| Objective:To evaluate the efficacy and toxicities of cetuximab in metastatic colorectal cancer and analyze the associations between clinical factors and response to cetuximab.Methods:A total of27patients with metastatic colorectal cancer treated with cetuximab at the department of medical oncology in Peking Union Medical College Hospital from December2004to September2010were included. Clinical characteristics, tumor KRAS mutation status, treatment regimens, response rate, progression-free survival and overall survival were analyzed retrospectively. The response to treatment was evaluated according to the RECIST1.0criteria, and toxicities were evaluated using CTCAE v3.0(common terminology criteria for adverse events version3.0). Subgroup analyses were performed to investigate the impact of the concurrent chemotherapy regimen, duration of cetuximab treatment, history of adjuvant chemotherapy, number of involved organs, extra-liver or liver metastases, grade of skin reactions, primary tumor site, and age on the tumor response. Statistical analyses were carried out using Kaplan-Meier method, log-rank test and Cox proportional hazard regression model.Results:Tumor KRAS mutation was screened in26patients of the enrolled27patients, all of the26patients had wild-type KRAS. Efficacy can be evaluated in25patients including22patients (21patients had wild-type KRAS) receiving cetuximab in first-line therapy,2in second-line therapy and1in third-line therapy. Patients with evaluable response had a median duration of6cycles (ranging from1to12) of chemotherapy treatment,8(ranging from3to27) weeks of cetuximab treatment. Among the22patients receiving cetuximab in their first-line therapy,1patient achieved CR,4patients achieved PR,15patients had stable disease, and2patients experienced disease progression. The response rate was22.7%, and disease control rate was90.8%, with the median progression free survival and median overall survival of6.0months (95%confidence interval0.0-12.0) and21.0months (95%confidence interval10.3-31.7), respectively. For the2patients receiving cetuximab in their second-line therapy,1patient had SD, and the other one had PD, with PFS of11months and1month, OS of18months and9months, respectively. Patient who had cetuximab in the third-line therapy had PD, PFS was1.5months, and OS was3.5months. Univariate and multivariate analyses of the associations between clinical features and response of the patients receiving cetuximab in their first-line therapy showed that PFS and OS of patients having>12weeks of cetuximab treatment were significantly longer compared with patients having<12weeks of cetuximab treatment. Patients with single organ involvement, or liver-confined metastasis, or grade3to4skin reactions have improved PFS, OS or RR compared with those with multiple organ involvement, or extra-liver metastasis or grade1to2skin reactions, respectively, but the difference were not statistically significant. The association between chemotherapy regimen (i. e. oxaliplatin-based or irinotecan-based) and survival, with regard to PFS or OS, was not significant, nor was there a significant interaction of primary tumor site, age, or history of adjuvant chemotherapy with tumor response. Toxicities could be evaluated in27patients. The most common toxicities were skin reactions (77.8%), diarrhea (25.9%), neurotoxicities and myelosuppression. Most of the toxicities could be tolerated, and related to the chemotherapy.Conclusions:Cetuximab combined with chemotherapy is effective for KRAS wild-type metastatic colorectal cancer. Toxicities could be tolerated. There was a significant interaction between the duration of cetuximab treatment with the tumor response. Patients with single organ involvement, or grade3to4skin reactions, or metastases confined to liver were associated with a trend toward improved survival. |
PDF Full Text Request