Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer

Abstract

Background: Combination therapy of irinotecan, folinic acid (FA) and 5-fluorouracil (5-FU) has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases.

Methods: A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2), L-FA (200 mg/m2) and 5-FU bolus (400 mg/m2) on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2). One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients.

Results: The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%). Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%), nausea/vomiting (12%), leucopenia (3%), neutropenia (9%) and mucositis (3%). The overall response rate was 31% (4 CR and 7 PR), with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively.

Conclusions: The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant protocols.

Figure 1

Overall survival. The time to progression (TTP) and overall survival (OS, in months) are plotted as Kaplan-Meier-curves. Overall survival is drawn as a continuous line, total progression free survival as a dotted curve. TTP and OS were 7 and 17 months, respectively.

Figure 2

Quality of life assessed by the QLQ-C30 questionnaire. Quality of life was assessed immediately after inclusion into the study and at least once during the course of treatment, using the standardized EORTC QLQ-C30 questionnaire, version 2. Overall scores range from 0 to 100, divided into several subsets such as physical ability, emotional feelings, nausea/vomiting, fatigue, pain or diarrhea. Higher scores on global health status and physical functioning and lower scores on symptom scales and emotional assessment indicate a better quality of life.