Academic literature on the topic '111205 Chemotherapy'

Abstract CD19-specific CAR-T cells are highly successful against B-cell non-Hodgkin lymphomas and acute lymphoblastic leukemia but targets for other lymphoproliferative disorders have been harder to define. Almost all HL and some NHL express the CD30 antigen both at diagnosis and relapse, and monoclonal antibodies (mAb) targeting CD30 (e.g. brentuximab) produce objective antitumor responses. However, mAb have limited bio-distribution and their benefits may be short-lived. We therefore expressed the antigen binding domain of a CD30 mAb as part of a chimeric antigen receptor (CAR) on T cells, coupled to the CD28 and z chain endodomains. We have previously published results of a phase 1 study of activated autologous CD30.CAR-T cells (CD30.CARTs) infused in patients with relapsed/refractory CD30+ HL or NHL without preceding chemotherapy (Ramos et al., J Clin Invest 2017). Of 6 patients with relapsed active HL, 1 entered complete remission (CR) that has lasted more than 3 years, and 3 had transient stable disease. No significant toxicities were observed. In order to boost the in vivo expansion and potentially the efficacy of these CD30.CARTs we are now infusing them after lymphodepleting chemotherapy (RELY-30, NCT02917083). We report here preliminary results of that study, which suggest a substantial improvement in efficacy. We have manufactured CD30.CARTs for 15 patients using retroviral transduction. Culture duration was 15±3 days, with a final transduction efficiency of 97.6%±1.8%. The cell products comprised >98% T cells, with a majority of them being effector T cells (CD45RO+ 95.5%±6.0%). 51Cr-release cytotoxicity assays confirmed that patients' CD30.CARTs lysed a CD30+ tumor line, HDLM-2 (45.9%±15.4% killing at a 20:1 effector:target ratio), with negligible effects on CD30− target cells (<5% killing). During cell manufacture, 1 patient became ineligible due to rapid worsening of his performance status and liver function. Five patients are awaiting treatment on trial. Nine relapsed/refractory HL patients have received CD30.CARTs under the RELY-30 trial. Six of these had relapsed or progressed after treatment with brentuximab. Three patients have been treated on dose level (DL) 1 (2×107 CD30.CAR+ T cells/m2) and 6 patients on DL2 (1×108). All patients received lymphodepleting chemotherapy (cyclophosphamide 500 mg/m2 and fludarabine 30 mg/m2 daily for 3 days) before CART infusion. CART infusions were associated with grade 1 cytokine release syndrome in 4 of the patients, and a transient maculopapular rash in 6 of the patients, starting approximately one week after administration. The molecular signal from CARTs, assessed by Q-PCR in peripheral blood, peaked at 1-2 weeks following infusion, but dropped progressively after 4 weeks and decreased to near the limit of detection level by 6 months post infusion. The signal level was dose dependent, with a peak average of 19,371 copies/mg DNA in patients treated on DL2 versus 7,132 copies/mg for DL1. Compared to patients who received the same CART dose but who were not given lymphodepleting chemotherapy in our previous trial, expansion levels were 45 and 119-fold higher, respectively. Eight patients have been evaluated at 6 weeks after infusion. Six have had a CR lasting from >6 weeks to >6 months, while 2 patients had disease progression. In conclusion, our data indicate that infusion of T cells carrying a CD30.CAR containing a CD28 endodomain after lymphodepleting chemotherapy is safe, with limited toxicities at the dose levels tested. CD30.CAR expansion is improved with inclusion of pre-infusion standard lymphodepleting chemotherapy and appears to be associated with improved efficacy in relapsed patients (6/8 CR versus 1/6 CR, P = 0.03). Disclosures Rooney: Marker: Equity Ownership. Heslop:Marker: Equity Ownership; Cytosen: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Cell Medica: Research Funding; Gilead Biosciences: Membership on an entity's Board of Directors or advisory committees; Viracyte: Equity Ownership. Brenner:Marker: Equity Ownership.

Abstract Background: Adult T-Cell Lymphoma/Leukemia (ATLL) is a rare and aggressive HTLV-1 related peripheral T-cell lymphoma that occurs predominantly in Japan and the Caribbean basin. Acute (A) and lymphomatous (L) subtypes are the most aggressive forms with a median overall survival (OS) of 6-12 months despite chemotherapy. Typical immunophenotype (IP) of ATLL is CD4+/CD8- with strong co-expression of CD25. Atypical IP has been reported in ~10-20% of cases, and has been linked to a more aggressive disease in rare Japanese case reports. However, little literature exists on the Caribbean population. Kings County Hospital (KCH) and University Hospital of Brooklyn (UHB) serve a big Caribbean community in Brooklyn, New York. Our primary objective is to describe the clinicopathologic characteristics and treatment outcomes of our Caribbean patients. We also aim to evaluate the effect of IP on prognosis. Methods: We conducted a retrospective analysis of all patients diagnosed with HLTV1+ ATLL at KCH and UHB between 2005 and 2017. Diagnosis of ATLL was established based on clinical history, pathological findings and HTLV1 serum positivity. We included patients with A and L subtypes only. IP was based on flow cytometry from peripheral blood and/or immunostaining from lymph node biopsy. For the univariate analysis, outcomes were calculated using the log-rank test, and survival curves were estimated by Kaplan-Meier method. Results: We identified 63 patients with A and L subtypes. The median age was 54 with female predominance (65%). A and L subtypes were noted in 55% and 45% of patients respectively, and 95% had Ann Arbor stage III/IV. Two patients transformed to A subtype from chronic disease, and one patient transformed to L subtype from smoldering disease. Organ involvement at presentation was as follows: lymphadenopathy (80%), bone marrow (63%), hepatomegaly (25%), skin lesions (24%), bone lesions (23%), splenomegaly (21%), pleural effusions (14%), lung (11%), and CNS (8%). Hypercalcemia was noted in 47%, and only 4 patients had normal LDH. Out of 26 patients with a reported karyotype, 8 patients had abnormal cytogenetics (31%). Most patients received upfront EPOCH (78%) or CHOP chemotherapy (14%). The objective response rate (ORR) was 47% (complete response [CR] 16%, partial response [PR] 31%) and stable disease (SD) was achieved in 14%. None of the patients received antiviral therapy or consolidative stem cell transplant. The median duration of response was 2.1 months. The median OS was 5.8 months and median progression-free survival (PFS) was 4 months. Strikingly, 4 patients survived beyond 3 years including two who remain alive at 5+ years without further therapy. Of patients with relapsed/refractory (R/R) disease (85%), 35 patients (66%) received 2nd line treatment (mostly ICE chemotherapy: 27%). ORR was 21% (1 CR and 6 PR) and another patient had SD. For R/R patients, the median OS was 2.2 months and median PFS was 2 months. Univariate analysis showed that the following factors were associated with shorter OS and PFS: LDH > twice the upper limit of normal (p=0.002 and <0.001, respectively), bone marrow involvement (p<0.001), hypercalcemia >13 mg/dl (p<0.001), and absence of response to first line chemotherapy (p<0.001). Abnormal cytogenetics correlated with shorter PFS (p=0.04) but not OS (p=0.13). 14 patients had atypical IP (32%) with the following distribution: CD4- (3 patients), CD4+/CD8+ (3 patients), CD4-/CD8- (2 patients), CD25 dim (5 patients) and CD25- (1 patient). Among those who received chemotherapy, atypical IP was associated with shorter OS (p=0.04) and PFS (p=0.04) (Figure 1). Normal LDH correlated with OS beyond 1 year. Conclusion: Our large cohort of Caribbean patients with acute and lymphomatous subtypes of ATLL suggests a chemo-refractory and more aggressive disease compared with Japanese population, highlighting the need for novel therapies. In our patient population, incidence of atypical immunophenotype was higher than previously reported and was associated with worse PFS and OS. Disclosures: No relevant conflicts of interests to declare. Disclosures No relevant conflicts of interest to declare.

Waldenström’s macroglobulinemia (WM) is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics of WM in Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n=71) patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37–92 years) and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR) compared to conventional chemotherapy alone (92.9% versus 52.6%,P=0.006). The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73–111.07). Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients with WM.

Abstract Background: Autologous stem cell transplantation (ASCT) in conjunction with novel therapeutic drugs can dramatically improve response rates and the prognosis of patients with multiple myeloma (MM). However, most patients with MM are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper responses are required. Next-generation sequencing (NGS) and multiparameter flow cytometry (MFC) methods have been used to assess MRD. However, the lack of standardization of conventional MFC approaches has had a negative impact on its reproducibility. Recently, a next-generation MFC method (EuroFlow, NGF) has been developed by the EuroFlow Consortium and the International Myeloma Foundation (IMF) for a highly sensitive and standardized detection of MRD in MM. Aims: To compare the prognostic value of MRD detection in autografts in MM between NGS (Adaptive) and 8-color MFC method (EuroFlow, NGF), and also MRD levels between fresh and cryopreserved autografts. Methods: A total of 39 newly-diagnosed MM patients who underwent ASCT were enrolled in this study. Median age 60 at ASCT (range 41-69); males 22, females 17; ISS 1 (n=10), 2 (n=19), 3 (n=10). 10 patients showed high-risk chromosomal abnormalities (t(4;14) (n=9), del17p & t(4;14) (n=1)). The induction regimen was bortezomib-based chemotherapy. All patients received melphalan 200 mg/sqm as conditioning regimen before ASCT. 34 of 39 (87%) patients received maintenance therapy until progressive disease. The best response post-ASCT was as follows: 23sCR, 2CR, 12VGPR, 2PR. 39 autografts, one from each MM patient, were analyzed using NGF and NGS methods. The NGF method was based on a standardized lyse-wash-and-stain sample preparation protocol, the measurement of high numbers of cells and an optimized 8-color, 2-tubes, antibody panel, for accurate identification of plasma cells (PCs) and discrimination between phenotypically aberrant (aPC) and normal PC (nPC) (J Flores-Montero et al., Leukemia 2017). NGS-based MRD assessment was performed using Adaptive's standardized NGS-MRD Assay (Seattle, WA) (Martinez-Lopez et al., Blood 2014). To assess the correlation of MRD levels between fresh and cryopreserved autografts using NGF, 6 additional MM patients' autografts were used. Results: MRD levels in all 39 autografts were assessed using EuroFlow, while those in 32 of 39 (82%) were assessed with NGS due to limited availability of material for calibration. We identified abnormal plasma cells (aPC) in autografts based on multivariate analysis of individual cells from each patient (e.g. CD56+, CD19-, CyIgκ+, CD117+). Since there was a good correlation in MRD levels between fresh and thawed frozen autografts detected by EuroFlow (R=0.943, P=0.02), we assessed the MRD levels in thawed frozen autografts. For the MM MRD in autografts, the events from tube 1 and tube 2 were combined and a median of 7.3×106 (range: 2.2×106-37.6×106) events was acquired. The sensitivity of EuroFlow was 1×10-5-2×10-6 while that of NGS was 10-7 due to the high number of DNA derived from autografts (Takamatsu et al., Ann Oncol 2017). 21 of 39 (54%) cases were MRD positive by 8-color MFC while 22 of 32 (69%) cases were MRD positive by NGS. The correlation of MRD levels between 8-color MFC and NGS was relatively high (Fig. 1A). MRD negative by NGF (MRDMFC (-)) cases tended to show better PFS than MRDMFC (+) cases (P=0.145) (Fig. 1B) while MRD negative by NGS (MRDNGS (-)) cases showed significantly better PFS than MRDNGS (+) cases (P=0.03) (Fig. 1C). Furthermore, MRDMFC (-) MRDNGS (-) cases showed significantly better PFS than MRDMFC (-) MRDNGS (+) cases (P=0.01), but the PFS of MRDMFC (-) MRDNGS (+) cases was not different from that of MRDMFC (+) MRDNGS (+) cases (P=0.70). MRDMFC (-) and MRDNGS (-) cases showed better OS than MRDMFC (+) (P=0.14) and MRDNGS (+) (P=0.08) cases, respectively. Conclusions: Although EuroFlow is a fast and accurate method for detecting MRD of MM in autografts, in this study the NGS platform had a higher sensitivity and prognostic value than EuroFlow. The homogenous nature of the mobilized autograft relative to the focal nature of myeloma in bone marrow might provide a better sample to assess MRD. Figure 1. Figure 1. Disclosures Takamatsu: Celgene: Honoraria, Research Funding; Ono: Research Funding; Bristol-Myers Squibb: Research Funding; Janssen: Honoraria. Nakao:Novartis: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria.

Abstract Introduction Salvage high dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is used in fit patients with relapsed multiple myeloma (RMM) in clinical practice. However, the role of this approach in the era of continuous novel agent based treatment has not been defined in randomized trials. The ReLApsE trial compared lenalidomide/dexamethasone (Rd) re-induction, salvage HDCT/ASCT and lenalidomide (R) maintenance with standard continuous Rd in a randomized controlled multicenter trial. Methods Between 2010 and 2016, 282 patients were randomized of whom 277 constituted the intention-to-treat (ITT) population (arm B/A n=139/138). Arm B received 3 cycles of Rd (lenalidomide 25 mg, day 1-21; dexamethasone 40 mg, day 1, 8, 15, 22; 4 week cycles) re-induction, HDCT (melphalan 200 mg/m2), ASCT and R maintenance (10 mg daily) until progression (PD). Arm A was treated with Rd until PD. In both arms stem cells were harvested after the 3rd Rd cycle if no back-up transplant was available. Key inclusion criteria were 1-3 prior therapy lines, age ≤ 75 years, time to PD ≥ 12 months in case of front-line HDCT/ASCT and WHO PS ≤ 2. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall survival (OS), response rates and toxicity. ISRCTN16345835, Eudra CT-No: 2009-013856-61. Results Arm B and A were balanced regarding age (median 61.3 vs. 62.2 years), ISS (I/II/III in 62.6/24.4/13% vs. 59.7/31/9.3%) and WHO PS (0/1/2 in 69.1/30.9/0% vs. 76.1/23.2/0.7%). Almost all patients had only 1 prior therapy line (arm B: 94.2% vs. arm A: 93.5%) and had received front-line HDCT/ASCT (92.8% vs. 94.2%). More patients in arm B had high risk cytogenetic aberrations (HR-CA; 42.9% vs. 31.6%) based on a higher frequency of t(4;14) (20.2% vs. 10.1%). The overall response rate (≥ partial response; ORR) for arm B and A was 77.9% and 74.6% (p=0.57) with 49.3% and 47.1% (p=0.81) achieving ≥ very good partial response as best response. Within a median follow up of 36.3 months, 183 PFS events and 76 deaths occurred. Median PFS in the ITT population was 20.7 months in arm B and 18.8 months in arm A without a statistically significant difference (HR 0.87; 95% CI 0.65-1.16; p=0.34). Median OS was not reached (NR) in arm B vs. 62.7 months in arm A (HR 0.81; 95% CI 0.52-1.28; p=0.37). In arm B, 41 patients (29.5%) did not receive the planned HDCT/ASCT. Thus, exploratory landmark (LM) analyses from HDCT and the contemporaneous Rd cycle 5 in arm A were performed (median interval from randomization to HDCT/Rd cycle 5: 117/122 days; n=103[B]/114[A]). They showed a trend towards superior PFS (23.3 vs. 20.1 months; HR 0.74; p=0.09) and significantly superior OS (NR vs. 57 months; HR 0.56; p=0.046) in arm B vs. A. Multivariate analyses revealed significant associations of treatment in arm B with superior LM PFS (HR 0.6; p=0.01) and LM OS (HR 0.39; p=0.006). Other factors in the LM multivariate models showing significant associations with survival were HR-CA (PFS, OS), number of prior therapy lines (PFS), and age (PFS). The ORR in arm B after HDCT/ASCT was significantly higher than in arm A after Rd cycle 5 (82.3% vs. 69.6%; p=0.04). Grade ≥3 adverse events were reported in 83% (arm B) and 74.5% (arm A; p=0.11). Grade ≥3 leukopenia/neutropenia was reported in 61.5 vs. 24.8% (p<0.001), grade ≥3 thrombopenia in 45.2 vs. 11% (p<0.001) and grade ≥3 mucositis in 10.4% vs. 2.1% (p=0.005). No significant difference in grade ≥3 infections/infestations (33.3 vs. 27.6%; p=0.3) was observed. Eleven patients died on protocol treatment (B: 4 vs. A: 7). No deaths occurred in the HDCT/ASCT phase. Conclusions This is the first RCT comparing salvage HDCT/ASCT with continuous novel agent based treatment. No significant PFS or OS difference was observed in the overall trial population. However, HR-CA were more frequent in the HDCT/ASCT arm and ~30% of patients did not receive the planned HDCT/ASCT. Landmark analyses from the time of HDCT indicate superior PFS and OS in patients actually undergoing salvage HDCT/ASCT. Salvage HDCT/ASCT was safe with an expected increase in hematological as wells as gastrointestinal toxicity but without treatment-related mortality in patients up to the age of 75 years in this multicenter trial. However, the number of patients not undergoing salvage HDCT/ASCT and the approval of more active Rd-based triplet regimens after the initiation of this trial prevents definite conclusions on the role of salvage HDCT/ASCT. Disclosures Goldschmidt: Amgen: Consultancy, Research Funding; Novartis: Honoraria, Research Funding; ArtTempi: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Mundipharma: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Adaptive Biotechnology: Consultancy; Chugai: Honoraria, Research Funding. Baertsch:Takeda: Consultancy; Novartis: Consultancy, Research Funding. Raab:Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Hillengass:Novartis: Honoraria, Other: Advisory Board; Sanofi: Research Funding; Takeda: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; amgen: Consultancy, Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Celgene: Consultancy, Honoraria, Other: Advisory Board, Research Funding. Graeven:AbbVie: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees. Fenk:Takeda: Honoraria; Bristol-Meyers Squibb: Honoraria, Other: travel grant; Celgene: Honoraria, Other: Travel grant, Research Funding; Janssen: Honoraria; Amgen: Honoraria. Haenel:Novartis: Honoraria; Roche: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Scheid:Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; BMS: Honoraria; Amgen: Honoraria. Salwender:Celgene: Honoraria, Other: travel suppport, Research Funding; Janssen: Honoraria, Other: travel support, Research Funding; Novartis: Honoraria, Other: travel suppport, Research Funding; Takeda: Honoraria; Amgen: Honoraria, Other: travel suppport, Research Funding; Bristol-Myers Squibb: Honoraria, Other: travel suppport, Research Funding. Weisel:Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Colorectal cancer (CRC) is a leading cause of morbidity and mortality affecting more than 1.4 million people annually worldwide. Due to the aggressive and asymptomatic nature approximately 60% of CRC sufferers are diagnosed at or beyond stage III resulting in prognostic outlook relying heavily on the successful application of chemotherapeutic treatment. Chemotherapeutic agents oxaliplatin, 5-fluorouracil and irinotecan represent the backbone of CRC treatment, significantly enhancing tumour regression and patient survival. However successful application of these cytotoxic chemotherapies is hindered by undesirable neurological and gastrointestinal (GI) side-effects. Chronic GI side-effects often result in dose limitations and, in severe circumstances, cessation of anti-cancer treatment, presenting a constant challenge in efficient and tolerable treatment of CRC. It is believed that chemotherapy-induced GI side-effects are a direct result of intestinal mucositis; however adjacent systems such as the enteric nervous system have been overlooked. This thesis aims to uncover the effects of in vivo administration of anti-cancer chemotherapeutics oxaliplatin, 5-fluorouracil and irinotecan on the enteric nervous system and GI function, and examine the neuroprotective efficacy of a cytoprotective agent BGP-15.

This study examined the relationship between health status, social support, psychological symptoms and coping skills in patients receiving chemotherapy and/or radiotherapy in Thailand. The convenience sample consisted of 249 patients receiving chemotherapy in the initial test and 158 receiving chemotherapy in the second test. Also, a total of 209 patients receiving radiotherapy participated in the study.

Chemotherapy is an effective first-line treatment against cancer; however, it induces a myriad of serious sequalae, including skeletal muscle dysfunction and wasting (SMDW) and fatigue, which we hypothesise is underpinned by mitochondrial dysfunction. When chemotherapy-induced (CI) SMDW is instigated in childhood, it often endures and manifests over the lifespan resulting in exacerbated morbidity and, in some cases, mortality. Despite much research having investigated individual chemotherapeutic agents and their effect on the skeletal muscle in mice (including our own), these models failed to evaluate the potential interactions between agents in a poly-pharmaceutical regimen, or, the effects of long-term and multi-staged chemotherapy regimens like that used in hospitals world-wide. Therefore, this thesis investigated the impact that gold-standard chemotherapy regimens used to combat the three common childhood cancers: acute lymphoblastic leukaemia (ALL), non- Hodgkin’s Burkitt lymphoma (NHBL) and medulloblastoma, on the skeletal muscle system in healthy juvenile mice and monitored the effects of treatment endured over the lifespan. After establishing pre-clinical animal models for three gold-standard chemotherapy regimens, we showed that, regardless of regimen, eight weeks of treatment to four-week-old mice induced considerable skeletal muscle dysfunction which was characterised by significant muscle weakness, fatigability and, in 2 of the 3 regimens, lean mass loss. Although the age of onset of these sequalae were variable (varying between eight-weeks and 30-weeks of life), mitochondrial dysfunction was evident, identifying a point for therapeutic intervention. As such, we investigated the efficacy of daily Idebenone treatment (a powerful antioxidant and mitochondrial Co-Q10 analogue) against mitochondrial dysfunction and thus CI-SMDW. Idebenone co-therapy greatly improved mitochondrial performance in chemotherapy- treated mice, as well as protecting against lean mass loss and improving overall strength in the more aggressive chemotherapy regimen used against NHBL. Moreover, Idebenone co- therapy was shown to completely abate chemotherapy-induced mortality in the NHBL regimen, reducing mortality from 77% to zero. This thesis shows that childhood chemotherapy, regardless of the aggressiveness of the regimen or the classes of drugs used, induces life-long SMDW which is likely contributed to by mitochondrial dysfunction. The mitochondrial targeting therapeutic, Idebenone, shows promising potential for clinical application against the SMDW sequalae and mortality induced by some regimens, with the potential to improve childhood chemotherapy patient outcomes and survivability.

Cisplatin, carboplatin and oxaliplatin are platinum-based agents that are amongst the most widely used drugs for the treatment of cancer in the clinical setting. Despite their therapeutic efficacy, these platinum-based drugs are associated with a myriad of dose-limiting side-effects. These include acute and chronic peripheral neuropathies (paraesthesias, dysaesthesias), and gastrointestinal complications (nausea, vomiting, constipation and diarrhoea). These side-effects decrease quality of life and cause life-threatening cardiac and renal sequeale consequent to malnutrition, dehydration and fluid and electrolyte imbalances, which in severe cases, can lead to death. Extensive research into the mechanisms underlying chronic peripheral neuropathies associated with platinum-based agents has focused on drug accumulation within the dorsal root ganglia (DRG). Only recently, a few studies have demonstrated damage to the enteric nervous system (ENS) following platinum-based chemotherapy. The ENS is an intrinsic and complex orchestration of nerves embedded throughout the entirety of the gastrointestinal tract innervating the musculature and mucosa. The mechanisms underlying ENS toxicity remain unknown. Furthermore, the gastrointestinal tract receives extrinsic innervations and it is also unknown if these nerves are vulnerable to platinum-based drugs. Platinum-based drugs mediate their cytotoxic effects through the formation of interstrand and intrastrand DNA adducts, particularly binding to the N7 position of guanine nucleotides. Essentially, these platinum lesions inhibit DNA replication through the distortion of the helical structure. DNA damage typically results in the induction of canonical apoptotic cascades. Until recent years apoptosis was deemed an immunologically ‘silent’ or ‘tolerogenic’ event. However, unlike cisplatin and carboplatin, there is substantial evidence shown in models of cancer that oxaliplatin prompts a fatal immune response against cells committed to apoptosis. This phenomenon is termed ‘immunogenic cell death’. Oxaliplatin-induced cytotoxicity results in the hallmark presentation of damage-associated molecular patterns (DAMPs) which can be recognised by antigen-presenting cells, and thus, stimulating phagocytosis of apoptotic cells and/or debris. The gastrointestinal tract harbours ~70% of the body’s immune system, and so it is unknown whether oxaliplatin treatment can induce changes in immunological responses which may directly or inadvertently induce ENS damage. Given the bi-directional communication between the immune and nervous systems, exploring the consequences of oxaliplatin-induced cytotoxicity and potential immunogenicity may provide insight into the multifaceted mechanisms underlying neuronal damage and death which impact gastrointestinal function.