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

F. T. Roncolato, M. Chatfield, B. Houghton, G. Toner, M. Stockler, D. Thomson, M. Friedlander, H. Gurney, M. Rosenthal, P. Grimison, on behalf of the Australian and New Zealand Urogenital Prostate Cancer Trials Group

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. There were 12 planned weekly bleomycin doses for intermediate-risk and poor-risk disease, and 9 for good-risk disease. Clinical assessments, chest x-ray, DLCO and FVC were done 2-weekly. Bleomycin was ceased for: predefined clinical/radiologic evidence of pulmonary toxicity; >25% reduction in DLCO or FVC. We determined doses planned, received, omitted; and patients receiving all, ≥2/3, <2/3 of planned bleomycin doses. Of 43 eligible patients, 30% had lung metastases. 375 of 471 (80%) of planned bleomycin doses were received; and 30% received <(2) /3 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 <(2) /3 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. Asymptomatic reductions in DLCO caused 20% of bleomycin doses to be omitted and 30% of patients to receive <(2) /3 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.