Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.

Abstract

PURPOSE:

Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit.

PATIENTS AND METHODS:

We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included <or= two lines of chemotherapy for recurrence. End points included response rate (via Response Evaluation Criteria in Solid Tumors [RECIST] or modified Gynecological Cancer Intergroup CA-125), toxicity, progression-free survival (PFS), and overall survival (OS).

RESULTS:

Forty-seven patients were enrolled; 46 were treated. Clinical benefit rate (defined as complete response [CR] or partial response [PR], stable disease [SD] > 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months.

CONCLUSION:

Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs.

• Authors: Ursula A Matulonis, Suzanne Berlin, Percy Ivy, Karin Tyburski, Carolyn Krasner, Corrine Zarwan, Anna Berkenblit, Susana Campos, Neil Horowitz, Stephen A Cannistra, Hang Lee, Julie Lee, Maria Roche, Margaret Hill, Christin Whalen, Laura Sullivan, Chau Tran, Benjamin D Humphreys, Richard T Penson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 33 Pg. 5601-6 (Nov 20 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19826113 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Quinazolines
• Receptors, Vascular Endothelial Growth Factor
• cediranib

Topics

• Administration, Oral
• Adult
• Aged
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Fallopian Tube Neoplasms (drug therapy, mortality, pathology)
• Female
• Humans
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, mortality, pathology)
• Neoplasms, Glandular and Epithelial (drug therapy, mortality, pathology)
• Ovarian Neoplasms (drug therapy, mortality, pathology)
• Peritoneal Neoplasms (drug therapy, mortality, pathology)
• Prognosis
• Quinazolines (administration & dosage, adverse effects)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors, therapeutic use)
• Risk Assessment
• Survival Analysis
• Treatment Outcome