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01-11-2011 | Clinical Trial Report

A phase I-II study of elacytarabine (CP-4055) in the treatment of patients with ovarian cancer resistant or refractory to platinum therapy

Authors: S. Pignata, F. Amant, G. Scambia, R. Sorio, E. Breda, W. Rasch, K. Hernes, C. Pisano, K. Leunen, D. Lorusso, L. Cannella, I. Vergote

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2011

Abstract

Purpose

Treatment of patients with recurrent ovarian cancer remains a challenge, and there is a need for new and more effective agents. A phase I-II study was designed to determine the recommended dose (RD) and the anti-tumour effect of a prolonged administration of elacytarabine, the elaidic ester of cytarabine, in patients with refractory/resistant recurrent ovarian cancer.

Experimental design

The primary objective of the dose escalation phase I part was to determine the RD for elacytarabine when given twice for five consecutive days in a 4-week schedule, D1-5 and D8(+2)-12(+2) q4w. Three to six patients were to be enrolled at each dose level. The start dose was elacytarabine 75 mg/m²/day. The phase II part was designed as a two-step study based on response.

Results

A total of 28 patients entered the study, 17 patients in the phase I part and 11^# patients in phase II. Three dose levels were tested: 75 mg/m²/day in 3 patients, 100 mg/m²/day in 7 + 11^# patients, and 125 mg/m²/day in 7 patients. Three (17.6%) patients in phase I experienced a dose limiting toxicity (DLT), all at the 125 mg/m²/day dose level, establishing the lower dose of 100 mg/m²/day as the RD. The DLTs were neutropenia grade 4 according to the Common Terminology Criteria for Adverse Events (CTCAE) and thrombocytopenia grade 4 (2 patients), and vomiting grade 2 with hospitalisation and hypokalaemia grade 3 (1 patient). The best response was a clinically meaningful stabilization observed in 3 patients. In two of them, the disease stabilization exceeded the previous platinum-free interval (PFI).

Conclusions

The RD for elacytarabine was 100 mg/m²/day, D1-5 and D8-12 q4w. The safety profile was comparable to the safety profiles reported in previous clinical studies with elacytarabine in solid tumours. Despite some longer-lasting disease stabilisations, two of them exceeding the previous progression-free interval, further investigations of elacytarabine in the ovarian cancer indication are not warranted.

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Title: A phase I-II study of elacytarabine (CP-4055) in the treatment of patients with ovarian cancer resistant or refractory to platinum therapy
Authors: S. Pignata
F. Amant
G. Scambia
R. Sorio
E. Breda
W. Rasch
K. Hernes
C. Pisano
K. Leunen
D. Lorusso
L. Cannella
I. Vergote
Publication date: 01-11-2011
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-011-1735-4

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Abstract

Purpose

Experimental design

Results

Conclusions

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