Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer.
OBJECTIVE
One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.


METHODS
We performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m(2), respectively) with the same combination and additional gemcitabine 800 mg/m(2) on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.


RESULTS
Between 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).


CONCLUSIONS
The addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.
du Bois
Andreas
A
Department of Gynecology and Gynecologic Oncology, Dr Horst Schmidt Klinik, Ludwig-Erhard-Str 100, D-65199 Wiesbaden, Germany. prof.dubois@googlemail.com
Herrstedt
Jørn
J
Hardy-Bessard
Anne-Claire
AC
Müller
Hans-Helge
HH
Harter
Philipp
P
Kristensen
Gunnar
G
Joly
Florence
F
Huober
Jens
J
Avall-Lundqvist
Elisabeth
E
Weber
Béatrice
B
Kurzeder
Christian
C
Jelic
Svetislav
S
Pujade-Lauraine
Eric
E
Burges
Alexander
A
Pfisterer
Jacobus
J
Gropp
Martina
M
Staehle
Anne
A
Wimberger
Pauline
P
Jackisch
Christian
C
Sehouli
Jalid
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine