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Phase II Study of Tosedostat With Cytarabine or Decitabine in Newly Diagnosed Older Patients With Acute Myeloid Leukaemia or High-Risk MDS

Phase II Study of Tosedostat With Cytarabine or Decitabine in Newly Diagnosed Older Patients With Acute Myeloid Leukaemia or High-Risk MDS

Raya Mawad, Pamela S Becker, Paul Hendrie, Bart Scott, Brent L Wood, Carol Dean, Vicky Sandhu, Hans Joachim Deeg, Roland Walter, Lixia Wang, Han Myint, Jack W Singer, Elihu Estey, John M Pagel

Br J Haematol. 2016 Jan;172(2):238-45.

PMID: 26568032

Abstract:

Tosedostat, an oral aminopeptidase inhibitor, has synergy with cytarabine and hypomethylating agents. We performed a Phase II trial to determine rates of complete remission (CR) and survival using tosedostat with cytarabine or decitabine in older patients with untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Thirty-four patients ≥60 years old (median age 70 years; range, 60-83) were randomized to receive tosedostat (120 mg on days 1-21 or 180 mg continuously) with 5 d of either cytarabine (1 g/m2 /d) or decitabine (20 mg/m2 /d) every 35 d. Twenty-nine patients (85%) had AML, including 15 (44%) with secondary AML/MDS, and 5 (15%) had MDS-refractory anaemia with excess blasts type 2. The CR/CR with incomplete count recovery (CRi) rate was 53% [9 in each arm; 14 CR (41%) and 4 CRi (12%)], attained in 6 of 14 patients with adverse cytogenetics and 4 of 7 with FLT3-internal tandem duplication mutations. Median follow-up was 11.2 months (range, 0.5-22.3), and median survival was 11.5 months (95% confidence interval, 5.2-16.7). Twenty-three patients (67.6%) were treated as outpatients and 10 of these patients required hospitalization for febrile neutropenia. No Grade 3-4 non-haematological toxicities required withdrawal from study. Tosedostat with cytarabine or decitabine is tolerated in older patients with untreated AML/MDS, results in a CR/CRi rate of >50%, and warrants further study in larger trials.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP238750771	Tosedostat		238750-77-1	Price

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