A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer.
BACKGROUND
Despite considerable improvement in the treatment of advanced ovarian cancer, the optimization of efficacy and tolerability remains an important issue. Therefore, we performed a randomized, phase III non-inferiority trial comparing paclitaxel plus cisplatin (PT) with paclitaxel plus carboplatin (TC) in patients with advanced ovarian cancer.


METHODS
A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were randomly assigned to receive six courses of either PT or TC at 3-week intervals. The primary endpoint was the proportion of patients without progression at 2 years. Secondary endpoints included toxicity, response to treatment, quality of life, and overall and progression-free survival time. Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30, version 2.0. Survival curves were calculated using the Kaplan-Meier method, and hazard ratios were estimated using the Cox proportional hazards model.


RESULTS
The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms (40.0% for PT versus 37.5% for TC, difference = 2.5%, one-sided 95% confidence interval [CI] = - infinity to 8.2%). Median progression-free survival time in the TC arm (17.2 months, 95% CI = 15.2 to 19.3 months) and the PT arm (19.1 months, 95% CI = 16.7 to 21.5 months) were also not statistically significantly different; the same was true of median overall survival time (43.3 months, 95% CI = 37.2 to 47.8 months versus 44.1 months, 95% CI = 40.2 to 49.4 months, for the TC and PT arms, respectively). The TC regimen was associated with a higher frequency of hematologic toxicity, but a lower frequency of gastrointestinal and neurologic toxicity, than the PT regimen. Mean global quality-of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm (65.25 versus 51.97, respectively; difference = -13.28, 95% CI = -18.88 to -7.68).


CONCLUSIONS
The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life, and should, therefore, be considered as an important alternative for standard first-line chemotherapy in patients with advanced ovarian cancer.
du Bois
Andreas
A
Department of Gynecology and Gynecologic Oncology, Dr.-Horst-Schmidt-Kliniken, Wiesbaden, Germany. dubois.hsk-wiesbaden@uumail.de
Lück
Hans-Joachim
HJ
Meier
Werner
W
Adams
Hans-Peter
HP
Möbus
Volker
V
Costa
Serban
S
Bauknecht
Thomas
T
Richter
Barbara
B
Warm
Matthias
M
Schröder
Willibald
W
Olbricht
Sigrid
S
Nitz
Ulrike
U
Jackisch
Christian
C
Emons
Günther
G
Wagner
Uwe
U
Kuhn
Walther
W
Pfisterer
Jacobus
J
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005858:Germany; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010349:Patient Compliance; D016016:Proportional Hazards Models; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin