Standard
chemotherapy in advanced
colorectal carcinoma (CRC) has not yet been established. The present study was conducted to assess the efficacy and toxicity profile of
CPT-11,
leucovorin (LV), and bolus
5-fluorouracil (5-FU) in a weekly schedule. Fifty-five patients were entered with no prior
chemotherapy for advanced disease or adjuvant treatment ended at least 6 months preceding study entry, and 45 were assessable for response. Patients were treated with
CPT-11 80 mg/m2 (7 patients) or 70 mg/m2 (48 patients). After completion of
CPT-11 infusion, LV 200 mg/m2 was administered over 2 hr followed immediately by
5-FU 450 mg/m2, IV bolus, weekly for 6 weeks followed by a 2-week rest period. Treatment was continued for four cycles. Because of grade 3 and 4
diarrhea in four of the first seven patients, the study was amended to reduce the starting dose of
CPT-11 from 80 to 70 mg/m2 weekly. Four complete and 10 partial responses were observed (response rate: 25.5%), the median time to progression (
TTP) was 7.7 months, 1-year survival rate was 62.3%, and the median overall survival was 15.0 months. Grade 3 and 4
diarrhea occurred in seven patients (12.7%), four of them treated with
CPT-11 80 mg/m2. Grade 3 myelotoxicity occurred in five patients (9.0%). Toxic death because of
diarrhea,
neutropenia,
bacteremia, and
sepsis occurred in a patient treated with
CPT-11 80 mg/m2. Our results confirm the efficacy of
CPT-11, LV, and
5-FU in a weekly schedule in patients with advanced CRC. Further studies are needed to compare the present regimen with higher doses of
CPT-11 with LV plus different schedules of
5-FU administration in the treatment of metastatic CRC.