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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.

630 Background: TAS-102 is an oral combination of the anti-metabolite 5-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI), preventing the degradation of FTD. It is approved as mCRC monotherapy with improved survival. Oxaliplatin is often reintroduced in mCRC after progressive disease (PD) on maintenance 5-FU although response is poor. The decreased efficacy may be related to acquired 5-FU resistance. We therefore explored the safety and efficacy of oxaliplatin in combination with an alternative and non cross-resistant anti-metabolite, TAS-102. Methods: Phase 1 of TAS-OX is a 3+3 dose-escalating study at a starting dose of TAS-102 25 mg/m2 and oxaliplatin 85 mg/m2 with three dose levels (table). TAS-102 is administered days 1-5 and oxaliplatin day 1, every 2 weeks. Eligible patients previously received 5FU, oxaliplatin, irinotecan, appropriate biologics, had measurable disease, usual laboratory parameters, and ECOG PS 0-1. The primary objective was to determine the recommended phase II dose (RP2D). Results: Twelve patients were evaluable for dose limiting toxicity (DLT). No DLTs were observed. Treatment related grade ≥ 3 AEs were neutropenia (n = 4) and thrombocytopenia (n = 1). No AEs resulted in treatment discontinuation. Two patients (dose levels 2 and 3) required dose reductions for prolonged neutropenia. Median number of cycles for all treated patients was 6 ± 4. The disease control rate (DCR) at 8 weeks was 67%. Best response in all evaluable patients was 1 PR (8%) 7 (59%) SD and 4 (33%) PD. Conclusions: The RP2D of TAS-102 is 35 mg/m2 in combination with oxaliplatin 85 mg/m2. No DLTs were observed and no unexpected AEs were seen. The DCR in this heavily pretreated patient population is encouraging. Phase II is now enrolling at this dose (NCT 02848079). Clinical trial information: NCT02848079. [Table: see text]

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.

15013 Background: The efficacy of gemcitabine in pancreatic cancer can be improved by its combination with erlotinib. Likewise, a fixed dose-rate infusion of gemcitabine seems to be superior to the conventional 30-minute infusion. Our objective was to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with erlotinib in patients with advanced adenocarcinoma of the pancreas. Methods: From May 2005 to October 2006, 21 chemotherapy-naïve patients were included, median age 62 years (range 47 - 78), male/female 12/9. Five patients (24%) had locally advanced disease and 16 (76%) distant metastases. The Karnofsky score was 80–100 in 11 (52%), and 60–70 in 10 (48%). Treatment consisted of gemcitabine 1200 mg/m2 given as a 120-minute infusion on days 1, 8, 15, plus erlotinib 100 mg p.o daily. Cycles were repeated every 4 weeks. Results: A total of 80 cycles of chemotherapy were delivered with a median of 3.8 per patient (range 1- 8). There were five partial responses (24%, 95% CI: 8.4 - 47.6%), whereas seven patients had stable disease (33%) and 9 had a progression (43%). The median time to progression was 4 months. After a median follow-up of 6 months (1–14 months), the median overall survival has not been achieved. Toxicity was low. Grade 3- 4 WHO toxicities per patient were as follows: neutropenia in 5 (24%), thrombocytopenia in 1 (5%) and anaemia in 3 (14%). Grade 1–2 rash appeared in 8 (38%) and grade 3 in 3 (14%). Four patients (19%) had diarrhoea grade 1–2. Conclusions: These preliminary results suggest that a fixed dose-rate infusion of gemcitabine associated with erlotinib is active and well tolerated in patients with advanced pancreatic carcinoma. No significant financial relationships to disclose.