Effect of Bleomycin Administration on the Development of Pulmonary Toxicity in Patients With Metastatic Germ Cell Tumors Receiving First-Line Chemotherapy: A Meta-Analysis of Randomized Studies

In a trial-level meta-analysis of randomized studies, bleomycin administration was independently significantly associated with the development of pulmonary toxicity in patients with metastatic germ cell tumors receiving first-line chemotherapy. This effect was mainly seen with respect to all-Grade pulmonary toxicity. This study provided a further argument in favor of reducing the burden of curative chemotherapy in these highly curable malignancies. Background: Limited information is available about the effect of bleomycin administration on the development of pulmonary toxicity in metastatic germ cell tumors (GCT). Patients and Methods: A literature search was conducted to identify randomized trials of first-line chemotherapy for GCT. We conducted univariate and multivariate analyses using random effects models to evaluate the predictive role of bleomycin administration in the development of all Grade and Grade 3 to 4 (G3-4) pulmonary toxicity. The results were adjusted for length of follow-up, prognostic risk group, year of treatment, presence of lung metastases, and primary mediastinal GCT. Results: Fifty-three study arms of 25 phase II and III trials encompassing 6498 patients were selected: 40 that used bleomycin (n = 5093) and 13 that did not (n = 1405). The pooled probability of all-Grade pulmonary toxicity in the bleomycin and nonbleomycin arms was 11.7% (95% confidence interval [CI], 8.4%-16.0%) and 1.7% (95% CI, 0.7%-4.2%), respectively. Univariate analysis indicated that bleomycin administration was associated with the incidence of all-Grade (odds ratio [OR], 7.57; 95% CI, 2.84-20.18; Wald test P < .001) and G3-4 pulmonary toxicity (OR, 5.19; 95% CI, 1.57-17.16; P = .007). Multivariate analysis showed a significant association of bleomycin administration with the incidence of all-Grade pulmonary toxicity (OR, 4.14; 95% CI, 1.36-12.59; P = .012) and a trend toward significance for G3-4 toxicity (OR, 2.24; 95% CI, 0.91-5.51; P = .080). Conclusion: We quantified the bleomycin-associated effect on the development of pulmonary toxicity in patients with GCT who received first-line chemotherapy. This information might be useful for planning clinical trials aimed at reducing chemotherapy as well as to inform patients in the clinic. (C) 2016 Elsevier Inc. All rights reserved.