Phase II study of bevacizumab (B), camptosar (I), high-dose 24-hour continuous intravenous infusion of floxuridine (F) and leucovorin (L) in patients with previously untreated metastatic colon cancer. (B-IFL)

Abstract

e15114 Background: In a previous study, IFL was used in patients (pt) with untreated metastatic colon cancer and a median overall survival (MOS) of 31 months (m). In the current study we added B to IFL to determine toxicity profiles (TP) and the response rate (RR) to the B-IFL regimen. The primary end-point is MOS Methods: Each cycle involved 6 weeks (wks) of treatment. The treatment cycle consisted of a 90 minute infusion of I (110 mg/m2), followed by a 24 hour infusion of F (120mg/kg) and L (500 mg/m2) on wks 1, 2, 4, 5. Pt received B (7.5mg/kg) over 90 minutes on wks 1 and 4 prior to IFL. No therapy was given on wks 3 and 6. Eligible pt received 2 cycles of B-IFL followed by CT scan. Quality of life data and thymidylate synthase expression in peripheral blood mononuclear cells was monitored Results: 22 pt with a median age of 57 (38–82), 11 males and 11 females were enrolled. Median KPS was 90% (50–100). 8 pt (36%) had bilobar liver disease and involvement of 1 other organ, 6 pt (27%) had bilobar liver disease with involvement of ≥ 2 other organs; 5 pt (23.5%) had bilobar liver disease; 2 pt (9%) had abdominal carcinomatosis; 1 pt (4.5 %) had involvement in one liver lobe. Grade (Gr) 4 toxicity: pulmonary embolus 1 pt (5%) incidental CT finding. Gr 3 occurred in 11 pt (50%); DVT, diarrhea (Drh) 3 pt (14%); fatigue (Ftg), infection, port site thrombosis (Pst), small bowel obstruction 2 pt (9%); wound dehiscence 1pt (5%); Gr 2 and 1: constipation; Drh; Ftg; nausea; neutropenia; Pst; alopecia; anorexia; mucositis. 17 pt remain alive with median follow up of 15 m (2–28). 5 pt have died due to progression of disease. The estimated median time to progression was 13 m with corresponding lower 95% confidence bound of 8.4 m. Kaplan-Meier estimate at 2 yr survival is 61% (95% CI 27–83%). RR in 21 pt was 67% (95% CI: 43–85%). Conclusions: B-IFL regimen has a manageable TP. RR and progression free interval were promising. Pt accrual is ongoing. Supported by Pfizer. No significant financial relationships to disclose.