Biweekly alternating FOLFOX and FOLFIRI in patients with previously untreated, advanced colorectal cancer (ACC): Updated results

Abstract

3563 Background: Irinotecan (CPT-11) and oxaliplatin (L-OHP) are active agents in ACC. Combining each with continuous infusion (CI) 5-fluorouracil (5-FU) provides an objective response rate approaching 50%, with acceptable toxicity in first line treatment. The objective of this study was to assess the efficacy and tolerance of a protocol that alternates Gramont's LV5FU2 schedule plus L-OHP (FOLFOX-4) with the same 5-FU regimen plus CPT-11 (FOLFIRI) on a biweekly basis. Methods: Patients with previously untreated, histologically confirmed, unresectable ACC were included if they had measurable disease; adequate bone marrow, liver, and renal functions; PS (ECOG) 0–2; life expectancy > 3 months, and written informed consent. Treatment consisted of 2-hours CI Folinic acid (FA) 200 mg/m2, bolus 5-FU 400 mg/m2 and 22-hours CI 5-FU 600 mg/m2, all on days 1 and 2 every 14 days. CPT-11 (180 mg/m2) and L-OHP (85 mg/m2) were given on day 1 of alternating chemotherapy administrations. 1 chemotherapy cycle (FOLFOX-FOLFIRI) takes 28 days. Response evaluation was scheduled every 3 cycles. Results: 79 patients were enrolled (42 males, 37 females). Median age was 61 years (range 39–77). On PS, patients were distributed as follows: 0 (43.8%), 1 (47.5%), and 2 (8.8%). The number of metastatic sites was 1 (39.7%) or >1 (60.3%). 745 infusions were administered in 77 patiens who were evaluable for toxicity (median 5 cycles per patient, range 1–9 cycles). Response evaluation was performed in 45 patients. 8.9% of patients showed a complete response and 51.1% showed a partial response. Disease was stabilized in 15.6% of patients and in 24.4% of patients disease progression was observed. Of the 77 patients evaluated for toxicity, 47.5% had grade 3–4 toxicity. The most common grade 3–4 adverse events were: neutropenia 28.9%, diarrhea 21.1%, pain 6.6%, leucopenia 5.3%, anemia 5.3%, asthenia 3.9%, infection 2.6%, febrile neutropenia 2.6%, nausea/vomiting 2.6%, neurotoxicity 1.3% and transaminase increase 1.3%. Conclusions: The updated results of this study suggest that this regimen is effective and shows a good safety profile. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Prasfarma/Almirall