Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small-cell lung cancer.
OBJECTIVE
To investigate the efficacy and safety of nitroglycerin plus vinorelbine and cisplatin in patients with previously untreated stage IIIB/IV non-small-cell lung cancer (NSCLC) as the experimental arm for the next phase III trial.


METHODS
One hundred twenty patients with stage IIIB/IV NSCLC were randomly assigned to vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1, with transdermally applied nitroglycerin (25 mg/patient daily for 5 days; arm A) or with placebo patch (arm B) every 3 weeks for a maximum of four cycles in a double-blind and controlled trial. Primary efficacy end points were the best confirmed response rate and time to disease progression (TTP).


RESULTS
The response rate in arm A (72%; 43 of 60 patients) was significantly higher than that for patients in arm B (42%; 25 of 60 patients; P < .001). Median TTP in arm A was longer than that in arm B (327 v 185 days). No severe adverse effect was recognized for either arm. The rate of grade 1 to 2 headache in arm A (30%; 18 of 60 patients) was significantly higher than that in arm B (2%; one of 60 patients; P < .001, chi(2) test).


CONCLUSIONS
Use of nitroglycerin combined with vinorelbine and cisplatin may improve overall response and TTP in patients with stage IIIB/IV NSCLC. The arm A regimen is being evaluated in a large phase III trial.
Yasuda
Hiroyasu
H
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Japan. yasuda@geriat.med.tohoku.ac.jp
Yamaya
Mutsuo
M
Nakayama
Katsutoshi
K
Sasaki
Takahiko
T
Ebihara
Satoru
S
Kanda
Akio
A
Asada
Masanori
M
Inoue
Daisuke
D
Suzuki
Tomoko
T
Okazaki
Tatsuma
T
Takahashi
Hidenori
H
Yoshida
Motoki
M
Kaneta
Tomohiro
T
Ishizawa
Kota
K
Yamanda
Shinsuke
S
Tomita
Naoki
N
Yamasaki
Miyako
M
Kikuchi
Akiko
A
Kubo
Hiroshi
H
Sasaki
Hidetada
H
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D005996:Nitroglycerin / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D014747:Vinblastine; D005996:Nitroglycerin; D002945:Cisplatin; D000077235:Vinorelbine