Intravenous administration of CP-4055 (ELACYT (TM)) in patients with solid tumours. A phase I study

Dueland, Svein; Aamdal, Steinar; Lind, Michael J.; Thomas, Hilary; Sandvold, Marit Liland; Gaullier, Jean-Michel; Rasch, Wenche

Abstract

Purpose. Cytarabine (ara-C) has limited activity in solid tumours. CP-4055 (ELACYTT) 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. Material and methods. 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/m2/day. Results. 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/m2/day and 240 mg/m2/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/m2/day. One objective partial response (PR) with time to progression (TTP) of 22 months was reported in an advanced malignant melanoma patient. Conclusion. 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/m2/day in a D1-5 q4w schedule. Efficacy data suggest that CP-4055 might be active in treatment of solid tumours.

Citation

Dueland, S., Aamdal, S., Lind, M. J., Thomas, H., Sandvold, M. L., Gaullier, J.-M., & Rasch, W. (2009). Intravenous administration of CP-4055 (ELACYT (TM)) in patients with solid tumours. A phase I study. Acta Oncologica, 48(1), 137-145. https://doi.org/10.1080/02841860802183620

• Journal Article Type: Article
• Acceptance Date: Jan 1, 2009
• Online Publication Date: Jul 8, 2009
• Publication Date: Jan 1, 2009
• Journal: Acta Oncologica
• Print ISSN: 0284-186X
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 48
• Issue: 1
• Pages: 137-145
• DOI: https://doi.org/10.1080/02841860802183620
• Keywords: Oncology; Radiology Nuclear Medicine and imaging; Hematology; General Medicine
• Public URL: https://hull-repository.worktribe.com/output/409649
• Publisher URL: http://www.ingentaconnect.com/content/apl/sonc/2009/00000048/00000001/art00018