title: Prognostic role of K-ras in patients with progressive colon cancer who received treatment with Marimastat (BB2516).
abstract: We determined the prognostic role of K-ras mutation in tumor tissue of patients with refractory colon cancer who received Marimastat (BB2516). DNA was extracted from paraffin-stored tumor tissue of 27 patients who previously failed 5-fluorouracil and were treated with BB2516. The presence of K-ras mutation was characterized by Polymerase Chain Reaction using ras- and p53-specific primers. ras and p53 oncoprotein expression was analyzed by an automated biotin-avidin immunoproxidase technique. Seventeen patients had a normal K-ras sequence and 10 patients had a K-ras mutation. Median survival of patients with a normal ras sequence was 330 days from the time of BB2516 treatment compared with 160 days for patients with a K-ras mutation (p = 0.0442, Wilcoxon; 0.0130 Log-Rank). No differences in age, sex, cancer stage, surgical treatment, or chemotherapy treatment were observed. Abnormalities involving ras expression did not affect survival. By comparison, median survival for patients with p53 mutation or p53 overexpression was both 158 days after BB2516 treatment. Patients having both K-ras and p53 mutations had the poorest median survival of 113 days (p = 0.035). There is a suggestion by univariate analysis that the presence of a K-ras mutation may predict survival in patients with progressive colon cancer. Further assessment with larger patient numbers and multivariate analysis is indicated.
authors.affiliation: PRN Research, Inc., Dallas, Texas, USA.
authors.forename: J
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: J
authors.initials: J
authors.lastname: Cox
authors.forename: S
authors.initials: S
authors.lastname: Hays
authors.forename: W
authors.initials: W
authors.lastname: Meyer
authors.forename: R
authors.initials: R
authors.lastname: Kebart
authors.forename: N
authors.initials: N
authors.lastname: Ognoskie
authors.forename: A
authors.initials: A
authors.lastname: Courtney
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Tong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D017422:Sequence Analysis, DNA; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat