Impact of peripheral neuropathy induced by platinum in first-line chemotherapy on second-line chemotherapy containing paclitaxel for advanced gastric cancer.

Abstract

132 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of platinum and paclitaxel (PTX) persisting for long time. In the Gastric Cancer Treatment Guideline (Japanese Gastric Cancer Association, 2018), first-line chemotherapy with fluoropyrimidine plus platinum followed by taxane based chemotherapy is recommended. It is not well known how much CIPN by platinum in the first-line chemotherapy affect the tolerability of second-line chemotherapy containing PTX (second-PTX). Methods: The subjects were advanced gastric cancer patients who received second-PTX after the platinum-containing first-line chemotherapy between March 2015 and June 2018. Patients were divided into two groups according to prior platinum: oxaliplatin (prior L-OHP) and cisplatin (prior CDDP) groups. CIPN was graded according to CTCAE ver.4. Severity of CIPN, dose reduction and discontinuation due to CIPN during the second-PTX were compared between the two groups. Results: 109 patients (50 prior L-OHP group and 59 prior CDDP group) were included in this retrospective study. The severity of CIPN just before second-PTX was 46% for grade 1 and 12% for grade 2 in the prior L-OHP group, and 8.5% and 0% in the prior CDDP group. The initial dose of PTX was reduced in 59 % of the prior L-OHP and in 39 % of the prior CDDP group. The worst grade of CIPN during second-PTX was 40% for grade 1, 34% for grade 2, 14% for grade 3 in the prior L-OHP group, and 33.9%, 20.3%, 0% in the prior CDDP group. Median time to grade 2 neuropathy during second-PTX was 2.5 months in the prior L-OHP group and 8.6 months in the prior CDDP group (p = 0.0004). CIPN-related dose reduction of PTX were 12.0% in the prior L-OHP group and 3.4% in the prior CDDP group (p = 0.177). Discontinuation of second-PTX due to CIPN were 10.0% in the prior L-OHP group and 5.1% in the prior CDDP group (p = 0.541). Conclusions: The severity of CIPN and tolerability of the second-PTX may be affected by prior platinum, L-OHP or CDDP, in the first-line chemotherapy for advanced gastric cancer.