The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review

Abstract

BackgroundAlthough acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle.MethodsA systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy.ResultsFourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1–4) was the most common event with prevalence ranging from 4–98%, followed by haematological (1.4–81%) and gastrointestinal (1.2–67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m2) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase.ConclusionDespite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.

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

“…In contrast to the previous reports [4,16], haematological toxicity was the main adverse advent recorded for dose reduction, followed by neuropathy plus haematological toxicity and neuropathy alone, respectively, across cycles ( Figure 5). Neuropathy along with any other adverse events resulted in dose reduction in 37-51% of the patients in any given cycle.…”

“…Additionally, patients who received FOLFOX treatment had longer survival times, followed by XELOX and oxaliplatin monotherapy (11.5 vs 9 vs 4.5 months, respectively). Survival analysis (by factor) confirmed that patients who completed 8 cycles of chemotherapy and those who received >850 mg/m 2 cumulative dose of oxaliplatin had longer survival times, indicating that delay or cessation leads to poorer treatment outcome as reported in this and prior studies [12,16]. Moreover, the IDEA clinical trial study failed to confirm overall noninferiority of 3 vs. 6 months treatment of XELOX and FOLFOX regimens but did show inferiority of shorter duration FOLFOX treatment in high risk subgroups [25][26][27].…”

“…Moreover, it is not explained in the literature why, and to what extent [4], the doses of other combined anti-cancer drugs need to be reduced when the patients develop neuropathy. e absence of detailed reporting of the specific types of adverse effects of each drug produced and the measures taken for single or combined drugs make patient management and treatment outcome poor as shown in our previous study [16]. Furthermore, in the current study, haematological toxicity was the main criteria for dose reduction, followed by neuropathy and gastrointestinal adverse effects [19].…”

Cancer treatment and survivorship statistics, 2019

“…Neuropathy is a common side effect of chemotherapy regimens typically used for colorectal cancer that contain oxaliplatin . Periodic or chronic diarrhea occurs in approximately one‐half of colorectal cancer survivors .…”

Platinum‐induced peripheral neurotoxicity: From pathogenesis to treatment

“…The large majority (89%) of a cohort of 346 patients under fluorouracil, leucovorin, and oxaliplatin (FOLFOX) reported at least one symptom of acute oxaliplatin neurotoxicity within the first cycle, namely sensitivity to cold (71%), throat discomfort (63%), or muscle cramps (42%), with a peak at day 3, later improvement, and incomplete remission between treatments . According to a systematic review, acute oxaliplatin neuropathy (Common Terminology Criteria Adverse Events, CTCAE grades 1‐4) occurred in 4% to 98% of patients, with moderate to severe toxicities commonly encountered in patients receiving a large dose of oxaliplatin (> 85 mg/m 2 ) and/ or combined drugs …”