The Clinical Efficacy Of FOLFOX4Combined With Bevacizumab Or Cetuximab In The First Line Treatment Of Metastatic Colorectal Cancer

Objective: To observe the efficacy and main side effect of the bevacizumab orcetuximab combined FOLFOX4regimen as the first-line treatment in metastaticcolorectal cancer (mCRC). And analysis the correlation between efficacy and the KRASstatus.Methods: Forty-four mCRC patients,23male and21female; age28-85years,mean age63.1years; KRAS genetic testing:mutations in11cases, wild-type in33cases;colon adenocarcinoma is18cases, rectal adenocarcinoma is26cases. In to the group ofdata cut-off time in December2011. Bev group of19patients, KRAS mutations in11cases, eight cases of KRAS wild-type, receive bevacizumab infliximab (Bevacizumab,Bev) combined with FOLFOX4regimen. Bev dose to7.5mg/kg, q21d,, usesynchronization with chemotherapy. All patients accepted FOLFOX4chemotherapy(oxaliplatin130mg/m2on day1, plus leucovorin200mg/m2and fluorouracil as a400mg/m2bolus followed by600mg/m2infusion during22hours on days1and2), thenumber of chemotherapy cycle was2-6, and the median was four cycles.C225group25patients were KRAS wild-type, receive cetuximab (Cetuximab, C225) combined withFOLFOX4regimen, and cetuximab400mg/m2initial does followed by250mg/m2/week thereafter. C225frequency of use of2-16, with a median of8.7times. TheFOLFOX4regimen dose, usage with Bev groups, the number of chemotherapy cycles3-6, the median of4.56cycles. The patients of group A and group B every3weeks as acycle, evaluation ORR (objective response rate), DCR (disease control rate), PFS(progression free survival), OS (over survival), and treatment-related adverse reactions.Survival time using the Kaplan-Meier method, the applications log-rank method test thedifference in survival, prognostic factors was analyzed by multivariate Cox regressionanalysis. All the date using SPSS19.0software. Result: First,44patients overall ORR was45.45%, DCR was72.73%, PFS was8.0months, OS was22.0months. The group Bev ORR was47.37%, DCR was78.95%,PFS was8.9months, OS was23.1months; the group C225ORR was44%, DCR was68%, PFS was8.0months, OS was19.8months. Two groups were ORR, DCR, PFS,OS comparison (P>0.05), no statistically significant difference. Second, according toKRAS gene status subgroup analysis, KRAS mutant-type patients ORR was63.64%,DCR was81.82%, PFS was11.1months, OS was27.1months; KRAS wild-typepatients ORR was36.36%, DCR was66.67%, PFS was7.8months, OS was19.5months. Two groups ORR, OS comparison (P>0.05), no statistically significantdifference; DCR difference was statistically significant (P<0.01), PFS difference wassignificant (P<0.05). KRAS wild-type patients was divided into two groups according tothe different treatment options:Bev+FOLFOX4group ORR was12.5%,DCR was62.5%,PFS was7.0months, OS was17.9months;C225+FOLFOX4group ORR was44.00%, DCR was68.00%,PFS was8.0months, OS was19.5months. Two groupswere ORR, DCR, PFS, OS comparison (P>0.05), no statistically significant difference.The group Bev was divided into two groups according to KRAS gene status: KRASmutant-type patients ORR was63.64%，DCR was81.82%, PFS was11.8months, OSwas27.1months; KRAS wild-type patients ORR was12.5%, DCR was62.5%, PFS was7.0months, OS was17.9months. Two groups comparison ORR was significantdifference (P<0.05), DCR difference was no significant (P>0.05), PFS and OSdifference was statistically significant (P<0.01).KRAS mutations (11/44) of patientswith KRAS wild-type patients (33/44), RR (risk) of1.477, P=0.003,95%CI(0.657-3.319). Age≥70years (9/44) of patients with <70-year-old patients (35/44),RR1.077, P value of0.026,95%CI (0.442-2.622). Male patients (23/44) and femalepatients (21/44), RR0.704, P=0.047,95%CI (0.272-1.824).Third, adverse reactions:gastrointestinal reactions are manifested as I-II°nausea, vomiting, diarrhea, FOLFOX4+bevacizumab group and incidence of FOLFOX4+cetuximab treatment group were(57.89%,56%),(5.26%,24%); followed by I-II°bone marrow suppression, theincidence (47.37%,36%), respectively. The cetuximab therapy group two cases IV°myelosuppression out of group. Last, Multivariate Cox regression analysis: age, sex,KRAS gene status is an independent prognostic factors of metastatic colorectal cancer.Conclusion: First, bevacizumab or cetuximab Combined with FOLFOX4regimencan improve the first-line metastatic colorectal cancer patients ORR and DCR prolongPFS and OS. Second, Bevacizumab plus FOLFOX4regimen mutant KRAS mCRC patients may achieve better efficacy. Third, Bevacizumab or cetuximab combined withFOLFOX4regimen related to a lower incidence of adverse. Last, age, KRAS genestatus gender mCRC patient’s independent prognostic risk factors meaningful.