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 (ANZUP)

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)893-898
    Number of pages6
    JournalInternal Medicine Journal
    Volume46
    Issue number8
    DOIs
    Publication statusPublished - 1 Aug 2016

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    Roncolato, F. T., Chatfield, M., Houghton, B., Toner, G., Stockler, M., Thomson, D., ... on behalf of the Australian and New Zealand Urogenital Prostate Cancer Trials Group (ANZUP) (2016). The effect of pulmonary function testing on bleomycin dosing in germ cell tumours. Internal Medicine Journal, 46(8), 893-898. https://doi.org/10.1111/imj.13158