Regulation of epidermal growth factor receptor (EGFR) signaling pathways may play a relevant rolein determining the activity of cetuximab therapy in patients with metastatic colorectal cancer(MCRC). We investigated possible associations between genetic variants and clinical outcomes ofMCRC patients treated with cetuximab-irinotecan salvage therapy.Patients and MethodsPatients who underwent cetuximab-irinotecan salvage therapy after disease progression during orafter first-line bolus/infusional fluorouracil, leucovorin, and oxaliplatin chemotherapy and a secondlineirinotecan-based regimen were considered eligible for analysis of polymorphisms withputative influence on cetuximab-related pathways. Epidermal growth factor (EGF) 61AG, EGFreceptor (EGFR) 216GT, EGFR 497GA, EGFR intron-1 (CA)n dinucleotide short (S)/long (L)variant, cyclin-D1 870AG, immunoglobulin-G fragment-C receptors RIIIa 158GT, and RIIa131GA were studied for a possible association with overall survival (OS) as the primary endpoint. Additional analyses were addressed at possible associations among polymorphisms andEGFR expression, toxicity, and response.ResultsIn 110 assessable patients, significant association with favorable OS was observed for EGFRintron-1 S/S and EGF 61 G/G genotypes. In the multivariate model, EGFR intron-1 S/S and EGF 61G/G genotypes showed a hazard ratio of 0.41 (95% CI, 0.21 to 0.78; P .006) and 0.44 (95% CI,0.23 to 0.84; P .01), respectively. EGFR intron-1 S/S carriers showed more frequent G2-G3 skintoxicity (2 test 12.7; P .001) and treatment response (2 test 9.45; P .008) than EGFRintron-1 L/L carriers.ConclusionAlthough additional studies are required for confirmation, our findings could optimize the use ofcetuximab in MCRC patients.
Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer
SANTINI D;TONINI G;
2008-01-01
Abstract
Regulation of epidermal growth factor receptor (EGFR) signaling pathways may play a relevant rolein determining the activity of cetuximab therapy in patients with metastatic colorectal cancer(MCRC). We investigated possible associations between genetic variants and clinical outcomes ofMCRC patients treated with cetuximab-irinotecan salvage therapy.Patients and MethodsPatients who underwent cetuximab-irinotecan salvage therapy after disease progression during orafter first-line bolus/infusional fluorouracil, leucovorin, and oxaliplatin chemotherapy and a secondlineirinotecan-based regimen were considered eligible for analysis of polymorphisms withputative influence on cetuximab-related pathways. Epidermal growth factor (EGF) 61AG, EGFreceptor (EGFR) 216GT, EGFR 497GA, EGFR intron-1 (CA)n dinucleotide short (S)/long (L)variant, cyclin-D1 870AG, immunoglobulin-G fragment-C receptors RIIIa 158GT, and RIIa131GA were studied for a possible association with overall survival (OS) as the primary endpoint. Additional analyses were addressed at possible associations among polymorphisms andEGFR expression, toxicity, and response.ResultsIn 110 assessable patients, significant association with favorable OS was observed for EGFRintron-1 S/S and EGF 61 G/G genotypes. In the multivariate model, EGFR intron-1 S/S and EGF 61G/G genotypes showed a hazard ratio of 0.41 (95% CI, 0.21 to 0.78; P .006) and 0.44 (95% CI,0.23 to 0.84; P .01), respectively. EGFR intron-1 S/S carriers showed more frequent G2-G3 skintoxicity (2 test 12.7; P .001) and treatment response (2 test 9.45; P .008) than EGFRintron-1 L/L carriers.ConclusionAlthough additional studies are required for confirmation, our findings could optimize the use ofcetuximab in MCRC patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
