Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease
<p>Abstract</p> <p>Background</p> <p>Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of metastatic colorectal cancer (MCRC), particularly integrated with secondary liver surgery in liver-limited (L-L) patients. The prognostic va...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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BMC
2012-11-01
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| Series: | BMC Medicine |
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| Online Access: | http://www.biomedcentral.com/1741-7015/10/135 |
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| author | Bruera Gemma Cannita Katia Di Giacomo Daniela Lamy Aude Troncone Giancarlo Dal Mas Antonella Coletti Gino Frébourg Thierry Sabourin Jean Tosi Mario Ficorella Corrado Ricevuto Enrico |
| author_facet | Bruera Gemma Cannita Katia Di Giacomo Daniela Lamy Aude Troncone Giancarlo Dal Mas Antonella Coletti Gino Frébourg Thierry Sabourin Jean Tosi Mario Ficorella Corrado Ricevuto Enrico |
| author_sort | Bruera Gemma |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of metastatic colorectal cancer (MCRC), particularly integrated with secondary liver surgery in liver-limited (L-L) patients. The prognostic value of the <it>KRAS </it>genotype in L-L and other or multiple metastatic (O/MM) MCRC patients treated with the FIr-B/FOx regimen was retrospectively evaluated.</p> <p>Methods</p> <p>Tumoral and metastatic samples were screened for <it>KRAS </it>codon 12 and 13 and <it>BRAF </it>mutations by SNaPshot and/or direct sequencing. Fit MCRC patients <75 years were consecutively treated with FIr-B/FOx regimen: weekly 12-h timed flat-infusion/5-fluorouracil (TFI 5-FU) 900 mg/m<sup>2</sup>, days 1, 2, 8, 9, 15, 16, 22 and 23; irinotecan (CPT-11) 160 mg/m<sup>2 </sup>plus BEV 5 mg/kg, days 1, 15; oxaliplatin (OXP) 80 mg/m<sup>2</sup>, days 8, 22; every 4 weeks. MCRC patients were classified as L-L and O/MM. Activity and efficacy were evaluated and compared using log-rank test.</p> <p>Results</p> <p>In all, 59 patients were evaluated: 31 <it>KRAS </it>wild-type (53%), 28 <it>KRAS </it>mutant (47%). At 21.5 months median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were, respectively: <it>KRAS </it>wild-type 90%, 14 months, 38 months; <it>KRAS </it>mutant 67%, 11 months, 20 months. PFS and OS were not significantly different. PFS and OS were significantly different in L-L compared to O/MM evaluable patients. In <it>KRAS </it>wild-type patients, clinical outcome of 12 L-L compared to 18 O/MM was significantly different: PFS 21 versus 12 months and OS 47 versus 28 months, respectively. In <it>KRAS </it>mutant patients, the clinical outcome of 13 L-L compared to 14 O/MM was not significantly different: PFS 11 months equivalently and OS 39 versus 19 months, respectively.</p> <p>Conclusions</p> <p>The <it>KRAS </it>genotype wild-type and mutant does not significantly affect different clinical outcomes for MCRC patients treated with the first-line FIr-B/FOx intensive regimen. <it>KRAS </it>wild-type patients with L-L disease may achieve a significantly prolonged clinical outcome due to integration with secondary liver surgery, with respect to <it>KRAS </it>mutant patients.</p> |
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| publishDate | 2012-11-01 |
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| spelling | doaj.art-3f83e1c848914d01a3c6e3d30b3a7c192022-12-21T23:26:50ZengBMCBMC Medicine1741-70152012-11-0110113510.1186/1741-7015-10-135Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic diseaseBruera GemmaCannita KatiaDi Giacomo DanielaLamy AudeTroncone GiancarloDal Mas AntonellaColetti GinoFrébourg ThierrySabourin JeanTosi MarioFicorella CorradoRicevuto Enrico<p>Abstract</p> <p>Background</p> <p>Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of metastatic colorectal cancer (MCRC), particularly integrated with secondary liver surgery in liver-limited (L-L) patients. The prognostic value of the <it>KRAS </it>genotype in L-L and other or multiple metastatic (O/MM) MCRC patients treated with the FIr-B/FOx regimen was retrospectively evaluated.</p> <p>Methods</p> <p>Tumoral and metastatic samples were screened for <it>KRAS </it>codon 12 and 13 and <it>BRAF </it>mutations by SNaPshot and/or direct sequencing. Fit MCRC patients <75 years were consecutively treated with FIr-B/FOx regimen: weekly 12-h timed flat-infusion/5-fluorouracil (TFI 5-FU) 900 mg/m<sup>2</sup>, days 1, 2, 8, 9, 15, 16, 22 and 23; irinotecan (CPT-11) 160 mg/m<sup>2 </sup>plus BEV 5 mg/kg, days 1, 15; oxaliplatin (OXP) 80 mg/m<sup>2</sup>, days 8, 22; every 4 weeks. MCRC patients were classified as L-L and O/MM. Activity and efficacy were evaluated and compared using log-rank test.</p> <p>Results</p> <p>In all, 59 patients were evaluated: 31 <it>KRAS </it>wild-type (53%), 28 <it>KRAS </it>mutant (47%). At 21.5 months median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were, respectively: <it>KRAS </it>wild-type 90%, 14 months, 38 months; <it>KRAS </it>mutant 67%, 11 months, 20 months. PFS and OS were not significantly different. PFS and OS were significantly different in L-L compared to O/MM evaluable patients. In <it>KRAS </it>wild-type patients, clinical outcome of 12 L-L compared to 18 O/MM was significantly different: PFS 21 versus 12 months and OS 47 versus 28 months, respectively. In <it>KRAS </it>mutant patients, the clinical outcome of 13 L-L compared to 14 O/MM was not significantly different: PFS 11 months equivalently and OS 39 versus 19 months, respectively.</p> <p>Conclusions</p> <p>The <it>KRAS </it>genotype wild-type and mutant does not significantly affect different clinical outcomes for MCRC patients treated with the first-line FIr-B/FOx intensive regimen. <it>KRAS </it>wild-type patients with L-L disease may achieve a significantly prolonged clinical outcome due to integration with secondary liver surgery, with respect to <it>KRAS </it>mutant patients.</p>http://www.biomedcentral.com/1741-7015/10/135disease extensionintensive regimen<it>KRAS </it>mutationsmetastatic colorectal cancertriplet chemotherapy plus bevacizumab |
| spellingShingle | Bruera Gemma Cannita Katia Di Giacomo Daniela Lamy Aude Troncone Giancarlo Dal Mas Antonella Coletti Gino Frébourg Thierry Sabourin Jean Tosi Mario Ficorella Corrado Ricevuto Enrico Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease BMC Medicine disease extension intensive regimen <it>KRAS </it>mutations metastatic colorectal cancer triplet chemotherapy plus bevacizumab |
| title | Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease |
| title_full | Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease |
| title_fullStr | Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease |
| title_full_unstemmed | Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease |
| title_short | Prognostic value of <it>KRAS </it>genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease |
| title_sort | prognostic value of it kras it genotype in metastatic colorectal cancer mcrc patients treated with intensive triplet chemotherapy plus bevacizumab fir b fox according to extension of metastatic disease |
| topic | disease extension intensive regimen <it>KRAS </it>mutations metastatic colorectal cancer triplet chemotherapy plus bevacizumab |
| url | http://www.biomedcentral.com/1741-7015/10/135 |
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