ABSTRACT
Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23-1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03-0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30-3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24-87%), 71% (95% CI 48-100%) and 88% (95% CI 74-100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069.
Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Immunologic Factors/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Adolescent , Adult , Aged , Drug Administration Schedule , Drug Dosage Calculations , Female , Humans , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/immunology , Purpura, Thrombocytopenic, Idiopathic/mortality , Purpura, Thrombocytopenic, Idiopathic/pathology , Recurrence , Rituximab , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. METHODS: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome. RESULTS: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.)
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Capecitabine , Cetuximab , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , ErbB Receptors/immunology , ErbB Receptors/metabolism , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Neoplasm Metastasis/drug therapy , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Quality of Life , Treatment Failure , ras Proteins/geneticsABSTRACT
A 43-year-old man presented with severe back pain. He had a history of morbid obesity, for which an esophagogastric silicone band was placed 2 years before presentation. Magnetic resonance imaging of the vertebral column showed multiple osseous metastases. On the computerized tomography scan of the abdomen, a tumor of the lower esophagus just proximal to the esophagogastric band was seen, of which histological examination revealed an esophageal adenocarcinoma. Esophageal adenocarcinoma after bariatric surgery has been described previously in only a few cases. Although there is no evidence for a causal relationship with bariatric surgery, one should bear in mind that the incidence of esophageal adenocarcinoma is increased in patients with morbid obesity because of the higher incidence of gastroesophageal reflux disease. Also, the symptoms of adenocarcinoma might be masked after bariatric surgery.
