A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study.
BACKGROUND
In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer.


METHODS
In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS).


RESULTS
151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients.


CONCLUSIONS
Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen. Electronic address: a.k.l.reyners@umcg.nl.
A K L
AKL
Reyners
Department of Research, Comprehensive Cancer Center The Netherlands, Utrecht.
L
L
de Munck
Department of Internal Medicine, Orbis Medical Center, Sittard.
F L G
FLG
Erdkamp
Department of Internal Medicine, Medical Spectrum Twente, Enschede.
W M
WM
Smit
Department of Medical Oncology, VU University Medical Center, Amsterdam.
K
K
Hoekman
Department of Medical Oncology, University Medical Center, Maastricht.
R I
RI
Lalisang
Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden.
H
H
de Graaf
Department of Internal Medicine, Medical Spectrum Twente, Enschede.
A N M
ANM
Wymenga
Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden.
M
M
Polee
Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen.
H
H
Hollema
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen.
M A T M
MATM
van Vugt
Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
M
M
Schaapveld
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen.
P H B
PHB
Willemse
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* / Q000009:adverse effects; D000077216:Carcinoma, Ovarian Epithelial; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D000068579:Celecoxib