ABSTRACT
BACKGROUND: Perioperative chemotherapy improves outcome in resectable colorectal liver-only metastasis (CLM). This study aimed to evaluate perioperative CAPOX (capecitabine-oxaliplatin) plus bevacizumab in patients with poor-risk CLM not selected for upfront resection. PATIENTS AND METHODS: Poor-risk CLM was defined as follows: more than four metastases, diameter >5 cm, R0 resection unlikely, inadequate viable liver function if undergoing upfront resection, inability to retain liver vascular supply, or synchronous colorectal primary presentation. Patients underwent baseline computed tomography, magnetic resonance imaging, and/or positron emission tomography (PET) for staging and received neoadjuvant CAPOX plus bevacizumab, with resectability assessed every four cycles. Primary end point was radiological objective response rate (ORR). RESULTS: Forty-six patients were recruited, of which 91% underwent PET to ensure metastases confined to liver. Following neoadjuvant CAPOX plus bevacizumab, the ORR was 78% (95% confidence interval 63% to 89%). This allowed 12 of 30 (40%) patients with initial nonsynchronous unresectable CLM to be converted to resectability. In addition, 10 of 15 (67%) patients with synchronous resectable CLM underwent liver resection, with four additional patients being observed alone due to excellent response to neoadjuvant therapy. No grade 3-4 perioperative complications were seen. CONCLUSION: Neoadjuvant CAPOX plus bevacizumab resulted in a high response rate for patients with CLMs with poor-risk features not selected for upfront resection and converted 40% of patients to resectability.
Subject(s)
Adenocarcinoma/secondary , Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Capecitabine , Chemotherapy, Adjuvant , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Perioperative Care/methods , Risk FactorsABSTRACT
BACKGROUND: Carcinoembryonic antigen (CEA) flare may have a favourable response to chemotherapy, but its impact on survival is unknown. This study aimed to evaluate the incidence of CEA flare and its impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Patients with histologically proven advanced colorectal cancer undergoing first-line chemotherapy with three or more serial CEA measurements (one at baseline and two or more during treatment) were included. Patients were grouped according to CEA kinetic as flare (F), decreasing CEA, normal baseline CEA, stable CEA and increasing CEA (I). RESULTS: From January 2000 to February 2008, 837 patients were screened of whom 670 were eligible. CEA flare occurred in 78 (11.6%) patients. On multivariate analysis, compared with patients with increasing CEA, patients with CEA flare had a significantly better ORR [I versus F: 11% versus 73%; risk ratio (RR): 27.96; 95% confidence interval (CI): 9.55-81.88; P < 0.001], PFS (median 3.1 versus 8.3 months; RR: 0.38; 95% CI: 0.26-0.56; P < 0.001) and OS (median 10.9 versus 17.7 months; RR: 0.53; 95% CI: 0.34-0.82; P < 0.001). CONCLUSIONS: Compared with patients with rising CEA, flare was an independent favourable predictive and prognostic factor for tumour response and survival.
Subject(s)
Adenocarcinoma/blood , Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoembryonic Antigen/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/drug therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Irinotecan , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Survival Rate , Young AdultABSTRACT
The prognosis of patients with colorectal cancer (CRC) is affected by various factors at the time of diagnosis, including location of the tumor, gender, age and overall performance status of the patient. Predicting response and limiting drug-induced toxicity for patients with CRC are also critical. Interpatient differences in tumor response and drug toxicity are common during chemotherapy. Genomic variability of key metabolic enzyme complexes, drug targets and drug transport molecules are important contributing factors. At present, there is inconsistent and rather low use of pharmacogenetic testing in the clinical setting because of a lack of robust evidence or of resources. Patients' selection and tailored treatments by the introduction of genetic testing will hopefully allow better response prediction and limit drug-induced toxicity leading to improved patient outcomes in the most cost-effective way. Here, we review the main genetic alterations observed in familial and sporadic CRC and their associations with the metabolism, efficacy and toxicities of drugs used in this disease.
