A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial

• Published in: Annals of oncology Vol. 26; no. 11; pp. 2280 - 2286
• Main Authors: Davidson, A., Veillard, A.-S., Tognela, A., Chan, M.M.K., Hughes, B.G.M., Boyer, M., Briscoe, K., Begbie, S., Abdi, E., Crombie, C., Long, J., Boyce, A., Lewis, C.R., Varma, S., Broad, A., Muljadi, N., Chinchen, S., Espinoza, D., Coskinas, X., Pavlakis, N., Millward, M., Stockler, M.R., Hughes, Brett, Boyer, Michael, Briscoe, Karen, Davidson, Andrew, Begbie, Stephen, Abdi, Ehtesham, Crombie, Catherine, Long, Jeremy, Jasas, Kevin, Lewis, Craig, Boyce, Adam, Vama, Suresh, Broad, Adam, Broaddge, Vy, Gibbs, David, Blum, Robert, McLachlan, Sue-Anne, Haydon, Andrew, Bray, Victoria, Vardy, Janette, Mallesara, Girish, Lowenthal, Ray, Asghari, Ray, Tiley, Susan, Hayes, Theresa, Islam, Mohammed, Ackland, Steven, Adams, Jacqui, Pavlakis, Nick, Stockler, Martin, Muljadi, Nick, Coskinas, Xanthi, Chinchen, Sarah, Chan, Matthew, Tognela, Annette, Ferraro, Danielle, Cosman, Rasha
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2015
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Australia - epidemiology; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - epidemiology; chemotherapy; Female; Follow-Up Studies; Humans; lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - epidemiology; Male; Middle Aged; nitroglycerin; Nitroglycerin - administration & dosage; phase III clinical trial; Australia; lung cancer; phase III clinical trial; nitroglycerin; chemotherapy
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdv373

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 starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. 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. The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.