Open Access

Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen

  • Authors:
    • Gemma Bruera
    • Katia Cannita
    • Aldo Victor Giordano
    • Roberto Vicentini
    • Corrado Ficorella
    • Enrico Ricevuto
  • View Affiliations

  • Published online on: April 4, 2014     https://doi.org/10.3892/ijo.2014.2369
  • Pages: 1820-1830
  • Copyright: © Bruera et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

First-line triplet chemotherapy plus bevacizumab (FIr-B/FOx) can improve efficacy of metastatic colorectal cancer (MCRC), KRAS wild-type and mutant. Prognostic relevance of KRAS genotype was evaluated in patients unfit for FIr-B/FOx, treated with conventional medical treatments. Consecutive MCRC patients not eligible for FIr-B/FOx regimen due to age (≥75 years) and/or comorbidities were treated with tailored conventional first-line treatments. KRAS codon 12/13 mutations were screened by direct sequencing. Activity and efficacy were evaluated and compared according to medical treatments, age (non-elderly and elderly ≥65 years), comorbidity stage (Cumulative Illness Rating Scale), metastatic extension (liver-limited and other/multiple metastatic), and KRAS genotype, using log-rank. Selected first line treatments were medical in 37 patients (92.5%), and surgical in 3 patients (7.5%). Medical treatment regimens: triplet, 18 (45%); doublet, 15 (37.5%); mono-therapy, 4 (10%). At median follow-up of 8 months, objective response rate (ORR) was 37%, median progression-free survival (PFS) 7 months, liver metastasectomies 8% (liver-limited disease 37.5%), median overall survival (OS) 13 months. Triplet regimens failed to significantly affect clinical outcome, compared to doublet. According to KRAS genotype, ORR, PFS and OS were, respectively: wild-type 50%, 8 months, 13 months; mutant 25%, 6 months, 9 months. KRAS genotype wild-type compared to mutant significantly affected PFS, while not OS. KRAS c.35 G>A mutation (G12D) significantly affected worse PFS and OS compared to wild-type and/or other mutations. KRAS genotype, specifically the c.35 G>A KRAS mutation, may indicate poor prognosis in MCRC patients unfit for intensive medical treatments.
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June-2014
Volume 44 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Bruera G, Cannita K, Giordano AV, Vicentini R, Ficorella C and Ricevuto E: Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen. Int J Oncol 44: 1820-1830, 2014.
APA
Bruera, G., Cannita, K., Giordano, A.V., Vicentini, R., Ficorella, C., & Ricevuto, E. (2014). Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen. International Journal of Oncology, 44, 1820-1830. https://doi.org/10.3892/ijo.2014.2369
MLA
Bruera, G., Cannita, K., Giordano, A. V., Vicentini, R., Ficorella, C., Ricevuto, E."Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen". International Journal of Oncology 44.6 (2014): 1820-1830.
Chicago
Bruera, G., Cannita, K., Giordano, A. V., Vicentini, R., Ficorella, C., Ricevuto, E."Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen". International Journal of Oncology 44, no. 6 (2014): 1820-1830. https://doi.org/10.3892/ijo.2014.2369