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



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.



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.
Department of Medical Oncology, NHMRC Clinical Trials Centre, Sydney, New South Wales, Australia.
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FT
Roncolato
Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
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M
Chatfield
Department of Medical Oncology, North Coast Cancer Institute, Port Macquarie, New South Wales, Australia.
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B
Houghton
Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, Victoria, Australia.
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G
Toner
Department of Medical Oncology, NHMRC Clinical Trials Centre, Sydney, New South Wales, Australia.|Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
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Stockler
Department of Medical Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
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Thomson
Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
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Friedlander
Department of Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
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H
Gurney
Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
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M
Rosenthal
Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.|Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.
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Grimison
D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001315:Australia; D001761:Bleomycin / Q000008:administration & dosage* / Q000009:adverse effects; D002248:Carbon Monoxide / Q000032:analysis; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000556:secondary; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D013902:Radiography, Thoracic; D012129:Respiratory Function Tests; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014797:Vital Capacity; D055815:Young Adult
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D005047:Etoposide; D002248:Carbon Monoxide; D002945:Cisplatin
bleomycin; germ cell tumour; pulmonary function testing