Biweekly administration of irinotecan [CPT11] and 5-fluorouracil/folinic acid [5FU/FA] "De Gramont" as first line treatment in advanced or metastatic colorectal cancer [CRC]

ABSTRACT

The combination of CPT11, 5 fluorouracil and folinic acid "De Gramont" is now thought to be the 1st line chemotherapy for advanced or metastatic colorectal cancer. The aim of this study was to evaluate the efficacy and safety profile of the biweekly administration of CPT11 and 5FU/FA as 1[st] line treatment in patients with advanced or metastatic colorectal cancer. Patients with histologically confirmed advanced CRC, >1 measurable metastatic lesion. ECOG PS 0-1 and adequate bone marrow, renal and hepatic function were included. CPT11 [180mg/m[2] was administered on day 1 as 90 minutes infusion] and FA [200mg/m[2]] as 2 hour infusion followed by 5FU [400mg/m[2] bolus and 600mg/m[2] as 22 hours infusion] on days 1 and 2. This schedule was repeated every 2 weeks and each cycle consisted of 6 weeks for 6-9 cycles. Between October 2000 and December 2002, thirty patients were enrolled, M/F [20/10] with a median age of 48 years [40-60] and ECOG PS of 0-1. Primary tumor sites were colon [10 patients], rectum [15 patients], and colorectal [5 patients]. Tumor histology was adenocarcinoma, median number of involved sites was 2 [60% with 2 sites or more], liver [80%], lung [10%], lymph nodes [20%] and local recurrence [50%]. Previous treatment included palliative or radical surgery in 100% of cases, adjuvant chemotherapy in 12 patients [40%] and pelvic radiotherapy in 9 patients [30%]. A total of 235 cycles has been delivered with a median of 8 cycles/patient [6-9 cycles]. All patients were evaluable for toxicity, grade III toxicity was; neutropenia in 2 patients [6.6%], febrile neutropenia in one patient [3.3%] and diarrhea in one patient [3.3%]. Of the thirty patients evaluable, 3 patients [10%] achieved CR, 14 PR [46.6%] 7 SD [23.3%] and 6 patients progressed [20%] resulting in an overall response rate [ORR] of 56.6%. Median time to progression and survival was 12.5 and 21 months respectively. Median duration of response was 14.5 months. Biweekly administration of CPT11 and 5 FU/FA is an active and well tolerated regimen as first line treatment in patients with advanced or metastatic CRC with an ORR of 56.6%