Phase Ib/II study of weekly topotecan and daily gefitinib in patients with platinum resistant ovarian, peritoneal, or fallopian tube cancer
| Autor: | Anca Chelariu-Raicu, John J. Kavanagh, Brian M. Slomovitz, Robert L. Coleman, Christopher Morrison, Diane C. Bodurka, Judith K. Wolf, David M. Gershenson, Charles F Levenback |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
medicine.medical_specialty medicine.drug_class Carcinoma Ovarian Epithelial Neutropenia Gastroenterology Drug Administration Schedule Tyrosine-kinase inhibitor 03 medical and health sciences 0302 clinical medicine Gefitinib Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Fallopian Tube Neoplasms Humans Prospective Studies Epidermal growth factor receptor Protein Kinase Inhibitors Aged 030304 developmental biology 0303 health sciences biology business.industry Obstetrics and Gynecology Cancer Middle Aged medicine.disease ErbB Receptors Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Fallopian tube cancer biology.protein Female Topotecan Neoplasm Recurrence Local Topoisomerase I Inhibitors business Progressive disease medicine.drug |
| Zdroj: | International Journal of Gynecologic Cancer. 30:1768-1774 |
| ISSN: | 1525-1438 1048-891X |
| DOI: | 10.1136/ijgc-2020-001863 |
| Popis: | Introduction50–70% of epithelial ovarian cancers overexpress epidermal growth factor receptor, and its expression has been correlated with poor prognosis. We conducted a phase Ib/II trial to examine the efficacy, safety, and toxicity of gefitinib, a tyrosine kinase inhibitor, combined with topotecan in women with recurrent ovarian cancer with epidermal growth factor receptor positivity.MethodsPatients with measurable recurrent or persistent cancer after treatment with a platinum containing regimen with positive epidermal growth factor receptor expression, as determined by immunohistochemistry, were eligible for the study. Initial treatment was 250 mg/day gefitinib (oral) and 2.0 mg/m2 topotecan (intravenous) on days 1, 8, and 15, on a 28 day cycle. Dose escalations were planned for topotecan (dose levels 1–3: 2, 3, and 4 mg/m2) until the maximum tolerated dose was reached.Results19 patients received a total of 61 cycles. Median age was 59.8 years (range 42–76 years). Histologic types in treated patients included 74% serous (n=14), 11% mixed (n=2), 11% transitional (n=2), and 5% clear cell (n=1). For phase Ib, three patients were treated at dose level 1, three at dose level 2, and three at dose level 3 for topotecan. The maximum tolerated dose was 4.0 mg/m2 (days 1, 8, and 15) for topotecan and 250 mg (daily) for gefitinib. Therefore, dose level 3 was used for phase II. Among the 19 patients, 63.2% (n=12) had progressive disease, 15.8% (n=3) had stable disease, 10.5% (n=2) had a partial response, and 10.5% (n=2) were not evaluable. The most serious adverse events of any grade attributed to the therapy were anemia (89.4%), neutropenia (68.4%), abdominal pain (84%), constipation (78.9%), and diarrhea (78.9%).ConclusionAlthough the drug combination was relatively well tolerated, this prospective phase Ib/II clinical trial did not show sufficient clinical activity of topotecan combined with gefitinib in patients with epidermal growth factor receptor positive recurrent ovarian, fallopian tube, or peritoneal cancers. |
| Databáze: | OpenAIRE |
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