Irinotecan hydrochloride (CPT-11) resistance identified by K-ras mutation in patients with progressive colon cancer after treatment with 5-fluorouracil (5-FU)

• Published in: American journal of clinical oncology Vol. 20; no. 5; pp. 527 - 529
• Main Authors: NEMUNAITIS, J, COX, J, MEYER, W, COURTNEY, A, MUES, G
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-10-1997
• Subjects: Adenine - analysis; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Chemotherapy; Codon - genetics; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Disease Progression; DNA, Neoplasm - analysis; DNA, Neoplasm - genetics; Drug Resistance, Neoplasm - genetics; Exons - genetics; Female; Fluorouracil - therapeutic use; Forecasting; Genes, ras - genetics; Guanine - analysis; Humans; Irinotecan; Male; Medical sciences; Middle Aged; Mutation - genetics; Pharmacology. Drug treatments; Prognosis; Retreatment; Sequence Analysis, DNA; Survival Rate; Thymine - analysis; Treatment Failure; Antineoplastic agent; Human; Drug combination; Intravenous administration; Fluoropyrimidine derivatives; Prediction; Tumoral marker; Malignant tumor; Survival; Colonic disease; Resistance; Irinotecan; Chemotherapy; Treatment; Tumor progression; Digestive diseases; Intestinal disease; Clinical trial; Drug interaction; Colon; Mutation; Onc gene; Fluorouracil
• ISSN: 0277-3732; 1537-453X
• DOI: 10.1097/00000421-199710000-00020

To determine the prognostic role of a K-ras mutation in tumor tissue of patients with refractory colon cancer who received irinotecan hydrochloride (CPT-11).
DNA was extracted from paraffin-stored tumor tissue of 35 patients with progressive colon cancer failing treatment with 5-fluorouracil who subsequently received CPT-11 (100 mg/m2 i.v. per week x 4 weeks with 2 weeks off per course). The first exon of the K-ras gene was amplified by polymerase chain reaction by using K-ras-specific primers followed by mutant enrichment sequencing. Survival differences of patients with a K-ras mutation were compared with those of patients with a normal K-ras status.
A total of 21 patients had a normal K-ras sequence and 14 patients had a K-ras mutation [GAT, n = 7; TGT, n = 3; and GCT, AGT, GTT, GAC (codon 13), n = 1 each]. Median survival of patients with a normal ras sequence from time of treatment with CPT-11 was 332 days compared with 169 days for patients with a K-ras mutation (p = 0.0036). No differences in age, sex, cancer stage, surgical treatment, or chemotherapy treatment were observed.
Determination of the presence of a K-ras mutation may predict survival in patients with progressive colon cancer after treatment with 5-fluorouracil who receive CPT-11.