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 tumor tissue of patients with refractory colon cancer who received irinotecan hydrochloride (CPT-11).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nemunaitis
J
J
Physician Reliance Network, Inc., Dallas, Texas, USA.
Cox
J
J
Meyer
W
W
Courtney
A
A
Mues
G
G
D000225:Adenine / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003062:Codon / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005544:Forecasting; D011905:Genes, ras / Q000235:genetics*; D006147:Guanine / Q000032:analysis; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D019233:Retreatment; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D013941:Thymine / Q000032:analysis; D017211:Treatment Failure
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003062:Codon; D004273:DNA, Neoplasm; D006147:Guanine; D000077146:Irinotecan; D000225:Adenine; D013941:Thymine; D005472:Fluorouracil; D002166:Camptothecin