A phase I-II trial of @entity3003 and @entity1487 combination chemotherapy in advanced carcinoma of the XXXX .

@entity1 @entity135 @entity1665 @entity137 @entity3136 @entity390 @entity882 @entity66 @entity3003 @entity2347 @entity294 @entity391 @entity1295 @entity900 @entity1544 @entity1499 @entity1011 @entity3527 @entity3028 @entity1487
Twenty-nine @entity1 with recurrent or advanced, incurable @entity135 were entered into a phase I-II trial of @entity3003 in combination with @entity1487 ( @entity1487 ), 1,000 mg/m2/d continuous intravenous (IV) infusion for five days every 28 days. The initial dose of @entity3003 was 300 mg/m2 for @entity1 with Karnofsky performance scores greater than or equal to 70%, and 240 mg/m2 for @entity1 with scores of 50% to 60%. Subsequent doses were modified to achieve grade 2 myelo-suppression: WBC, 2,000 to 2,999 cells/microL; granulocytes, 1,000 to 1,499 cells/microL; and platelets, 50,000 to 75,000 cells/microL. Dose levels were 180, 240, 300, 360, and 420 mg/m2. Twenty-eight @entity1 had @entity1544 and one had an @entity2347 . There were 26 @entity1 with recurrent disease; 22 had received prior RT; only two had received other chemotherapy immediately before study entry. Three @entity1 had newly diagnosed incurable stage IV disease. The median performance status was 80% (range, 60% to 90%). All @entity1 had objectively measurable disease, and 28 were evaluable for response. There were three complete responses (CRs) and ten partial responses (PRs) (48% CR and PR); the median duration of response was 4.7 months (range, 1.5 to 15+ months). Dose-limiting @entity137 were @entity3028 , @entity882 , and @entity3136 . Prolonged myelosuppression delayed retreatment in eight @entity1 and delayed 19 of 107 (18%) courses. @entity3136 occurred in 61% and @entity294 in 29%. @entity1487 dosage was decreased in ten @entity1 (36%) for grade 2 or greater @entity3136 or @entity294 . Mild to moderate @entity390 and @entity391 occurred in 66% of @entity1 trials in which no pretreatment antiemetics were administered. Other @entity137 included @entity3527 from @entity1487 in 71%, @entity137 in 11%, mild @entity1665 in 25%, and @entity1295 in 54% of @entity1 . Nephrotoxicity ( @entity1011 greater than 2.0 mg/dL) occurred in one @entity1 . The dose of @entity3003 resulting in grade 2 @entity137 was 180 mg/m2 in one @entity1 , 240 mg/m2 in one, 300 mg/m2 in seven, 360 mg/m2 in ten, and 420 mg/m2 in one. Based on these results, we recommend a starting dose of @entity3003 , 300 mg/m2, in combination with five days of continuous infusion @entity1487 . In this dose and schedule, this combination was well tolerated and demonstrated antitumor activity in @entity135 . To confirm these promising results, a Southwest Oncology Group prospective randomized trial is in progress comparing @entity3003 and @entity1487 , @entity900 and @entity1487 , and standard-dose weekly @entity1499 in @entity66 @entity1 .
