4025 Background: BEV is an anti-VEGF-monoclonal antibody that improves survival in colorectal cancer. CPT/CIS is an active combination in the treatment of gastric and GEJ cancers with a median time to tumor progression(TTP) of 4.5 months. We performed this study to evaluate the efficacy and safety of the combination of CPT, CIS, and BEV in the treatment of gastric and GEJ cancers. Methods: Patients with previously untreated metastatic gastric and GEJ adenocarcinomas are eligible. The primary endpoint is to improve median TTP to 7.5 months. Response, survival, and safety are secondary endpoints. Evaluable or measurable disease was required. Patients received BEV 15mg/kg on day 1, CPT 65mg/m2 and CIS 30mg/m2 on days 1 and 8, every 21 days. Response is assessed by RECIST criteria, and CTCv 3.0 was used for toxicity assessment. Results: We have enrolled 24 patients with the following characteristics: median age 55(range 25–67), KPS 80%(70–90%), Male:Female 19:5. We have observed only 3 patients with progression at a median follow up of 3.4 months. The progression free survival at 3 months is 89%(95%CI: 81–100%), and at 6 months, is 76%(52–100%). Median TTP has not been reached. In 16 patients with measurable disease, we have observed 12 confirmed partial responses(75%, 95%CI:47–92%), 3 minor responses(15–29% reduction) and 1 stable disease. The combination therapy has been well tolerated, without an increase in CPT/CIS related toxicity: i.e. grade 3/4 neutropenia, nausea/vomiting, or diarrhea in 8% of patients. However, thromboembolic events were seen in 25% of patients(95%CI:11–45%): 4 patients with asymptomatic pulmonary embolism and 2 patients with deep vein thrombosis. Of 20 patients with their primary tumor in place, 2 patients had a gastric perforation, and another had a near perforation. There was no significant bleeding or toxicity related death. Conclusions: The combination of CPT/CIS/BEV appears active in gastric and GEJ cancers. Though preliminary, the high rates of response and disease control are noteworthy. The combination appears safe, although thromboembolic phenomenon are concerning. Accrual continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech

BACKGROUNDRetrospective reports suggest that therapeutic doses of acetaminophen may be associated with fulminant hepatic failure and death in alcoholic patients. Millions of patients use acetaminophen; the prevalence of alcoholism in the United States is 5% to 10%.OBJECTIVETo determine if hepatic injury was associated with maximal therapeutic dosing of acetaminophen to chronic alcohol abuse patients immediately following cessation of alcohol intake (the presumed time of maximal vulnerability).METHODSPatients entering an alcohol detoxification center were enrolled in a randomized, double-blind, placebo-controlled trial. Exclusion criteria were baseline values of aspartate or alanine aminotransferase greater than 120 U/L, international normalized ratio greater than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo was administered orally 4 times daily for 2 consecutive days and liver test results were monitored for 2 more days. Acetaminophen was not administered until the alcohol had been eliminated.RESULTSThere were 102 patients in the acetaminophen-treated group and 99 patients in the placebo-treated (control) group. Demographic data, alcohol history, and baseline blood test results were similar in both groups. The mean (SD) aspartate aminotransferase level on day 4 was 38.0 +/- 26.7 U/L in the acetaminophen-treated group and 37.5 +/- 27.6 U/L in the placebo-treated group. There were 4 patients in the acetaminophen-treated group and 5 in the placebo-treated group who developed an increase in their serum aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200 U/L in any patient. The mean (SD) international normalized ratio on day 4 was 0.96 +/- 0.09 in the acetaminophen-treated group and 0.98 +/- 0.11 in the placebo-treated group.CONCLUSIONRepeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.

PURPOSE:It has been observed previously in osteosarcoma (OS) that the degree of necrosis of the resected primary tumor following a period of preoperative chemotherapy is predictive of subsequent event-free survival (EFS). The aim of this study was to determine if more intensive preoperative chemotherapy would increase the proportion of patients with a good histologic response and improve EFS.PATIENTS AND METHODS:Seventy-three patients with OS were treated at Memorial-Sloan Kettering Cancer Center (MSKCC) on the T12 protocol between 1986 and 1993. Patients were randomized between therapy based on the T10 protocol and therapy with more intensive preoperative chemotherapy. The more intensive preoperative regimen consisted of two courses of cisplatin (CDDP) and doxorubicin (DOX) in addition to the usual preoperative regimen of high-dose methotrexate (HD MTX) and bleomycin, cyclophosphamide, and dactinomycin (BCD).RESULTS:The regimen with more intensive preoperative chemotherapy achieved a modest increase in the proportion of patients with a good histologic response (44% with a grade III or IV histologic response v 37% in the control arm, 33% with grade IV histologic response v 13% in the control arm). EFS continued to correlate with histologic response. The actuarial 5-year EFS in patients with localized disease was 78% for the regimen with more intensive preoperative chemotherapy and 73% for the control arm.CONCLUSION:Despite modest increases in the proportion of patients with good histologic response with intensified preoperative chemotherapy, no improvement in EFS was observed.

BACKGROUND Dose intensification of 5-fluorouracil (5-FU) is complicated by increased toxicity. 5-FU is a fluorine-substituted pyrimidine analog of uracil. In preclinical studies, administration of oral uridine (Ur) has been shown to allow for dose intensification of 5-FU with enhancement of its antitumor activity. Therefore, a Phase I trial was designed aimed at dose intensification of 5-FU as a component of a modified 5-FU-doxorubicin-methotrexate (FAMTX) regimen using oral Ur rescue. METHODS Methotrexate (MTX) was administered to all patients at a fixed dose of 1.5 g/m2. MTX was followed 24 hours later by escalating doses of 5-FU starting at 800 mg/m2 with leucovorin rescue. Cycles of 5-FU and MTX were repeated every 15 days. Every other cycle, patients received doxorubicin (“Adria cycles”) at a dose of 30 mg/m2. Oral Ur was administered at a dose of 8 gm/m2 every 6 hours for 12 doses. In the first phase of the study, patients received Ur only if they developed Grade 3 or 4 hematologic toxicity. In the second phase, all patients received Ur 24 hours after 5-FU on all cycles. RESULTS Without Ur rescue, the maximum tolerated dose (MTD) of 5-FU was 900 mg/m2 on the Adria cycles and 1.1 gm/m2 on the non-Adria cycles. With Ur, the MTD of 5-FU increased to 1.2 gm/m2 on the Adria cycles and to 1.6 gm/m2 on the non-Adria cycles. CONCLUSIONS In this modified FAMTX regimen, oral Ur administration allowed for dose-intensification of 5-FU, with a 33% increase in the MTD of 5-FU on the Adria cycles and a 45% increase in the MTD of 5-FU dose on the non-Adria cycles. Cancer 1997=6;78:1988-95.

Staff collected urine samples anonymously on 100 consecutive pregnant women in a women's clinic and simultaneously on 100 admissions to the “labor deck.” Urines were tested for cocaine, opiates, methadone, benzodiazepines, and THC. Nine percent of the urines were positive in the clinic setting, and 15% were positive on the labor deck; the incidence of cocaine‐ and opiate‐positive urines was significantly higher on the labor deck. The authors discuss the significance of these results. (American Journal on Addictions 1996; 5:351–353)

This study examines the mental health problems of a selected case sample of homeless mentally ill (HMI) men and women in Colorado. The HMI sample was selected to compare those HMI who utilize mental health services (N = 46) with those who do not (N = 50) with respect to psychopathology and to characteristics related to being ''difficult to treat.'' Findings show that although the HMI current users are slightly more dysfunctional than the non-users, the rates of serious disorders are high among both HMI groups. HMI current users of mental health services, particularly voluntary users, were found to have fewer ''difficult to treat'' characteristics than the nonusers.