Variability of Oxaliplatin-Induced Neuropathic Pain Symptoms in Each Cycle and Its Implications on the Management of Colorectal Cancer Patients: A Retrospective Study in South Western Sydney Local Health District Hospitals, Sydney, Australia

Abstract

Oxaliplatin-induced neuropathic pain limits treatment compliance. However, the variability of neuropathic pain symptoms in each cycle for individual patients and the impacts on treatment compliance remain untested. Data from 322 adult patients who received oxaliplatin-based chemotherapy were extracted based on pattern of chemotherapy, adverse events, and patient survival. Cox regression and survival analyses were employed. Seventy-eight percent of patients developed neuropathic pain that oscillated between a complete absence and presence on a cycle-by-cycle basis. Consequently, the presence of neuropathy in one cycle did not predict the incidence of neuropathy in subsequent cycles. This implies that neuropathic pain need not be a sufficient criterion to reduce, delay, or cease chemotherapy. In the case of multiple system adverse events during combined drug treatment, the responsible cause for dose reduction was not identified. Cox regression analysis revealed that middle age (61–78 years old,P=0.003) and oxaliplatin cumulative dose <850 mg/m2(P=0.002) were associated with patient mortality. Completion of chemotherapy (8 cycles) and cumulative dose >850 mg/m2of oxaliplatin prolonged the median survival time by 8 and 5 months, respectively. As oxaliplatin-induced neuropathic pain fluctuates across cycles in a manner that varies from patient-to-patient, current assumptions on the predictive nature of the emergence of neuropathy (and its impact on treatment compliance) need to be reconsidered. Detailed patient-by-patient analysis of adverse events should be applied to future studies in order to determine the efficacy of current treatments (and future interventions) and whether neuropathic pain should be retained as a criterion to vary the treatment. Additionally, when two or more system toxicities occurred in cases of combined drug treatment, the causes for drug reduction should be separately recorded.

Patient‐reported motor chemotherapy‐induced peripheral neuropathy impacts function in advanced colorectal cancer survivors receiving chemotherapy: A cross‐sectional study

“…The prevalence of neuropathic pain (20%) in this study is similar to the French CRC survivors 5 years after FOLFOX chemotherapy of 15.4% (Selvy et al, 2020), but higher than a study that reported 9% in long‐term CRC survivors (Bonhof et al, 2020) and lower than Australian individuals with cancer receiving oxaliplatin‐based chemotherapy at 78% (Gebremedhn et al, 2019). The difference may be due to Bonhof et al (2020) using the European Organization of Research and Treatment Cancer Quality of Life Questionnaire‐CIPN 20‐item scale (EORTC QLQ‐CIPN 20) for neuropathic pain measures which are not as specific for neuropathic pain as IDQ utilized in our study.…”

“…The difference may be due to Bonhof et al (2020) using the European Organization of Research and Treatment Cancer Quality of Life Questionnaire‐CIPN 20‐item scale (EORTC QLQ‐CIPN 20) for neuropathic pain measures which are not as specific for neuropathic pain as IDQ utilized in our study. The Australian study asked only about the frequency and magnitude of acute and chronic neuropathies in cancer survivors who received oxaliplatin‐based chemotherapy (Gebremedhn et al, 2019), while our study did not specify acute from chronic neuropathic pain and focused solely on advanced CRC individuals. The prevalence rate of neuropathic pain in the literature was highly inconsistent.…”

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

“…Quantitative sensory testing (QST) examines subjective sensory function by measuring the abnormal detection and pain thresholds to several sensory modalities. The usefulness of these non-invasive psychophysical measurements in the clinic setting for detecting subclinical neurologic changes early on to identify patients that will experience OXAIPN has been largely explored [ 12 , 20 , 20 , 42 , 51 , 53 , 54 , 56 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ].…”

Mapeamento de fatores clínicos preditivos da neuropatia sensorial periférica induzida por oxaliplatina: revisão sistemática

“…A referência à dose cumulativa (m²) é a mais expressiva quantitativamente e emerge em treze estudos dessa revisão 22,24,25,27,29,31,33,[35][36][37][42][43][44] . Outros dois referem-se ao início das manifestações de Neuropatia, a partir de ciclos específicos, em associação com determinado somatório, média ou mediana de dose cumulativa 22,25 . Apenas Hsu, et al 24 estudo a menciona como fator preditivo, sem, contudo, delimitar valor numérico.…”