The risk factors for oxaliplatin-induced peripheral sensory neuropathy and thrombocytopenia in advanced gastric cancer

Cancer Chemother Pharmacol. 2018 Oct;82(4):625-633. doi: 10.1007/s00280-018-3652-2. Epub 2018 Jul 24.

Abstract

Purpose: Peripheral sensory neuropathy (PSN) and thrombocytopenia are the main dose-limiting toxicities of oxaliplatin for the treatment of advanced gastric cancer (AGC). Because the risk factors for those toxicities in practice have not been clarified, we conducted this prospective study.

Methods: AGC patients who received oxaliplatin-based therapy at any of seven institutions participating in the Kyushu Medical Oncology Group were assessed after we obtained written informed consent.

Results: A total of 60 patients including 39 males and 21 females were examined. The median age was 66 years. The numbers of patients receiving oxaliplatin as the first, second, or third and later lines of therapy were 39, 16, and 5, respectively. An initial dose of 130, 100, or < 100 mg/m2 oxaliplatin was administered to 12, 39, and 9 patients, respectively. S-1 or capecitabine as a concomitant drug was administered in 54 and 6 patients, respectively. In multivariate analysis, the comorbidity of diabetes mellitus was associated with ≥ grade 2 thrombocytopenia (p = 0.035). No significant risk factor was associated with ≥ grade 2 PSN. However, the accumulated dose of oxaliplatin exhibited a strong correlation with ≥ grade 2 PSN (p = 0.0043), and the predicted accumulated dose of oxaliplatin in which 10% of patients developed ≥ grade 2 PSN was 800 mg/m2. The frequency of PSN in subsequent paclitaxel therapy in patients with ≥ grade 2 or worse PSN in oxaliplatin-based chemotherapy did not increase compared to those with none or grade 1 PSN in oxaliplatin.

Conclusion: Thrombocytopenia in AGC patients with diabetes mellitus should be carefully monitored during oxaliplatin-based therapy.

Keywords: Cisplatin; Gastric cancer; Oxaliplatin; Paclitaxel.

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Blood Cell Count / methods
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypesthesia* / chemically induced
  • Hypesthesia* / diagnosis
  • Japan
  • Male
  • Neoplasm Staging
  • Oxaliplatin* / administration & dosage
  • Oxaliplatin* / adverse effects
  • Peripheral Nervous System Diseases* / chemically induced
  • Peripheral Nervous System Diseases* / diagnosis
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / pathology
  • Thrombocytopenia* / chemically induced
  • Thrombocytopenia* / diagnosis

Substances

  • Antineoplastic Agents
  • Oxaliplatin