Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers.
OBJECTIVE
To evaluate the efficacy and tolerability of imatinib mesylate (Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) in patients with recurrent ovarian and primary peritoneal cancer.


METHODS
This was an open-label, single-institution phase II trial. Patients were eligible if they had measurable platinum/taxane-resistant disease, received 2-4 prior treatment regimens, and over-expressed at least one imatinib target (c-Kit, PDGFR-beta, or c-Abl) by immunohistochemistry. Imatinib was administered orally at 600 mg daily for 6 weeks (one course) and was repeated in the absence of measurable progression.


RESULTS
Sixteen enrolled patients were evaluable for toxicity and 12 for response. The median number of prior treatments was 4. A total of 29 courses were initiated. No complete or partial responses were documented during a median follow-up of 6.6 months. However, 4 (33%) of the 12 evaluable patients had stable disease lasting 3.8, 6.4, 7.5, and 8+ months. Expression of PDGFR-beta and c-Abl was seen in 15 (94%) and c-Kit in 8 (50%) patients' tumors. There was no relationship between best response (stable disease) and target expression. Adverse events were uncommon, with fatigue and nausea/vomiting being reported in 34% and 31% of cycles, respectively. Two patients underwent dose reduction for rash and edema (n = 1) and grade 3 neutropenia (n = 1). No grade 4 toxicity was observed.


CONCLUSIONS
Imatinib mesylate was well tolerated but did not produce clinical responses in patients with previously treated metastatic ovarian and primary peritoneal carcinoma.
Coleman
Robert L
RL
Department of Gynecologic Oncology, Pathology, and Gynecologic Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. rcoleman@mdanderson.org
Broaddus
Russell R
RR
Bodurka
Diane C
DC
Wolf
Judith K
JK
Burke
Thomas W
TW
Kavanagh
John J
JJ
Levenback
Charles F
CF
Gershenson
David M
DM
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D043823:Taxoids / Q000494:pharmacology
D000970:Antineoplastic Agents; D001549:Benzamides; D009944:Organoplatinum Compounds; D010879:Piperazines; D011743:Pyrimidines; D043823:Taxoids; D000068877:Imatinib Mesylate