Gefitinib in combination with tamoxifen in patients with ovarian cancer refractory or resistant to platinum-taxane based therapy--a phase II trial of the AGO Ovarian Cancer Study Group (AGO-OVAR 2.6).
BACKGROUND
Tamoxifen and gefitinib (IRESSA) combination therapy was studied in patients with ovarian cancer refractory or resistant to platinum- and taxane-based therapy.


METHODS
In this phase II study, 56 patients with epithelial ovarian carcinoma or cancer of the fallopian tube or peritoneum received oral tamoxifen 40 mg/day and gefitinib 500 mg/day until progression or unacceptable toxicity.


RESULTS
Seventeen patients (mean age: 59.6 years) had previously received first-line platinum/taxane treatment only, while 39 had received 2-8 (median 2) prior chemotherapy regimens. Gefitinib dose reduction to 250 mg/day was performed in 10 patients (14.9%), predominantly due to diarrhea (6 patients [10.7%]). Trial medication was discontinued in 6 patients (10.7%) due to adverse events (AEs). The most frequent drug-related AEs were diarrhea and acne-like skin rash. There were no tumor responses, but 16 patients had stable disease. Median time-to-progression was 58 days (95% CI, 55-71 days) and median survival was 253 days (95% CI, 137-355 days).


CONCLUSIONS
Gefitinib plus tamoxifen did not appear to be efficacious in the treatment of patients with refractory/resistant ovarian cancer. The addition of tamoxifen did not worsen the known side effects of gefitinib, or induce additional side effects.
Wagner
Uwe
U
Department of Gynecology, Gynecologic Endocrinology and Oncology, Philipps-University Marburg, Baldingerstrasse, D-35043 Marburg, Germany. uwe.wagner@med.uni-marburg.de
du Bois
Andreas
A
Pfisterer
Jacobus
J
Huober
Jens
J
Loibl
Sybille
S
Lück
Hans-Joachim
HJ
Sehouli
Jalid
J
Gropp
Martina
M
Stähle
Anne
A
Schmalfeldt
Barbara
B
Meier
Werner
W
Jackisch
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010349:Patient Compliance; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology
D001952:Bridged-Ring Compounds; D009944:Organoplatinum Compounds; D011799:Quinazolines; D043823:Taxoids; D013629:Tamoxifen; C080625:taxane; D000077156:Gefitinib