Back to Search
Start Over
Phase Ib/II study of weekly topotecan and daily gefitinib in patients with platinum resistant ovarian, peritoneal, or fallopian tube cancer
- Source :
- International Journal of Gynecologic Cancer. 30:1768-1774
- Publication Year :
- 2020
- Publisher :
- BMJ, 2020.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15251438 and 1048891X
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- International Journal of Gynecologic Cancer
- Accession number :
- edsair.doi.dedup.....599c76b16938b9ed883126978c7a1ebf