taste disturbance were the most frequently reported reactions by oncology patients, and the grade 3 and 4 reactions were not reported. Based on this analysis, it is proposed that health professionals should be trained regarding notifications and clinical pharmacists should increasingly be brought on board to reduce under-reporting of ADRs.

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Kulyova, Svetlana A., Tatiana Yu Semiglazova, Daria A. Zvyagintseva, Margarita B. Belogurova, Svetlana V. Ivanova, and Irina V. Okisheva. "Cardiovascular complications of antineoplastic therapy in children." Pediatrician (St. Petersburg) 8, no. 3 (May 15, 2017): 130–41. http://dx.doi.org/10.17816/ped83130-141.

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The improvement of long-term survival in children with malignant tumors is noted in the last five decades. Serious late consequences of the applied therapy including early death, the second tumors, different organ dysfunctions (heart, gonads, liver, lungs) began to come to light with increase in number of cured and follow-up. The article discusses the emergence of cardiotoxicity in children treated with cytostatic and radiation therapy for malignant tumors. Particular attention is paid to the influence of anthracycline antibiotics on the state of the heart muscle. Anthracycline and similar medicines - doxorubicin, rubomycin, idarubicin, mitoxantrone - are an important component of most regimen of chemotherapy in children. Briefly describes the history of the application of this group of drugs in oncology and the study of their effects on heart function. The attention to the pathogenesis of anthracycline cardiotoxicity risk factors for its development, display options, how to identify and mitigate. We describe the clinical manifestations of early and late cardiotoxicity arising after the application of antitumor antibiotics anthracyclines. The article defines the role of chemotherapeutic agents other groups in the development and worsening cardiotoxicity. No less important role in the development of long-term effects of the heart and blood vessels plays radiotherapy. The paper paid attention to cardiovascular dysfunctions that arise in different periods of observation after irradiation of the mediastinum. Finally, recommendations for practitioners on screening, monitoring and treatment of identified diseases of the cardiovascular system in patients cured of childhood malignancies are presented.

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Długosz-Pokorska, Angelika, Joanna Drogosz, Marlena Pięta, Tomasz Janecki, Urszula Krajewska, Marek Mirowski, and Anna Janecka. "New Uracil Analogs with Exocyclic Methylidene Group as Potential Anticancer Agents." Anti-Cancer Agents in Medicinal Chemistry 20, no. 3 (April 24, 2020): 359–68. http://dx.doi.org/10.2174/1871520619666191211104128.

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Background: Hybrid molecules combining uracil skeleton with methylidene exo-cyclic group were designed in the search for novel anticancer drug candidates. Objective: Two series of racemic 5-methylidenedihydrouracils, either 1,3-disubstituted or 1,3,6-trisubstituted were synthesized and tested for their possible cytotoxic activity against two cancer cell lines (HL-60 and MCF-7) and two healthy cell lines (HUVEC and MCF-10A). The most cytotoxic analogs were re-synthesized as pure enantiomers. The analog designated as U-332 [(R)-3-(4-bromophenyl)-1-ethyl-5-methylidene-6-phenyldihydrouracil], which had a very low IC50 value in HL-60 cell line (0.77μM) and was the most selective towards cancer cells was chosen for further experiments on HL-60 cell line, in order to determine the possible mechanism involved in its antineoplastic action. Methods: Cytotoxic activities of compound was assessed by the MTT assay. In order to explore the mechanism of U-332 activity, we performed quantitative real-time PCR analysis of p53 and p21 genes. Apoptosis, cell proliferation and DNA damage in HL-60 cells were determined using the flow cytometry. The ability of U-332 to determine GADD45ɑ protein level in HL-60 cells incubated with U-332 was analyzed by ELISA test. Results: U-332 was shown to generate excessive DNA damage (70% of the cell population), leading to p53 activation, resulting in p21 down-regulation and a significant increase of GADD45α protein, responsible for the cell cycle arrest in G2/M phase. Conclusion: U-332 can be used as a potential lead compound in the further development of novel uracil analogs as anticancer agents.

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Li, Zhen-Yu, Zhen Zhang, Xiao-Zhong Cao, Yun Feng, and Sha-Sha Ren. "Platinum-based neoadjuvant chemotherapy for triple-negative breast cancer: a systematic review and meta-analysis." Journal of International Medical Research 48, no. 10 (October 2020): 030006052096434. http://dx.doi.org/10.1177/0300060520964340.

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Background Triple-negative breast cancer (TNBC) is associated with higher aggressiveness and mortality than hormone-positive breast cancer because of the lack of approved therapeutic targets. Patients with TNBC who attain a pathological complete response (pCR) after neoadjuvant chemotherapy have improved survival. Platinum-based agents show promising activity in TNBC; however, their use remains controversial. We conducted a meta-analysis to assess the role of platinum-based agents in neoadjuvant chemotherapy in patients with TNBC. Methods We performed an extensive literature search of the Pubmed, Embase, and Cochrane databases. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) for the identified studies. Results Eight randomized controlled trials with 1345 patients were included in the analysis. The addition of platinum-based agents improved pCR compared with neoadjuvant therapy based on anthracyclines, cyclophosphamide, taxanes, and fluorouracil (49.1% vs. 35.9%; OR: 1.87, 95% CI: 1.23–2.86). Hematological adverse events were similar in both groups, except for more thrombocytopenia in the platinum-based group (OR: 7.96, 95% CI: 3.18–19.93). Conclusion The addition of platinum-based agents to neoadjuvant chemotherapy improved pCR rates in patients with TNBC, with a slight increase in hematological toxicities. Platinum-based agents might thus be an accessible and economically viable option in patients with TNBC.

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Jurisevic, Milena, Gordana Radosavljevic, Aleksandar Arsenijevic, Marija Milovanovic, Nevena Gajovic, Dragana Djordjevic, Jelena Milovanovic, et al. "Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents." Serbian Journal of Experimental and Clinical Research 17, no. 4 (December 1, 2016): 285–96. http://dx.doi.org/10.1515/sjecr-2016-0042.

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Abstract The design of platinum based drugs is not a new field of interest. Platinum complexes are widely used as anticancer agents and currently, approximately 30 platinum(II) and platinum(IV) entered into some of the phases of clinical trials. A special place in today’s research belongs to platinum complexes with diammine ligands. A large number of edda (ethylenediamine- N, N’-diacetate)-type ligands and their corresponding metal complexes has been successfully synthesized. This article summarizes recent progress in research on edda-type-platinum complexes. Some of these agents achieves better effect compared to the gold standard (cisplatin). It has been shown that there is a possible relationship between the length of the ligand ester group carbon chain and its cytotoxic effect. In most cases the longer the ester chain is the greater is the antitumor activity. Of particular interest are the noticeable effects of some new platinum compound with edda-type ligand on cell lines that are known to have a high level of cisplatin-resistance. Exanimate complexes appear to have a different mode of mechanism of action compared with cisplatin which includes apoptotic and necrotic cell death. There are indications that further investigations of these compounds may be very useful in overcoming the problems associated global cancer statistic.

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Batista de Carvalho, A. L. M., S. F. Parker, L. A. E. Batista de Carvalho, and M. P. M. Marques. "Novel platinum-based anticancer drug: a complete vibrational study." Acta Crystallographica Section C Structural Chemistry 74, no. 5 (April 23, 2018): 628–34. http://dx.doi.org/10.1107/s2053229618005843.

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The introduction of cisplatin to oncology, in the 1970s, marked the onset of the search for novel and improved metal-based anticancer drugs. Polynuclear PtII and PdII complexes with linear alkylamines as bridging ligands are a class of potential antineoplastic agents that have shown promising cytotoxicity against low-prognosis human cancers, such as metastatic breast adenocarcinoma and osteosarcoma. The present study reports an analysis of [μ-N,N′-bis(3-aminopropyl)butane-1,4-diamine-κ4 N,N′:N′′,N′′′]bis[dichloridoplatinum(II)], [Pt2Cl4(C10H26N4)], denoted Pt2Spm (Spm is spermine), by vibrational spectroscopy coupled to theoretical calculations. Within the latter, the Density Functional Theory (DFT – mPW1PW/6-31G*) and Effective Core Potential (ECP – LANL2DZ) approaches were used, in order to ensure the most accurate representation of the molecule and achieve a maximum agreement with the experimental data. The solid-state geometry of Pt2Spm corresponds to Ci symmetry, displaying 132 vibrational modes. A complete assignment of the experimental vibrational profile of the system was attained through the combined application of complementary Raman, FT–IR and Inelastic Neutron Scattering (INS) techniques. INS allowed an unequivocal identification of the CH2 and NH2 rocking modes, not clearly detected by the optical techniques, while Raman measurements led to a clear discrimination of the Pt—N stretching frequencies from the two distinct Pt—N moieties within the chelate. The metal-to-metal distances calculated for the molecule under study were found to allow the establishment of effective inter- and intrastrand crosslinks with DNA. These results will hopefully help to clarify the mode of action of the compound, at the molecular level, contributing to the development of improved cisplatin-like chemotherapeutic drugs having a higher efficacy and specificity coupled to lower acquired resistance and deleterious side effects.

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Aldubayan, Maha A., Rehab M. Elgharabawy, Amira S. Ahmed, and Ehab Tousson. "Antineoplastic Activity and Curative Role of Avenanthramides against the Growth of Ehrlich Solid Tumors in Mice." Oxidative Medicine and Cellular Longevity 2019 (January 13, 2019): 1–12. http://dx.doi.org/10.1155/2019/5162687.

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Interest is growing in finding natural sources of effective antitumor agents that generate fewer side effects than conventional chemotherapeutic drugs. Avenanthramides (Avns) are such compounds; these phenolic molecules naturally occur in oats and have antioxidant, anti-inflammatory, and antiproliferative effects making them worthy of further research. The aim of this study is to characterise Avns’ curative ability and antineoplastic activity on solid-form Ehrlich tumors. For the study, 75 female mice were randomly and equally allocated to five groups (group 1-control, group 2-DMSO, group 3-positive control receiving Avns, group 4-mice with Ehrlich solid tumor, and group 5-Ehrlich solid tumor treated with Avns). Mice with Ehrlich solid tumors exhibit increased tumor volume; elevated expression of AFP, ALT, AST, Bcl2, CEA, cholesterol, creatinine, urea, MDA, PCNA, potassium, triglycerides, TNF-α, and NF-κB; and a concomitant decline in catalase, GSH, P53, and SOD. In the mice with Ehrlich tumors who received Avns, there appeared to be improvement in NF-κB TNF-α, tumor markers (AFP and CEA), electrolytes, liver and kidney function enzymes, and lipid profiles; reduced MDA level; improved antioxidant parameters; normalised liver protein, P53, and PCNA; and reduced Bcl2 expression. Pathological examination of tumor lesions also indicated improvement. These results suggest that Avns exhibit antineoplastic activity and possess antioxidant properties that enhance the antioxidant defence system, thus reducing the oxidative stress caused by Ehrlich solid tumors.

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Jordan, Berit, Franziska Jahn, Sandra Sauer, and Karin Jordan. "Prevention and Management of Chemotherapy-Induced Polyneuropathy." Breast Care 14, no. 2 (2019): 79–84. http://dx.doi.org/10.1159/000499599.

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Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe and common side effect caused by a variety of antineoplastic agents. Approximately 30–40% of patients treated with agents such as taxanes, vinca alkaloids, or platinum derivatives will develop CIPN. CIPN presents predominantly as a sensory axonal neuro(no)pathy with occasional motor and autonomic dysfunction exhibiting considerable variability of clinical symptoms ranging from mild tingling sensation to severe neuropathic pain. Typical symptoms include numbness (“minus symptom”), weakness, and abnormal gait as well as paresthesia and pain (“positive symptoms”). As CIPN symptoms potentially lead to long-term morbidity and can even aggravate after cessation of therapy, patients’ quality of life can be tremendously affected. In view of improved breast cancer survival outcomes, the late effects of CIPN are an unmet need in these patients. Therefore, early detection and assessment of first symptoms is important to effectively prevent severe CIPN. Therapeutic options for patients with CIPN are still limited, and pharmacological treatment focuses primarily on reduction or relief of neuropathic pain. CIPN is usually acutely managed by dose reduction or discontinuation of causative chemotherapy, potentially compromising treatment outcome. Currently, there is no causative proven therapy for the prevention of CIPN.

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Vermorken, J. B. "The role of anthracyclines in second-line therapy of ovarian cancer." International Journal of Gynecologic Cancer 13, Suppl 2 (2003): 178–84. http://dx.doi.org/10.1136/ijgc-00009577-200311001-00009.

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Anthracyclines (ANTs) have been in clinical practice since the 1960s and represent one of the most commonly used classes of anticancer drugs. In the 1990s, meta-analyses showed a favorable impact of doxorubicin (DOX/A) on the survival of patients with advanced ovarian cancer, when it was combined with cyclophosphamide and cisplatin (CAP) and compared to CP alone. With the acceptance of paclitaxel-carboplatin (TCb) as the new reference arm for first-line treatment, testing the addition of ANTs to TCb seems a logic next step. Trials presently testing this, make use of either epirubicin (EPI) or pegylated liposomal doxorubicin (PLD: Doxil®/Caelyx®). These are the two most favorable ANTs, based on data obtained with various ANTs in ovarian cancer failing platinum-based chemotherapy. EPI has not been evaluated in direct comparison with other antineoplastic agents. PLD has been compared with both paclitaxel and topotecan. No difference in efficacy parameters could be observed, but the toxicity profile of PLD scored favorably against those of the comparator in both trials, despite the fact that palmar-plantar erythrodysesthesia can be troublesome, and sometimes lead to treatment discontinuation. Data from four randomized trials evaluating the role of ANT combinations in patients with relapsed ovarian cancer suggest that the addition of EPI or DOX to paclitaxel does not lead to better outcomes in patients with platinum-refractory or resistant disease. In platinum-sensitive disease, any benefit of EPI-platinum or DOX-platinum combinations over platinum alone is uncertain. There are no randomized trials with PLD combinations in the second-line setting. It is concluded that both EPI and PLD can be recommended as a reasonable single-agent treatment option for relapsed patients, with a preference for PLD taking into account its more favorable toxicity profile.

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Momekov, Georgi, Dilyan Ferdinandov, Spiro Konstantinov, Sonja Arpadjan, Daniela Tsekova, Galina Gencheva, Panayot R. Bontchev, and Margarita Karaivanova. "In Vitro Evaluation of a Stable Monomeric Gold(II) Complex with Hematoporphyrin IX: Cytotoxicity against Tumor and Kidney Cells, Cellular Accumulation, and Induction of Apoptosis." Bioinorganic Chemistry and Applications 2008 (2008): 1–8. http://dx.doi.org/10.1155/2008/367471.

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The antineoplastic potential of a stable monomeric Au(II) complex with hematoporphyrin IX (Hp), namely [Au(II)Hp-2H.(H2O)2], was investigated in a panel of tumor cell lines. The complex exhibits strong cytotoxicity, whereby the leukaemia- and lymphoma-derived cell lines are more sensitive, withIC50values comparable to those of the reference anticancer drug cisplatin. In contrast, the solid tumor models are more sensitive to the platinum drug. A comparative assessment of both agents against the human kidney cell line 293T has shown that [Au(II)Hp-2H.(H2O)2] is less cytotoxic. The gold complex induces oligonucleosomal DNA fragmentation in tumour cells following 24-hour treatment and hence its cytotoxic effect is at least partly mediated by induction of apoptotic cell death. A prominent intracellular gold accumulation was detected after treating tumor cells with [Au(II)Hp-2H.(H2O)2] which shows that its putative pharmacological targets are readily accessible after a short incubation period.

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Yoo, Jeongsoo, and Youngkyu Do. "Synthesis of stable platinum complexes containing carborane in a carrier group for potential BNCT agents." Dalton Transactions, no. 25 (2009): 4978. http://dx.doi.org/10.1039/b823193a.

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Das, Swagatika, H. Inci Gul, Umashankar Das, Jan Balzarini, Stephen G. Dimmock, and Jonathan R. Dimmock. "Novel Conjugated Unsaturated Ketones with Submicromolar Potencies Towards some Leukemic and Colon Cancer Cells." Medicinal Chemistry 15, no. 4 (May 20, 2019): 430–38. http://dx.doi.org/10.2174/1573406414666181015142633.

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Background: Cancer continues to be the major health burden worldwide. There is an urgent need for the development of novel antineoplastic compounds to treat this devastating condition. Various alkylating anticancer drugs have been employed in the clinic for treating cancers. Unsaturated conjugated ketones are a group of alkylators which are of significant interest as potent antineoplastic agents. Objective: The goal of this study is to discover unsaturated conjugated ketones which are novel potent cytotoxins displaying growth-inhibitory properties towards neoplasms and also to serve as cytotoxic warheads in drug development. Methods: A variety of 3,5-bis (benzylidene)-4-piperidones 2a-n were synthesized and evaluated against a number of neoplastic cell lines. The short-term neurotoxicity of 2a-k, n was evaluated in mice by i.p. administration using doses level of 30, 100 and 300 mg/kg. Statistical correlations for determining structure-activity relationships were performed using an SPSS software. Results: A number of compounds display cytotoxic potencies in the region of 10-7 to 10-8 M and some of the structural features contributing to the cytotoxicity were identified. Compounds 2a-d, 2h demonstrated substantially higher cytotoxic potencies compared to melphalan and 5- fluorouracil against a panel of leukemic and colon cancer cell lines. These lead cytotoxins comply with drug-likeness properties. In general, the antineoplastics 2 are well tolerated in mice using a short-term neurotoxicity screening. Conclusion: In general, this group of compounds comprises excellent cytotoxic agents, which warrant their further development as cytotoxic warheads.

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Fracasso, Paula M., John A. Blessing, Mark A. Morgan, Anil K. Sood, and James S. Hoffman. "Phase II Study of Oxaliplatin in Platinum-Resistant and Refractory Ovarian Cancer: A Gynecologic Group Study." Journal of Clinical Oncology 21, no. 15 (August 1, 2003): 2856–59. http://dx.doi.org/10.1200/jco.2003.03.077.

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Purpose: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with platinum-resistant or refractory epithelial ovarian carcinoma. Materials and Methods: Eligible patients were to receive oxaliplatin 130 mg/m2 intravenously over 2 hours, every 21 days, until progression of disease or adverse effects prohibited further therapy. Results: Of 25 patients entered onto the study, 23 were eligible and assessable. There were no patients with complete response. One patient (4.3%) achieved a partial response, with a response duration of 6.4 months. Nine patients (39.1%) experienced stable disease, with a median duration of 5.6+ months (range, 1.8 to 13.1months). The most frequently reported drug-related toxicities were hematologic, gastrointestinal, and neurologic. Conclusion: Oxaliplatin as a single agent has minimal activity in patients with platinum-resistant or refractory ovarian cancer at the dosage and schedule tested. However, future studies of oxaliplatin combined with other active agents in women with platinum-naïve or platinum-sensitive epithelial ovarian carcinoma may be indicated.

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Möller, Angela, and Gerd Meyer. "The ammonium ion and the ammine ligand as internal reducing agents for platinum-group-metal complexes." Thermochimica Acta 210 (November 1992): 147–50. http://dx.doi.org/10.1016/0040-6031(92)80284-4.

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Chalupczok, Sebastian, Peter Kurzweil, and Helmut Hartmann. "Impact of Various Acids and Bases on the Voltammetric Response of Platinum Group Metal Oxides." International Journal of Electrochemistry 2018 (2018): 1–6. http://dx.doi.org/10.1155/2018/1697956.

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The voltammetric response of platinum metal oxides is discussed with respect to novel pH sensors combining both miniaturization and stability. For practical applications in solutions of any kind, for example, in tap water and in domestic sewage, various interferences must be considered, such as chloride and reducing agents. This work clarifies the voltammetric behavior of RuO2 electrodes in solutions of different pH values and ionic strengths.

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Hochster, Howard, Elizabeth R. Plimack, Carolyn D. Runowicz, James Speyer, Robert C. Wallach, Joan Sorich, John Mandeli, Scott Wadler, John Wright, and Franco M. Muggia. "Biweekly 72-Hour 9-Aminocamptothecin Infusion As Second-Line Therapy for Ovarian Carcinoma: Phase II Study of the New York Gynecologic Oncology Group and the Eastern Cooperative Oncology Group." Journal of Clinical Oncology 22, no. 1 (January 1, 2004): 120–26. http://dx.doi.org/10.1200/jco.2004.03.016.

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Purpose To determine the antitumor activity of the novel topoisomerase I inhibitor 9-aminocamptothecin (9-AC) given over 72 hours every 2 weeks in patients with ovarian carcinoma previously treated with one platinum-containing regimen. Patients and Methods Patients with ovarian carcinoma who received one prior platinum-containing regimen were eligible. Patients were stratified based on whether their disease was measurable, or nonmeasurable but assessable. 9-AC 35 μg/m2/h was administered by continuous infusion for 72 hours every 2 weeks via ambulatory pump. Results Sixty patients were entered, 32 with measurable and 28 with nonmeasurable but assessable disease. Ten (16.7%) of 60 patients responded (95% CI, 7.2% to 26.1%), with four complete responses and six partial remissions. The response rate for patients with measurable and nonmeasurable but assessable disease was 22% (95% CI, 7.6% to 36.2%) and 10.7% (95% CI, 2.3% to 28.2%), respectively. None of the responders were platinum-resistant. Nineteen patients (32%) had stable disease. The major toxicities were hematologic, with 25% of patients having grade 3 and 35% having grade 4 neutropenia, including five episodes of febrile neutropenia, 17% having grade 3 to 4 thrombocytopenia, and 27% having grade 3 to 4 anemia. Nonhematologic toxicity included grade 3 to 4 nausea (27%) and grade 3 to 4 vomiting (12%). Conclusion This phase II multicenter trial of biweekly 72 hour 9-AC infusion as second-line therapy for ovarian cancer demonstrates comparable activity to standard approved agents in patients with both measurable and nonmeasurable but assessable disease. Toxicity consists mainly of moderate but controllable myelosuppression. Further studies combining 9-AC with other agents active in ovarian cancer for use as second-line therapy are warranted.

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Takano, M., T. Sugiyama, N. Yaegashi, M. Sakuma, M. Suzuki, Y. Saga, K. Kuzuya, et al. "Low response rate of second-line chemotherapy for recurrent or refractory clear cell carcinoma of the ovary: a retrospective Japan Clear Cell Carcinoma Study." International Journal of Gynecologic Cancer 18, no. 5 (2008): 937–42. http://dx.doi.org/10.1111/j.1525-1438.2007.01158.x.

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Clear cell carcinoma (CCC) of the ovary has been recognized to show resistance to anticancer agents in the first-line chemotherapy. Our aim was to evaluate the effect of second-line chemotherapy in a retrospective study. A total of 75 patients diagnosed with CCC and treated between 1992 and 2002 in collaborating hospitals were reviewed. Criteria for the patients' enrollment were 1) diagnosis of pure-type CCC at the initial operation, 2) treatment after one systemic postoperative chemotherapy, 3) measurable recurrent or refractory tumor, 4) at least two cycles of second-line chemotherapy and assessable for the response, and 5) adequate clinical information. Regimens of first-line chemotherapy were conventional platinum-based therapy in 33 cases, paclitaxel plus platinum in 24 cases, irinotecan plus platinum in 9 cases, and irinotecan plus mitomycin C in 7 cases. Treatment-free periods were more than 6 months in 24 cases (group A) and less than 6 months in 51 cases (group B). In group A, response was observed in two cases (8%): one with conventional platinum therapy and another with irinotecan plus platinum. In group B, three cases (6%) responded: two with platinum plus etoposide and one case with irinotecan plus platinum. Median overall survival was 16 months in group A and 7 months in group B (P= 0.04). These findings suggest recurrent or resistant CCC is extremely chemoresistant, and there is only small benefit of long treatment-free period in CCC patients. Another strategy including molecular-targeting therapy is warranted for the treatment of recurrent or refractory CCC.

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Journal articles on the topic 'Platinum group. Antineoplastic agents'

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