Risk of second primary cancers in cancer patients treated with cisplatin: a systematic review and meta-analysis of randomized studies

BMC Cancer. 2017 Dec 19;17(1):871. doi: 10.1186/s12885-017-3902-4.


Background: Case reports, retrospective analyses, and observational studies have linked the use of cisplatin to increased risk of second cancers, especially life-threatening secondary leukemia. We therefore performed a systematic review and meta-analysis to evaluate the risk of second cancers associated with receipt of cisplatin-based chemotherapy in randomized controlled trials (RCTs).

Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant RCTs comparing cisplatin- versus non-cisplatin-containing chemotherapy with data on second cancers. We extracted data about study characteristics and second cancers, especially leukemia/ myelodysplasia. The primary and secondary outcomes were the odds ratios (ORs) for all second cancers and for secondary leukemia/ myelodysplasia, respectively.

Results: We identified 28 eligible trials with 7403 patients. Second cancers were reported in 143 patients, including 75 patients in the cisplatin arm and 68 in the non-cisplatin arm (raw event rates of 1.91 and 1.96%, respectively). The pooled OR for risk of all second cancers associated with cisplatin-based chemotherapy was 0.95 (95% confidence interval (CI): 0.67-1.33, P = 0.76). Secondary leukemia/ myelodysplasia was reported in 14 patients on cisplatin arms and in 6 patients on non-cisplatin arms of 11 eligible RCTs with 2629 patients (raw event rates of 1.09 and 0.45%, respectively; pooled OR = 2.34, 95%CI 0.97-5.65, P = 0.06).

Conclusion: Cisplatin was not associated with a significantly increased risk of second cancers compared with non-cisplatin-based chemotherapy. There is a non-significant trend to increased risk of leukemia/ myelodysplasia and the absolute risk was low. The concern about risk of second cancers should not influence decisions to use an efficacious regimen containing cisplatin.

Keywords: Cisplatin; Randomized controlled trials; Second cancer.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use
  • Female
  • Humans
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology*
  • Neoplasms / pathology
  • Neoplasms, Second Primary / chemically induced
  • Neoplasms, Second Primary / epidemiology*
  • Neoplasms, Second Primary / pathology
  • Retrospective Studies


  • Cisplatin