Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.
OBJECTIVE
New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC.


METHODS
Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days.


RESULTS
Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms.


CONCLUSIONS
This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.
Gatzemeier
U
U
Grosshansdorf Hospital, Grosshansdorf, Germany.
von Pawel
J
J
Gottfried
M
M
ten Velde
G P
GP
Mattson
K
K
de Marinis
F
F
Harper
P
P
Salvati
F
F
Robinet
G
G
Lucenti
A
A
Bogaerts
J
J
Gallant
G
G
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D016019:Survival Analysis
D000970:Antineoplastic Agents; D017239:Paclitaxel; D002945:Cisplatin