PURPOSE: Preclinical studies have demonstrated significant @entity5 cell death when @entity136 is combined with radiation therapy. The optimal mode for concomitant delivery of drug and radiation therapy remains to be determined. A phase I/II study was undertaken to establish the maximum tolerated dose of infusional @entity136 when combined with radiation therapy in advanced @entity344 and to assess the response to treatment. MATERIALS AND METHODS: Twenty-five @entity1 with advanced or recurrent @entity344 were entered in this dose-escalation study. The initial dose of @entity136 was 50 mg/m2 as a 24-hour continuous intravenous infusion given weekly x 3 with concurrent radiation therapy. The @entity1 were given a week off chemotherapy after the third injection. The radiation therapy was continued during that week. @entity136 was thereafter resumed weekly for another 3 weeks or until the @entity1 completed the radiation therapy (whichever was earlier). Five @entity1 were treated at each dose level. The dose of the drug was escalated in increments of 50 mg/m2 if the @entity137 was acceptable at the previous level until the maximum tolerated dose was established. Thirteen @entity1 with advanced unresectable @entity14 and 12 @entity1 with advanced unresectable @entity5 were enrolled on the study. Radiation was delivered at 180 cGy/fraction to a total dose of 4000 cGy +/- boost. Because @entity137 was severe at the 150 mg/m2 dose level, three additional @entity1 were entered at this dose level. The dose was then dropped to 125 mg/m2, and five more @entity1 were entered at this dose level. Two additional @entity1 were then added in order to assess @entity137 . @entity1 follow-up ranged from 4 to 22 months, and the median was 8 months. RESULTS: All @entity1 were evaluable for @entity137 . The doses of 50 and 100 mg/m2 were well tolerated, but at 150 mg/m2, six of eight @entity1 experienced grade 3 or greater @entity137 . The dose was de-escalated to 125 mg/m2, and three of seven @entity1 showed grade 3 @entity294 and @entity353 . Clinical @entity5 response was evaluable in 20 @entity1 . Ten @entity1 had a complete clinical response (50%), five @entity1 had a partial response (25%), three @entity1 had no response, and two @entity1 had progression of disease. No @entity1 experienced late @entity137 related to either @entity136 administration or radiation therapy. Twelve @entity1 are currently alive. CONCLUSION: Based on these results, it appears that the maximum tolerated dose for weekly 24-hour infusion of @entity136 combined with radiation therapy is 100 mg/m2. @entity136 appears to be a potent radiation sensitizer, and when combined with radiation therapy, it has shown encouraging @entity5 responses. In this study, we found an overall response rate of 75% in @entity1 with locally advanced stage of disease. Further evaluation of @entity136 at 100 mg/m2 is being undertaken in preparation for a confirmatory multi-institutional phase II study.

Concurrent infusional @entity136 and radiation in the treatment of advanced unresectable XXXX : a phase I study.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient', 'Patient'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'toxicities'] @entity353 :: ('MESH:D015431', 'Disease') :: ['weight loss'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'pancreaticobiliary cancers', 'synergistic tumor'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity344 :: ('MESH:D005767', 'Disease') :: ['gastrointestinal malignancies', 'gastrointestinal malignancy'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['Gemcitabine', 'gemcitabine']
@entity5 :: (MESH:D009369,Disease) :: ['GI malignancy']
