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.
Limited information is available about the effect of bleomycin administration on the development of pulmonary toxicity in metastatic germ cell tumors (GCT).



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.



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).



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.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it.
Andrea
A
Necchi
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Rosalba
R
Miceli
Hassan II University Hospital, Fez, Morocco.
Karima
K
Oualla
UAB Comprehensive Cancer Center, Birmingham, AL.
Guru
G
Sonpavde
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Patrizia
P
Giannatempo
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Daniele
D
Raggi
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Nicola
N
Nicolai
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Roberto
R
Boffi
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Alessandra
A
Busia
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Luigi
L
Mariani
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Roberto
R
Salvioni
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage* / Q000009:adverse effects; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D009362:Neoplasm Metastasis; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin
Bleomycin; Germ cell tumor; Meta-analysis; Pulmonary toxicity; Testicular cancer