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

Abstract

Background: Although 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.

Methods: A 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.

Results: Fourteen 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.

Conclusion: Despite 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.

Keywords: Acute neuropathy; Chronic neuropathy; Colorectal cancer; Oxaliplatin.

Fig. 1

PRISMA flow diagram of included and excluded studies

Fig. 2

Individual plot of quality assessment for reviewed studies. Each study was initially assessed against 12 previously used criterial [39]. In the current study two additional criteria (criteria 13 and 14, as per Table 1) were included in order to assess the impact of acute neuropathy on treatment compliance in the first 14 days. The cumulative scores for successive criterion in each study are joined by a connecting line; based on the final cumulative score (criterion 14) studies were deemed to be of low (< 7), medium (7–9) and high quality (≥10). The addition two criteria revealed that only 2 of the 14 (highlighted in red) studies documented the impact of acute neuropathy in the first 14 days on treatment

Fig. 3

Reported incidences of acute neuropathy in the first cycle (≤14 days). Nine of 14 studies reported acute neuropathy symptoms in 4–98% of patients. In other studies, the incidence of neuropathy was not clearly identified. One other study, neuropathy was reported as grade 2–4 (percentage value was not reported) [37]