Abstract
BackgroundCase 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).MethodsWe 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.ResultsWe 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).ConclusionCisplatin 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.
Highlights
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 performed an up-todate systematic review and meta-analysis to evaluate the effect of cisplatin on risk of second cancer in patients treated for their first cancer in Randomized controlled trials (RCT) with arms that compared chemotherapy regimens that did and did not include cisplatin
Of the 28 RCTs, 2 trials reported no incidence of any second cancers in both cisplatin and non-cisplatin arms, 15 trials reported the detailed information of cancer types of second cancers (10 trials reported incidence of secondary leukemia/myelodysplasia only), 11 trials did not provide detailed information of types of second cancers (Additional file 1: Table S1)
Summary
Retrospective analyses, and observational studies have linked the use of cisplatin to increased risk of second cancers, especially life-threatening secondary leukemia. We 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). Strong dose-response relationships between cumulative cisplatin dose and secondary leukemia risk (p < .001) were demonstrated in both studies [12, 13] These studies have seriously raised the concern about possible second cancer risk with the use of cisplatin. We performed an up-todate systematic review and meta-analysis to evaluate the effect of cisplatin on risk of second cancer in patients treated for their first cancer in RCTs with arms that compared chemotherapy regimens that did and did not include cisplatin
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