IRINOTECAN HYDROCHLORIDE (CPT-11) RESISTANCE IDENTIFIED BY K-RAS MUTATION IN PATIENTS WITH PROGRESSIVE COLON-CANCER AFTER TREATMENT WITH 5-FLUOROURACIL (5-FU)

Objective: To determine the prognostic role of a K-ras mutation in tum or tissue of patients with refractory colon cancer who received irinot ecan hydrochloride (CPT-11). Methods: DNA was extracted from paraffin- stored tumor tissue of 3.4 patients with progressive colon cancer fail ing treatment with 5-fluorouracil who subsequently received CPT-11 (10 0 mg/m(2) i.v, per week x 4 weeks with 2 weeks off per course). The fi rst exon of the K-ras gene was amplified by polymerase chain reaction by using K-ras-specific primers followed by mutant enrichment sequenci ng. Survival differences of patients with a K-rns mutation were compar ed with those of patients with a normal K-rns status. Results: A total of 21 patients had a normal K-ras sequence and 14 patients had a K-ms mutation [GAT, it = 7; TGT, ii = 3; and GCT, AGT, GTT, GAC (codon 13) , n = 1 each]. Median survival of patients with a normal ms sequence f rom time of treatment with CPT-11 was 332 days compared with 169 days for patients with a K-ras mutation (p = 0.0036). Mo differences in age , sex, cancer stage, surgical treatment, or chemotherapy treatment wer e observed. Conclusion: Determination of the presence of a K-ms mutati on may predict survival in patients with progressive colon cancer afte r treatment with 5-fluorouracil who receive CPT-11.