An integrated analysis of hyponatremia in cancer patients receiving platinum-based or nonplatinum-based chemotherapy in clinical trials (JCOG1405-A)

// Yasumasa Ezoe 1 , Junki Mizusawa 2 , Hiroshi Katayama 2 , Kozo Kataoka 2 and Manabu Muto 1 1 Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan 2 Japan Clinical Oncology Group (JCOG) Data Center/Operations Office, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan Correspondence to: Manabu Muto, email: mmuto@kuhp.kyoto-u.ac.jp Keywords: hyponatremia; platinum agent; cisplatin; carboplatin; risk factors Abbreviations: JCOG: Japan Clinical Oncology Group; SIADH: syndrome of inappropriate antidiuretic hormone secretion; NCI-CTC: National Cancer Institute-Common Toxicity Criteria; CI: confidence interval Received: October 27, 2017 Accepted: December 01, 2017 Published: December 20, 2017 ABSTRACT Background: Hyponatremia is a common electrolyte abnormality in cancer patients who receive chemotherapy. Among anticancer agents, platinum-based agents are reported to cause chemotherapy-induced hyponatremia. However, the actual incidence and risk factors remain unknown. Results: The reports of 29 trials were analyzed. The incidence of grade 3/4 hyponatremia was 11.9% in patients treated with platinum-based chemotherapy and 3.8% in those treated with nonplatinum-based regimens ( P < 0.01). Univariable analysis revealed a high incidence of hyponatremia in patients receiving cisplatin, three-drug combination regimen, two-drug combination regimen with amrubicin or irinotecan, or high-dose cisplatin (weekly equivalent cisplatin dose ≥20 mg/m 2 ), and in patients with small-cell lung cancer. Conclusion: This is the first report of the actual incidence and the potential risk factors of chemotherapy-induced hyponatremia. Careful monitoring of serum sodium level is needed when platinum-based chemotherapy is administered. Methods: This study included all clinical trials of systemic chemotherapies for solid cancers that were conducted by the Japan Clinical Oncology Group (JCOG) after January 2000 and of which the patient enrolment was completed by January 2014. The latest reports of each trial were used for analysis. The incidence of chemotherapy-induced grade 3/4 hyponatremia and the potential risk factors were investigated with univariable analysis.