Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site : results of an Italian multicenter, randomized, phase II study.
BACKGROUND
: To date, the standard treatment for patients who have carcinoma of unknown primary site has not been established.


METHODS
: In this randomized Phase II study, 66 previously untreated patients (33 patients per arm) with carcinomas of unknown primary site received cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) with either paclitaxel (70 mg/m2) or vinorelbine (25 mg/m2), and all drugs were administered intravenously on Days 1 and 8 of a 21-day cycle. Twenty-nine patients (44%) presented with > or =2 involved sites. The pathologic diagnosis was mainly adenocarcinoma (48 patients; 72.7%) and squamous carcinoma (7 patients; 10.6%).


RESULTS
: In the first arm, 16 patients (48.5%) experienced an objective response, and 9 patients (27.2%) had disease stabilization. In the vinorelbine-containing arm, 14 patients (42.3%) experienced an objective response, and 8 patients (24.2%) had disease stabilization. The median response duration and the median time to progression were similar in both treatment arms; the median overall survival was 9.6 months (95% confidence interval, 7.11-12.09 months) for patients who received the cisplatin/gemcitabine/paclitaxel regimen and 13.6 months (95% confidence interval, 6.61-20.59 months) for patients who received the vinorelbine combination. Grade 3 and 4 toxicities were more frequent in the paclitaxel-containing arm.


CONCLUSIONS
: Both combinations satisfied the 2-step design, demonstrating antitumor activity without relevant differences in response rates or response duration; however, the vinorelbine-containing regimen yielded superior results both in terms of overall survival (13.6 months vs 9.6 months) and in terms of treatment tolerability. Therefore, according to a pick the winner attitude, the combination of cisplatin/gemcitabine/vinorelbine may be considered in the design of future randomized, Phase III trials for patients with carcinomas of unknown primary site.
Palmeri
Sergio
S
Department of Oncology, Division of Medical Oncology, University of Palermo, Palermo, Italy. sergiopalmeri@alice.it
Lorusso
Vito
V
Palmeri
Laura
L
Vaglica
Marina
M
Porta
Camillo
C
Nortilli
Rolando
R
Ferraú
Francesco
F
Comella
Giuseppe
G
Massidda
Bruno
B
Danova
Marco
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007558:Italy; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D003841:Deoxycytidine; D014747:Vinblastine; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine