scholarly journals Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX STUDY involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer

2015 ◽  
Vol 112 (6) ◽  
pp. 963-970 ◽  
Author(s):  
T J Price ◽  
M A Bruhn ◽  
C K Lee ◽  
J E Hardingham ◽  
A R Townsend ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitomycin C ◽  
Gene Mutation ◽  
Advanced Colorectal Cancer ◽  
Phase Iii ◽  
Mutation Status ◽  
Pik3ca Gene

Impact of KRAS and BRAF Gene Mutation Status on Outcomes From the Phase III AGITG MAX Trial of Capecitabine Alone or in Combination With Bevacizumab and Mitomycin in Advanced Colorectal Cancer

2011 ◽  
Vol 29 (19) ◽  
pp. 2675-2682 ◽  
Author(s):  
Timothy J. Price ◽  
Jennifer E. Hardingham ◽  
Chee K. Lee ◽  
Andrew Weickhardt ◽  
Amanda R. Townsend ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Gene Mutation ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Braf Gene ◽  
Kras Gene ◽  
Mutation Status

Purpose Mutations affecting the KRAS gene are established predictive markers of outcome with anti–epithelial growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC). The relevance of these markers for anti–vascular endothelial growth factor (VEGF) therapy is controversial. This analysis was performed to assess the predictive and prognostic impact of KRAS and BRAF gene mutation status in patients receiving capecitabine with bevacizumab (CG) or capecitabine without bevacizumab in the phase III AGITG MAX (Australasian Gastrointestinal Trials Group MAX) study. Patients and Methods Mutation status was determined for 315 (66.9%) of the original 471 patients. Mutation status was correlated with efficacy outcomes (response rate, progression-free survival [PFS], and overall survival [OS]), and a predictive analyses was undertaken. Results Mutations in KRAS and BRAF genes were observed in 28.8% and 10.6% of patients, respectively. KRAS gene mutation status (wild type [WT] v mutated [MT]) had no prognostic impact for PFS (hazard ratio [HR], 0.89; CI, 0.69 to 1.14) or OS (HR, 0.97; CI, 0.73 to 1.28). BRAF mutation status (WT v MT) was not prognostic for PFS (HR, 0.80; CI, 0.54 to 1.18) but was prognostic for OS (HR, 0.49; CI, 0.33 to 0.73; P = .001). By using the comparison of capecitabine versus capecitabine and bevacizumab (CB) and CB plus mitomycin (CBM), KRAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS (test for interaction P = .95 and 0.43, respectively). Similarly, BRAF gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS (test for interaction P = .46 and 0.32, respectively). Conclusion KRAS gene mutation status was neither prognostic for OS nor predictive of bevacizumab outcome in patients with advanced CRC. BRAF gene mutation status was prognostic for OS but was not predictive of outcome with bevacizumab.

Analysis of PTEN in patients with advanced colorectal cancer (CRC) receiving capecitabine alone or in combination with bevacizumab with or without mitomycin C in the phase III AGITG MAX trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3534-3534
Author(s):  
Timothy Jay Price ◽  
Jenny Hardingham ◽  
Chee Lee ◽  
Joe Wrin ◽  
Amanda Rose Townsend ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitomycin C ◽  
Copy Number ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Phase Iii ◽  
Pten Loss ◽  
Anti Vegf

3534 Background: There is an urgent need for potential biomarkers for anti-VEGF therapies. The tumour suppressor gene PTEN is thought to have a potential role as a biomarker for anti-EGFR therapy in CRC, but there is also evidence that decreased levels of PTEN leads to increased expression of VEGF suggesting a potential relationship to outcome with anti-VEGF therapy*. The prognostic value of PTEN also remains controversial. Methods: Patients enrolled in the Phase III MAX trial of capecitabine (C) +/- bevacizumab (B) (+/- mitomycin C (M)) with available tissue were analysed for PTEN expression (loss v no loss) as assessed using a Taqman copy number assay to measure copy number variation at the PTEN locus. PTEN status was correlated with progression-free survival (PFS) and overall survival (OS) outcomes. The predictive value of PTEN status for bevacizumab efficacy was also examined. Results: Of the original 471 patients enrolled in the trial, tissue from 302 (64.1%) patients were analysed. Baseline characteristics of those with and without tissue were comparable. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation. Patients with PTEN loss were more likely to have rectal primary (p=0.01) and less likely to have lung metastasis (p=0.03). By using the comparison of C v CB+CBM, PTEN status was not significantly predictive of the effectiveness of B for PFS or OS (Table). PTEN status is also not prognostic for PFS or OS in multivariate analyses adjusting for other baseline factors (Table). Conclusions: PTEN status did not significantly predict different benefit with anti-VEGF therapy. PTEN status was also not prognostic for survival in advanced colorectal cancer. [Table: see text]

Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

scholarly journals Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer

2017 ◽  
Vol 18 (9) ◽  
pp. 694-704 ◽  
Author(s):  
Avital Lev ◽  
Safoora Deihimi ◽  
Elena Shagisultanova ◽  
Joanne Xiu ◽  
Amriti R. Lulla ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitomycin C ◽  
Advanced Colorectal Cancer

Predictive and prognostic markers for the outcome of chemotherapy in advanced colorectal cancer, a retrospective analysis of the phase III randomised CAIRO study

2009 ◽  
Vol 45 (11) ◽  
pp. 1999-2006 ◽  
Author(s):  
Miriam Koopman ◽  
Sabine Venderbosch ◽  
Harm van Tinteren ◽  
Marjolijn J. Ligtenberg ◽  
Iris Nagtegaal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Retrospective Analysis ◽  
Advanced Colorectal Cancer ◽  
Prognostic Markers ◽  
Phase Iii

scholarly journals Continuous infusion fluorouracil/leucovorin and bolus mitomycin-C as a salvage regimen for patients with advanced colorectal cancer

Cancer ◽  
1995 ◽  
Vol 75 (3) ◽  
pp. 769-774 ◽  
Author(s):  
John A. Conti ◽  
Nancy E. Kemeny ◽  
Leonard B. Saltz ◽  
A. McKenzie André ◽  
Dennis D. Grossano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Continuous Infusion ◽  
Mitomycin C ◽  
Advanced Colorectal Cancer ◽  
Salvage Regimen
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