Abstract 713P
Background
In 2014, the GETUG 13 trial has established the role of early intensified treatment for men with poor prognosis germ-cell tumors (GCT) and unfavorable tumor marker decline (Fizazi K, Lancet Oncol 2014). Patients with unfavorable marker decline were randomized after 1 cycle of BEP to receive either 3 additional BEP or dose-dense chemotherapy with personalized cumulative doses of bleomycin (potentially exceeding the 300 mg recommended threshold) based on serial lung function assessments. We assessed pulmonary toxicity of this strategy.
Methods
203 patients were randomized (105 in the dose-dense group, 98 in the BEP group). Pulmonary function tests were performed at baseline, before the 4th cycle in each arm and before the last and 5th cycle in the dose-dense arm. Bleomycin was not administered in case of clinical lung toxicity or if the respiratory function test showed a diffusing capacity of the lung for CO divided by the alveolar volume ratio (DLCO/VA) <65%. Clinical lung toxicity was assessed at each cycle and follow-up visit (median follow-up= 4.1 years). Pre-planned toxicity analyses were conducted on an intention-to-treat basis.
Results
The median cumulative bleomycin dose was 430 mg (range: 0-526 mg) and 360 mg (range: 0-360 mg) in the dose-dense arm and the BEP control arm, respectively (p<0.0001). Grade 3-4 lung toxicity was reported in 9 (8.6%) and 11 (11.2%) patients during chemotherapy, respectively (p=0.54). One patient in each arm still had grade 3-4 lung toxicity after chemotherapy, which improved with time with grade 1-2 toxicity at last follow-up. The DLCO/VA ratio decreased by 21.4% and 11.5% compared to baseline after 3 cycles of chemotherapy in the dose-dense and the BEP arm, respectively (p=0.0022). 25 (24%) and 6 (6%) patients discontinued bleomycin at cycle 4, respectively. In the dose-dense arm, 13 additional patients (12.4%) did not receive bleomycin at cycle 5.
Conclusions
This analysis confirms that the GETUG 13 dose-dense chemotherapy regimen can be safely used in men with poor-prognosis NSGCT with high personalized cumulative doses of bleomycin using strict lung function criteria, leading to no excess of short-term or long-term lung toxicity.
Clinical trial identification
NCT00104676; EU-20502.
Editorial acknowledgement
Legal entity responsible for the study
GETUG.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.