Final results of a Phase I study of Liposome Entrapped Paclitaxel (LEP-ETU) in patients with advanced cancer
2005; Lippincott Williams & Wilkins; Volume: 23; Issue: 16_suppl Linguagem: Inglês
10.1200/jco.2005.23.16_suppl.2048
ISSN1527-7755
AutoresNevena Damjanov, Mayer Fishman, J. L. Steinberg, Gerald J. Fetterly, A L Haas, Amy Grahn, C. Lauay, J. L. Dul, Jeffrey W. Sherman, Eric H. Rubin,
Tópico(s)Lung Cancer Research Studies
Resumo2048 Background: LEP-ETU is an easy-to-use liposomal formulation of paclitaxel developed to reduce toxicities while maintaining or enhancing efficacy by eliminating the drug formulation component polyoxyethylated castor oil (CremophorEL). Methods: This Phase I, dose-escalation study was designed to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of LEP-ETU in adult patients with advanced cancer. Paclitaxel pharmacokinetics (PK) and antitumor effects of LEP-ETU were also assessed. LEP-ETU was infused intravenously over 90 minutes once every 21 days. Results: A total of 25 patients received LEP-ETU at doses of 135 (n=3), 175 (n=4), 225 (n=3), 275 (n=3), 325 (n=6), and 375 (n=6) mg/m2. Primary tumor sites included breast, ovary, and colon. Initial patients (n=9, 135–225 mg/m2) were premedicated on the day of infusion to prevent infusion-related reactions (IRRs); later patients (n=16, 225–375 mg/m2) were not premedicated and 75% completed multiple infusions without IRRs. The remaining 25% were able to continue treatment with premedication. The most frequent adverse events were fatigue, nausea, anemia, hypoesthesia, and neutropenia. One DLT of neutropenia occurred at 325 mg/m2. Two patients experienced DLTs (1 neutropenia, 1 neuropathy) at 375 mg/m2. A dose of 325 mg/m2 was determined to be the MTD. Mean paclitaxel AUC0-∞ was linear at doses of LEP-ETU up to 325 mg/m2. Modeling data suggested that LEP-ETU may have a PK profile comparable to paclitaxel/Cremophor EL (Taxol) when both are administered at 175 mg/m2 over 180 minutes. Partial tumor response was observed in 3 patients (12%), stable disease in 11 patients (44%), and progressive disease in 7 patients (28%), with 4 patients (16%) not assessed (1 withdrawal, 3 DLTs in Cycle 1). Conclusions: Infusion of LEP-ETU over 90 minutes at doses above the MTD of Taxol was well tolerated. With or without premedication, most patients completed multiple infusions without experiencing IRRs. With increasing LEP-ETU doses, systemic exposure to paclitaxel was linear. Evidence of anti-tumor activity was observed, with partial response occurring in 3 patients and stable disease occurring in 11 patients. Next step studies have been initiated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NeoPharm
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