A phase 1b expansion study of TAS-102 with oxaliplatin for refractory metastatic colorectal cancer.

BACKGROUND: TAS-102, a novel antimetabolite, is approved for treatment of refractory metastatic colorectal cancer (CRC). This study sought to determine whether the addition of TAS-102 to oxaliplatin (TAS-OX) was safe and effective in metastatic CRC previously treated with oxaliplatin. METHODS: This investigator-initiated, open-label, single-arm phase 1b study enrolled patients with metastatic CRC previously treated with 5-fluorouracil, irinotecan, and oxaliplatin. In dose escalation, TAS-102 was given at 3 dose levels: 25, 30, and 35 mg/m2 twice daily on day 1 to day 5 with 85 mg/m2 oxaliplatin on day 1 in 14-day cycles. The primary endpoint of dose escalation was the recommended dose for expansion, and in dose expansion, the primary endpoint was overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). RESULTS: Forty-one patients were treated with TAS-OX. No dose-limiting toxicities were observed in the 11 patients treated in escalation. The recommended dose for expansion was 35 mg/m2 TAS-102 twice daily on day 1 to day 5 in combination with 85 mg/m2 oxaliplatin on day 1 in 14-day cycles. In the intention-to-treat population, the ORR was 2.4% (95% CI, 0%-12.9%) with 1 of 41 patients having a partial response, although 12 (29%) had tumor shrinkage. The median progression-free survival was 2.7 months (95% CI, 2.4-4.8 months) and median overall survival was 6.8 months (95% CI, 5.7-10 months). CONCLUSIONS: TAS-OX is safe with no unexpected toxicities at standard doses of each agent. The combination did not result in a clinically meaningful ORR, although progression-free survival and overall survival were encouraging in this heavily pretreated population. LAY SUMMARY: For metastatic colorectal cancer, the treatment combination of TAS-102 and oxaliplatin was found to be well-tolerated and revealed no unexpected side effects. Twelve of 41 patients had reductions in the size of their tumor, and the study treatment delayed the time to tumor growth as opposed to what would be expected.

Prevalence of Metabolic Syndrome in Hispanic and Non-Hispanic Patients With Schizophrenia.

BACKGROUND: Metabolic syndrome, a constellation of truncal obesity, dyslipidemia, disturbed insulin and glucose metabolism, and hypertension, is associated with the development of diabetes mellitus and coronary heart disease. However, the prevalence of metabolic syndrome in Hispanic patients with schizophrenia and whether they differ from comparable non-Hispanic patients is uncertain. METHOD: This cross-sectional study, conducted from January 2002 to May 2002, included 48 patients with schizophrenia who were recruited from an outpatient psychiatric clinic. Metabolic syndrome was defined using the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. RESULTS: The prevalence of metabolic syndrome was 63% in all patients with schizophrenia. The metabolic syndrome was present in 41% of non-Hispanic patients and in 74% of Hispanic patients with schizophrenia. Metabolic syndrome was present in 70% of Cuban Americans and 88% of other Hispanic subgroups with schizophrenia. Metabolic syndrome was associated with waist circumference (p <.05) and high-density lipoprotein cholesterol (p <.05) in logistic regression analysis. CONCLUSIONS: These data suggest that schizophrenic patients have a 3-fold greater risk to develop metabolic syndrome than the general population. Hispanic schizophrenic patients have a significantly greater prevalence of metabolic syndrome than non-Hispanic schizophrenic patients (p <.05). An increased waist circumference is the strongest clinical correlate with metabolic syndrome in schizophrenic patients.