A Davidson1, A-S Veillard2, A Tognela2, M M K Chan2, B G M Hughes3, M Boyer4, K Briscoe5, S Begbie6, E Abdi7, C Crombie8, J Long9, A Boyce10, C R Lewis11, S Varma12, A Broad13, N Muljadi2, S Chinchen2, D Espinoza2, X Coskinas2, N Pavlakis14, M Millward15, M R Stockler2. 1. Department of Medical Oncology, Fiona Stanley Hospital, Perth andrew.davidson@health.wa.gov.au. 2. NHMRC Clinical Trials Centre, University of Sydney, Sydney. 3. Department of Medical Oncology, The Prince Charles Hospital, Brisbane School of Medicine, University of Queensland, Brisbane. 4. Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown. 5. Department of Medical Oncology, Coffs Harbour Health Campus, Coffs Harbour. 6. Department of Medical Oncology, Port Macquarie Base Hospital, Port Macquarie. 7. Department of Medical Oncology, The Tweed Hospital, Tweed Heads School of Medicine & Dentistry, Griffith University, Southport. 8. Department of Medical Oncology, Nepean Cancer Care Centre, Kingswood. 9. Department of Medical Oncology, Nambour General Hospital, Nambour. 10. Department of Medical Oncology, Lismore Base Hospital, Lismore. 11. Prince of Wales Hospital Clinical School, University of New South Wales, Randwick. 12. Department of Medical Oncology, The Townsville Hospital, Townsville. 13. Department of Medical Oncology, Geelong Hospital, Geelong. 14. Department of Medical Oncology, Royal North Shore Hospital, St Leonards. 15. Department of Medical Oncology, Sir Charles Gardiner Hospital, Nedlands School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
Abstract
BACKGROUND: We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. PATIENTS AND METHODS: Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. RESULTS: Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. CONCLUSION: The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.
BACKGROUND: We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. PATIENTS AND METHODS: Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. RESULTS: Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. CONCLUSION: The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.
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