Oncology Medical News about myelodysplastic syndrome;glutathione analog prodrug

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Phase I-IIa multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra(R), TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome
Journal of Hematology & Oncology, 05/15/09

Raza A et al. - In a trial to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate of of ezatiostat hydrochloride liposomes for injection, it was shown that phase II studies of ezatiostat hydrochloride liposomes for injection in myelodysplastic syndrome (MDS) are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase II clinical development.

Methods

Phase I-IIa testing of ezatiostat for treatment of MDS was conducted in a multidose-escalation, multicenter study.
Phase I pts received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m2) intravenously (IV) on days 1-7 of a 14-day cycle until MDS progression or unacceptable toxicity.
In phase II, ezatiostat was administered on 2 dose schedules: 600 mg/m2 IV on days 1-5 or days 1-3 of a 21-day treatment cycle.

Results

54 pts with histologically confirmed MDS were enrolled.
Most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions.
Concentration of the primary active metabolites increased proportionate to ezatiostat dosage.
Trilineage responses were observed in 4 of 16 pts (25%) with trilineage cytopenia.
Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 pts (24%), HI-Neutrophil in 11 of 26 pts (42%), and HI-Platelet in 12 of 24 pts (50%).
These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements.
Improvement in bone marrow maturation and cellularity was also observed.

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