Showing papers by "Malcolm J. Moore published in 2004"

Phase II Study of Activated Charcoal to Prevent Irinotecan-Induced Diarrhea

Abstract: Purpose The dose-limiting toxicity of irinotecan (CPT-11; Camptosar) is delayed-onset diarrhea, with an incidence at the grade 3 to 4 level of 20% to 35%. SN38, its active moiety, is responsible by a direct effect on mucosal topoisomerase-I. The aim of this study was to assess whether activated charcoal (AC), possibly by adsorbing free lumenal SN38, can reduce irinotecan-induced diarrhea (CID) and optimize its dose-intensity. Patients and Methods Patients with advanced colorectal cancer receiving irinotecan 125 mg/m2 intravenously once a week for 4 weeks every 6 weeks were studied. In cycle 1, patients received irinotecan plus AC (5 mL aqueous Charcodote [1,000 mg AC] plus 25 mL water) given the evening before the irinotecan dose and then tid for 48 hours after the dose. In cycle 2, no AC was given. National Cancer Institute Common Toxicity Criteria diarrhea grade, irinotecan dose-intensity, and loperamide consumption were recorded prospectively in both cycles. Results Twenty-eight patients had completed ...

Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days.

Abstract: Fostriecin (CI-920) is a potent inhibitor of protein phosphatase 2A (PP2A) and protein phosphatase 4(PP4) found to have anticancer activity in preclinical testing. A phase I study was conducted to evaluate the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of this drug. Forty-six patients were treated with escalating doses of fostriecin (2–47 mg/m2) administered as a daily bolus infusion for five consecutive days. PK studies were performed at different time points following administration of fostriecin. Dose-limiting toxicities included: elevation of creatinine, bilirubin, and hepatic transaminases; nausea, anorexia, lethargy, and hypotension. PK studies were compatible with a two-compartment model. Regression analysis revealed a significant relationship between dose and clearance; however, the r2 value was only 0.168 indicating a low predictive value for the model. No significant difference was seen in PK parameters with repeated dosing during the same cycle. Although no tumor responses were seen, 16 patients had stable disease with a median duration response of 2.6 months. The study was closed before reaching MTD due to problems with the supply of fostriecin from the National Cancer Institute of the United States (NCI US). New methods for synthesizing fostriecin have recently been described and therefore further development of this unique anticancer agent may be warranted.

A phase I/II trial of BAY 43–9006 and gemcitabine in advanced solid tumors and in advanced pancreatic cancer

Abstract: 3059 Background: With its potent inhibitory effects against Raf-1 kinase and VEGFR-2, BAY 43–9006 (BAY) is a novel oral anticancer agent targeting signal transduction and angiogenic pathways. This study is designed to combine BAY and gemcitabine (GEM) due to their compatibility in preclinical models and non-overlapping clinical toxicities. Methods: An initial dose-escalating phase enrolled patients (pts) with advanced solid tumors, followed by an extended phase at the recommended dose (RD) for pts with advanced unresectable or metastatic pancreatic cancer. BAY is administered continuously while GEM is given at 1000 mg/m2 weekly x 7 followed by 1 rest week, then weekly x 3 every 4 weeks. Results: Forty-two pts have been enrolled with the following demographics: M:F ratio = 26:16; median age = 61 (range 39–83); ECOG 0:1:2:missing ratio = 17:19:5:1. Nineteen of the 42 pts were enrolled in the dose-escalating phase, the majority had ovarian (6 pts) or colorectal (5 pts) primaries, and 16/19 pts have had prior...

Outcome and toxicity of postoperative short course adjuvant radiation and chemotherapy following resection of adenocarcinoma of the rectum.

Abstract: A retrospective review has been performed to assess the outcome and toxicity of post-operative adjuvant therapy of 25 Gy/5 fractions/1 week following resection of stage II and III rectal cancer. Forty patients were treated between August 1992 and May 1995. The ages ranged from 42 to 79 (median 63); 32 were male (80%). At last follow up 32 were alive with 0.9 to 11.3 years of follow-up (median 6.6 years). The 5-year actuarial survival was 76% (95% CI: 62-91%). The local relapse free rate was 73% (95% CI: 58-88). Seven patients experienced grade 3 or 4 early toxicity. Three patients had grade 2 or 3 late toxicity. Although treatment was well tolerated, the local relapse rate observed was high. In view of the changes in surgical and pathological techniques in the last decade, further studies are required to determine the merits or otherwise of postoperative Short Course Adjuvant Radiation.