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

Int J Clin Oncol. 2020 Apr;25(4):595-601. doi: 10.1007/s10147-019-01598-5. Epub 2019 Dec 18.

Abstract

Background: Fluoropyrimidine plus platinum, followed by paclitaxel (PTX) plus ramucirumab is a recommended treatment strategy for advanced gastric cancer (AGC). We investigated how peripheral neuropathy (PN), induced by platinum in first-line chemotherapy, affected the tolerability of second-line chemotherapy with PTX (2nd-PTX).

Methods: The subjects were AGC patients who received second-line chemotherapy with PTX (2nd-PTX) after the failure of platinum-based chemotherapy between March 2015 and June 2018. We retrospectively reviewed PN severity, and dose reduction and/or discontinuation due to PN during 2nd-PTX, and compared the cumulative incidence of grade 2 PN between the two groups according to first-line chemotherapy containing oxaliplatin (L-OHP) or cisplatin (CDDP).

Results: The L-OHP and CDDP groups consisted of 50 patients each. PN severity before 2nd-PTX was grade 1/2 in 46/12% of patients in the L-OHP group, and 100/0% in the CDDP group. The worst grades of chemotherapy-induced PN during 2nd-PTX were grades 1/2/3 in 40/34/14% of patients in the L-OHP group, and 36/18/0% in the CDDP group. Median time to grade 2 PN after starting second-PTX was 2.5 months in the L-OHP group and 8.6 months in the CDDP group (hazard ratio 3.34, p = 0.002). The frequencies of a PN-related dose reduction and/or discontinuation of PTX were 18% in the L-OHP group and 8% in the CDDP group (p = 0.234).

Conclusions: The severity of PN and tolerability of 2nd-PTX may be affected by first-line chemotherapy with L-OHP or CDDP for AGC.

Keywords: Cisplatin; Gastric cancer; Oxaliplatin; Paclitaxel; Peripheral neuropathy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cisplatin / administration & dosage
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxaliplatin / administration & dosage
  • Paclitaxel / administration & dosage
  • Peripheral Nervous System Diseases / chemically induced*
  • Ramucirumab
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • Oxaliplatin
  • Paclitaxel
  • Cisplatin