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.