Comparing the adverse effects of platinum in combination with etoposide or irinotecan in previously untreated small‐cell lung cancer patients with extensive disease: A network meta‐analyses

BACKGROUND: The safety of front‐line chemotherapies for the treatment of extensive stage small‐cell lung cancer (ED‐SCLC) is uncertain. We carried out a network meta‐analysis to compare the toxicity of different therapies for ED‐SCLC. METHODS: We searched EMBASE, PubMed, CENTRAL and clinicaltrials.gov. We performed network meta‐analysis on hematological (anemia, leukopenia, neutropenia, and thrombocytopenia) and non‐hematological toxicities (diarrhea, infection, and nausea and vomiting). RESULTS: Nine studies with 2317 patients were included. Etoposide with carboplatin (EC) was associated with a higher incidence of anemia (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.13–3.63), leukopenia (OR 2.67, 95% CI 1.25–5.72), neutropenia (OR 12.08, 95% CI 2.13–68.66), and thrombocytopenia (OR 2.73, 95% CI 1.27–5.85) compared with irinotecan with carboplatin (IC). Similarly, etoposide with cisplatin (EP) was associated with a higher incidence of anemia (OR 1.70, 95% CI 1.13–2.56), leukopenia (OR 2.65, 95% CI 1.34–5.28), neutropenia (OR 5.70, 95% CI 2.93–11.10), and thrombocytopenia (OR 3.26, 95% CI 1.66–6.38) compared with irinotecan with cisplatin (IP). EC was associated with a lower incidence of diarrhea (OR 0.26, 95% CI 0.10–0.68) compared with IC, and EP was associated with a lower incidence of diarrhea (OR 0.09, 95% CI 0.03–0.25) and nausea and vomiting (OR 0.53, 95% CI 0.33–0.84) than IP. CONCLUSIONS: Hematological toxicities were most common in EC‐treated patients, while the lowest incidence occurred with IP treatment. The IP regimen was associated with the highest incidence of toxicities of the digestive tract, while the lowest incidence occurred with EC treatment.