A phase 3 randomized trial of adding topical nitroglycerin to first line chemotherapy for advanced non–small-cell lung cancer: The Australasian Lung cancer Trials Group NITRO Trial
Mené sur 372 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de nitroglycérine topique à une chimiothérapie de première ligne à base de sels de platine
Background : We sought to determine if the substantial benefits of topical nitroglycerin with first line, platinum-based, doublet chemotherapy in advanced non–small-cell lung cancer (NSCLC) seen in a phase 2 trial could be corroborated in a rigorous, multicenter, phase 3 trial. Patients and methods : Patients starting one of five, pre-specified, 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 endpoint. 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 v 4.8 months, HR=1.07, 95% CI 0.86 to 1.32, P=0.55), overall survival (median 11.0 v 10.3 months, HR=0.99, 95% CI 0.79 to 1.24, P=0.94), or objective tumor response (31% v 30%, relative risk=1.03, 95% CI 0.82 to 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.