5--oleoyl-cytarabine and Neoplasms

Cytarabine (ara-C) has limited activity in solid tumours. CP-4055 (ELACYT) is a novel ara-C-5'-elaidic acid ester that may circumvent this limitation. CP-4055 maximum tolerated dose (MTD), pharmacokinetics and antitumor activity have been investigated in patients with solid tumours.. Thirty-four patients (19 malignant melanoma, 8 ovarian cancers and 7 NSCLC) received CP-4055 as a 30 min, or 2 hr intravenous (IV) infusion daily for 5 consecutive days every 3 or 4 weeks (D1-5 q3w or D1-5 q4w) in a dose escalation designed study with doses ranging from 30 to 240 mg/m(2)/day.. The most frequent CTC grade 1-2 adverse events (AEs) were nausea, fatigue, vomiting, anorexia and pyrexia. Most of the grade 3-4 AEs were neutropenia. The MTD was 200 mg/m(2)/day and 240 mg/m(2)/day for D1-5 q3w and D1-5 q4w, respectively. The MTD was independent of infusion time in the 4 week schedule. CP-4055 was maintained in plasma for up to 5-10 hr at dose levels >150 mg/m(2)/day. One objective partial response (PR) with time to progression (TTP) of 22 months was reported in an advanced malignant melanoma patient.. CP-4055 was well tolerated; the majority of the AEs were of CTC grade 1. The 3 week schedule was not recommended due to neutropenic nadir between days 18-26. The recommended dose was 200 mg/m(2)/day in a D1-5 q4w schedule. Efficacy data suggest that CP-4055 might be active in treatment of solid tumours.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Cytarabine; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Lung Neoplasms; Melanoma; Middle Aged; Neoplasms; Ovarian Neoplasms