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.
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.


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.


CONCLUSIONS
The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further.


BACKGROUND
Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.
Department of Medical Oncology, Fiona Stanley Hospital, Perth andrew.davidson@health.wa.gov.au.
A
A
Davidson
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
A-S
AS
Veillard
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
A
A
Tognela
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
M M K
MM
Chan
Department of Medical Oncology, The Prince Charles Hospital, Brisbane School of Medicine, University of Queensland, Brisbane.
B G M
BG
Hughes
Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown.
M
M
Boyer
Department of Medical Oncology, Coffs Harbour Health Campus, Coffs Harbour.
K
K
Briscoe
Department of Medical Oncology, Port Macquarie Base Hospital, Port Macquarie.
S
S
Begbie
Department of Medical Oncology, The Tweed Hospital, Tweed Heads School of Medicine & Dentistry, Griffith University, Southport.
E
E
Abdi
Department of Medical Oncology, Nepean Cancer Care Centre, Kingswood.
C
C
Crombie
Department of Medical Oncology, Nambour General Hospital, Nambour.
J
J
Long
Department of Medical Oncology, Lismore Base Hospital, Lismore.
A
A
Boyce
Prince of Wales Hospital Clinical School, University of New South Wales, Randwick.
C R
CR
Lewis
Department of Medical Oncology, The Townsville Hospital, Townsville.
S
S
Varma
Department of Medical Oncology, Geelong Hospital, Geelong.
A
A
Broad
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
N
N
Muljadi
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
S
S
Chinchen
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
D
D
Espinoza
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
X
X
Coskinas
Department of Medical Oncology, Royal North Shore Hospital, St Leonards.
N
N
Pavlakis
Department of Medical Oncology, Sir Charles Gardiner Hospital, Nedlands School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
M
M
Millward
NHMRC Clinical Trials Centre, University of Sydney, Sydney.
M R
MR
Stockler
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001315:Australia / Q000453:epidemiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*
D005996:Nitroglycerin
chemotherapy; lung cancer; nitroglycerin; phase III clinical trial