Anca Chelariu- Raicu, MD of MD Anderson Cancer Center speaks about the ASCO 2020 abstract Phase I/II study of weekly topotecan and gefitinib in patients with platinum-resistant ovarian, peritoneal, or fallopian tube cancer.
In several forms of cancer, the epidermal growth factor receptor (EGFR) is expressed. EGFR may be overexpressed by fifty to 70% of the epithelial ovary, and its expression has in many cases been associated with poor prognostic characteristics. While these tumors are chemosensitive to platinum-based treatment, they also establish chemoresistance. We conducted a phase I / II trial to investigate the effectiveness, efficacy, and toxicity of gefitinib, a tyrosine kinase inhibitor, combined with topotecan in women with recurrent ovarian cancer with EGFR positive receptor (1 + or greater).
This research was qualified (n = 19) for patients with detectable, recurrent or chronic cancer following treatment with a platinum and paclitaxel-containing regimen. In which a traditional 3 + 3 algorithm was used, we first used "run-in" dose escalation. The initial treatment was an oral dose of gefitinib 250 mg daily and a dose of topotecan of 2.0 mg / m2 on days 1, 8 and 15, repeated every 28 days. Topotecan dose escalations (dose levels 1-3: 2, 3, 4 mg / m2) were anticipated before the MTD was reached. The Phase II research then included an additional 10 patients with refractory or advanced ovarian cancer.
19 patients obtained 61 cycles in total. The median age was 60. 73 per cent serous (n = 14), 12.5 per cent mixed (n = 2), 12.5 per cent transitional (n = 2) and 6.3 per cent clear cell (n = 1) were the histological forms of treated patients. Three patients were treated at dose level 1, three at dose level 2, and three at dose level 3. The median tolerated dose was 4.0 mg / m2 of topotecan on IV days 1, 8 and 15, and 250 mg p.o. of gefitinib. x28 days QD. Therefore, for the Phase II section of the experiment, dose level 3 was used. Of the 19 patients included in phase I / II, the response to therapy due to toxicity, missed therapy or reduced success status was invaluable for 3 patients. Of the 16 patients, 81% (n = 13) had a progressive disease, 12.5% had a stable disease (n = 2), and 6% had a partial response (n = 1). All 19 patients were evaluated for adverse effects; 60 percent had grade 3 treatment-related effects, mostly blood disorders such as anemia (n = 3, 16 percent), reduced neutrophil counts (n = 4, 21 percent).
In patients with EGFR-positive recurrent ovarian, fallopian tube, or peritoneal cancers, this prospective phase I / II clinical trial did not demonstrate adequate clinical activity of topotecan in combination with gefitinib. In this cohort, the drug mixture was reasonably well-tolerated. As such, due to the lack of response, the analysis did not progress to the next accrual objective. Details about the clinical trial: NCT003177722