Prognostic implications of c-Ki-ras2 mutations in patients with advanced colorectal cancer treated with 5-fluorouracil and interferon

A study of the Eastern Cooperative Oncology Group (EST 2292)

Scott Wadler, Rajesh Bajaj, Donna Neuberg, Venita Agarwal, Hilda Haynes-Lewis, Al B. Benson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

PURPOSE: Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colerectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colerectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS: Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-α or IFN-β. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS: Seventy- two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS: It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.

Original languageEnglish (US)
Pages (from-to)284-288
Number of pages5
JournalCancer Journal from Scientific American
Volume3
Issue number5
StatePublished - Oct 9 1997

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Expressed Sequence Tags
Fluorouracil
Interferons
Colorectal Neoplasms
Mutation
Codon
Survival
Neoplasms
Mutation Rate
Tumor Biomarkers
Histology
Therapeutics
Retrospective Studies
Medicine
Polymerase Chain Reaction

Keywords

  • Colorectal cancer
  • Interferon
  • Ki-ras
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic implications of c-Ki-ras2 mutations in patients with advanced colorectal cancer treated with 5-fluorouracil and interferon : A study of the Eastern Cooperative Oncology Group (EST 2292). / Wadler, Scott; Bajaj, Rajesh; Neuberg, Donna; Agarwal, Venita; Haynes-Lewis, Hilda; Benson, Al B.

In: Cancer Journal from Scientific American, Vol. 3, No. 5, 09.10.1997, p. 284-288.

Research output: Contribution to journalArticle

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title = "Prognostic implications of c-Ki-ras2 mutations in patients with advanced colorectal cancer treated with 5-fluorouracil and interferon: A study of the Eastern Cooperative Oncology Group (EST 2292)",
abstract = "PURPOSE: Mutations in c-Ki-ras2 (ras) occur in about 40{\%} of patients with colerectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colerectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS: Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-α or IFN-β. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS: Seventy- two patients were enrolled in this trial. Mutations in ras were detected in 25 (35{\%}), including 17 (23{\%}) in codon 12, four (6{\%}) in codon 13, and four (6{\%}) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43{\%}) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32{\%}) and 15 of 41 nonresponders (37{\%}) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS: It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.",
keywords = "Colorectal cancer, Interferon, Ki-ras, Prognosis",
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T1 - Prognostic implications of c-Ki-ras2 mutations in patients with advanced colorectal cancer treated with 5-fluorouracil and interferon

T2 - A study of the Eastern Cooperative Oncology Group (EST 2292)

AU - Wadler, Scott

AU - Bajaj, Rajesh

AU - Neuberg, Donna

AU - Agarwal, Venita

AU - Haynes-Lewis, Hilda

AU - Benson, Al B.

PY - 1997/10/9

Y1 - 1997/10/9

N2 - PURPOSE: Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colerectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colerectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS: Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-α or IFN-β. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS: Seventy- two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS: It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.

AB - PURPOSE: Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colerectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colerectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS: Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-α or IFN-β. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS: Seventy- two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS: It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.

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KW - Interferon

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KW - Prognosis

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