Phase I study of eribulin mesylate administered once every 21 days in patients with advanced solid tumors
Tan AR et al. - In a trial to evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of eribulin mesylate (E7389) administered every 21 days in pts with advanced solid tumors, it was shown that eribulin mesylate has a manageable toxicity profile at 2 mg/m2, with further dose escalation limited by neutropenia. Methods- Eribulin mesylate was given as a 1-hr infusion every 21 days at doses of 0.25, 0.5, 1, 2, 2.8, and 4 mg/m2.
- The MTD was identified using an accelerated titration design.
- The pharmacokinetics of eribulin were evaluated in the plasma and urine with the first dose.
Results- 21 pts were enrolled.
- At 4 mg/m2, 3 pts experienced a DLT of febrile neutropenia on day 7.
- Dose level was reduced to 2.8 mg/m2 where 2 of 3 pts experienced dose-limiting febrile neutropenia.
- 6 additional pts were enrolled at 2 mg/m2 (7 pts received this dose) and 1 of these pts experienced a neutropenic DLT.
- MTD of eribulin mesylate was 2 mg/m2.
- Nonhematologic toxicities included alopecia, fatigue, anorexia, and nausea.
- Pharmacokinetic analysis showed linear kinetics for eribulin over the dose range studied and a terminal half-life of 2 days.
- Plasma-concentration-time profile exhibited a rapid distribution phase followed by a slow elimination phase.
- Drug clearance was nonrenal.
- 1 pt with non–small cell lung cancer achieved an unconfirmed partial response and 12 pts had stable disease.
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