Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens.
OBJECTIVE
Despite the progress that has been achieved, long-term survival rates in patients with advanced ovarian cancer are still disappointing. One attempt to improve results could be the addition of non-cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines were among the candidates for incorporation as a third drug into first-line regimens.


METHODS
We performed a prospectively randomized phase III study comparing carboplatin-paclitaxel (TC; area under the curve 5/175 mg/m2, respectively) with epirubicin 60 mg/m2 added to the same combination (TEC) in previously untreated patients with advanced epithelial ovarian cancer. All drugs were administered intravenously on day 1 of a 3-week schedule for a planned minimum of six courses.


RESULTS
Between November 1997 and February 2000, 1,282 patients were randomly assigned to receive either TC (635 patients) or TEC (647 patients), respectively. Grade 3/4 hematologic and some nonhematologic toxicities (nausea/emesis, mucositis, and infections) occurred significantly more frequently in the TEC arm. Accordingly, quality-of-life analysis showed inferiority of TEC versus TC. Median progression-free survival time was 18.4 months for the TEC arm and 17.9 months for the TC arm (hazard ratio [HR], 0.95; 95% CI, 0.83 to 1.07; P = .3342). Median overall survival time was 45.8 months for the TEC arm and 41.0 months for the TC arm (HR, 0.93; 95% CI, 0.81 to 1.08; P = .3652). Similar nonsignificant differences were observed when strata were analyzed separately.


CONCLUSIONS
Addition of epirubicin to TC did not improve survival or time to treatment failure in patients with advanced epithelial ovarian cancer; therefore, it cannot be recommended for clinical use in this population.
du Bois
Andreas
A
Department of Gynecology & Gynecologic Oncology, HSK Dr Horst Schmidt Klinik Wiesbaden, Wiesbaden, Germany. dubois.hsk-wiesbaden@uumail.de
Weber
Beatrice
B
Rochon
Justine
J
Meier
Werner
W
Goupil
Alain
A
Olbricht
Sigrid
S
Barats
Jean-Claude
JC
Kuhn
Walther
W
Orfeuvre
Hubert
H
Wagner
Uwe
U
Richter
Barbara
B
Lueck
Hans-Joachim
HJ
Pfisterer
Jacobus
J
Costa
Serban
S
Schroeder
Willibald
W
Kimmig
Rainer
R
Pujade-Lauraine
Eric
E
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005602:France; D005858:Germany; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010349:Patient Compliance; D011446:Prospective Studies; D016019:Survival Analysis; D013997:Time Factors; D017211:Treatment Failure
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D016190:Carboplatin; D017239:Paclitaxel