Use of a multi-drug regimen gemcitabine, 5-fluorouracil, irinotecan, cisplatin, bevacizumab, docetaxel, and cyclophosphamide (GFIP/BDC) for heavily pretreated relapsed epithelial ovarian, fallopian tube and primary peritoneal cancer

BACKGROUND: Epithelial ovarian cancer has the highest fatality rate of all gynecologic malignancies. Although the majority of patients achieve complete clinical response after initial cytoreductive surgery and platinum-based chemotherapy, most recur and almost all will eventually acquire platinum-resistance for which treatment options become limited. The objective of the study was to describe response and tolerability of metronomic chemotherapy regimen GFIP/BDC, a modification of the G-FLIP regimen, in patients with persistent or recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer. METHODS: A retrospective descriptive analysis of 20 patients from a single academic institution who received combination GFIP/BDC therapy from January 1, 2011 to August 31, 2016 for persistent or recurrent EOC/FT/PP. Treatment consisted of a 2-day combination of gemcitabine 300 mg, 5-fluorouracil 500 mg/m2, irinotecan 20-30 mg/m2, cisplatin 20 mg/m2, bevacizumab 4 mg/kg, docetaxel 20 mg/m2, and cyclophosphamide 200 mg/m2 administered every 14 days. Toxicities were retrospectively graded using CTCAE v4.0. RESULTS: Twenty patients were identified with a median age 57.5 years (range 32–71). A total of 85% of patients were non-Hispanic white, 90% had cancer of high-grade serous histology, and all had a GOG performance status of 0–1. Patients had received a median of 3 prior regimens and 95% were platinum-resistant. Median number of cycles of GFIP/BDC administered was 9 (range 3–48) and patients remained on treatment for a median of 5.1 months (range 1.5–24). Eleven patients (55%) experienced a partial clinical response with a median duration of 6 months (range 1.5–20). Six patients (30%) survived progression free for at least 6 months. Ten patients (50%) experienced at least one grade 3/4 adverse event. Grade 3 adverse events were hematologic (n = 5), constitutional (n = 3), gastrointestinal (n = 3), neurologic (n = 2), and vascular (n = 1). There was only one grade 4 adverse event which was severe neutropenia. Patients discontinued treatment due to disease progression 65% (n = 13), toxicity 20% (n = 4), patient preference 10% (n = 2), and 5% (n = 1) is currently on treatment. CONCLUSIONS: Selected patients with epithelial ovarian, fallopian tube or primary peritoneal cancer who have failed multiple lines of conventional cytotoxic treatment may benefit from GFIP/BDC. Toxicity might be a limiting factor for administration.