The effect of pulmonary function testing on bleomycin dosing in germ cell tumours

Background/Aim: The utility of pulmonary function testing (PFT) to detect bleomycin-induced pneumonitis is controversial. We describe its impact on bleomycin dosing in a phase 2 trial of accelerated BEP (bleomycin, etoposide, cisplatin) for advanced germ cell tumours. 

Methods: There were 12 planned weekly bleomycin doses for intermediate-risk and poor-risk disease and nine for good-risk disease. Clinical assessments, chest X-ray, diffusing capacity of lung for carbon monoxide (DLCO) and forced vital capacity (FVC) were performed bi-weekly. Bleomycin was ceased for predefined clinical/radiological evidence of pulmonary toxicity and a >25% reduction in DLCO or FVC. We determined doses planned, received and omitted and patients receiving all, ≥two-thirds, two-thirds of planned bleomycin doses.

Results: Of 43 eligible patients, 30% had lung metastases. Of 471, 375 (80%) of planned bleomycin doses were received, and 30% received <two-thirds of their planned doses, all for reductions in DLCO. No patient developed other evidence of pulmonary toxicity. Patients with lung metastases were 1.5 times as likely to have a >25% reduction in DLCO (35 vs 24%, P = 0.4) and 1.5 times as likely to receive <two-thirds of their planned doses (35 vs 24%, P = 0.4). Patients who received less than full doses of bleomycin had worse outcomes if they were of good or poor prognosis. 

Conclusion: Asymptomatic reductions in DLCO caused 20% of bleomycin doses to be omitted and 30% of patients to receive <two-thirds of their planned doses. A 25% reduction in DLCO appears too cautious a threshold. Given the potential negative impact of this practice on anti-cancer effect, routine use of PFT to monitor for bleomycin toxicity should be questioned.