Phase Ib/II study of weekly topotecan and daily gefitinib in patients with platinum resistant ovarian, peritoneal, or fallopian tube cancer

Int J Gynecol Cancer. 2020 Nov;30(11):1768-1774. doi: 10.1136/ijgc-2020-001863. Epub 2020 Oct 9.

Abstract

Introduction: 50-70% 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.

Methods: Patients 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.

Results: 19 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%).

Conclusion: Although 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.

Trial registration: ClinicalTrials.gov NCT00317772.

Keywords: ovarian neoplasms.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • ErbB Receptors / drug effects
  • Fallopian Tube Neoplasms / drug therapy*
  • Female
  • Gefitinib / administration & dosage*
  • Gefitinib / adverse effects
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Topoisomerase I Inhibitors / administration & dosage*
  • Topoisomerase I Inhibitors / adverse effects
  • Topotecan / administration & dosage*
  • Topotecan / adverse effects

Substances

  • Protein Kinase Inhibitors
  • Topoisomerase I Inhibitors
  • Topotecan
  • ErbB Receptors
  • Gefitinib

Associated data

  • ClinicalTrials.gov/NCT00317772