| Autor: |
Jones, Suzanne, Hainsworth, John, Burris, Howard, Thompson, Dana, Raefsky, Eric, Johnson, Valerie, Calvert, Sharon, Bulanhagui, Cecile, Lebwohl, David, Greco, F. |
| Zdroj: |
Investigational New Drugs; Feb2002, Vol. 20 Issue 1, p55-61, 7p |
| Abstrakt: |
This phase I study wasconducted to determine the dose limitingtoxicity, maximum tolerated doses, andrecommended phase II doses of thecombination of JM-216 and paclitaxel. Patients received paclitaxel intravenouslyover one hour on day 1 of each cycle. OralJM-216 was administered on days 1–5starting after the paclitaxel infusion. Cycles were repeated every 21 days. Patients were accrued at nine differentdosing combinations. JM-216 doses rangedfrom 10–80 mg/m2/day and werecombined with paclitaxel doses of 150, 175,or 200 mg/m2. Forty-three patientswere treated with 146 cycles of therapy. Dose-limiting toxicity, consisting offebrile neutropenia and grade 3thrombocytopenia, was encountered in 2patients at the seventh dose level (JM-21680 mg/m2/day + paclitaxel175 mg/m2). Two intermediate doselevels were explored. The first level(JM-216 70 mg/m2/day + paclitaxel175 mg/m2) produced dose-limitingthrombocytopenia in 1 of 6 patients. However, two additional patients alsodemonstrated delayed recovery fromthrombocytopenia following treatment. As aresult, a second intermediate dose level(JM-216 60 mg/m2/day + paclitaxel200 mg/m2) was filled with sixpatients. No dose-limiting toxicities werereported in any patients at this doselevel. The combination of oral JM-216 andpaclitaxel is well-tolerated with minimalnon-hematologic and reversible hematologictoxicity. The recommended dose for phaseII study is JM-216 60 mg/m2/day for 5days and paclitaxel 200 mg/m2 on day 1repeated every 21 days. Higher doses ofJM-216 are associated with more severethrombocytopenia and delayed hematologicrecovery resulting in subsequent dosingdelays. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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