Therapies for acute myeloid leukemia: vosaroxin

Figures & data

Table 1 Clinical studies using vosaroxin

Study	Patient no/disease	Treatment	Toxicity	Outcome
Phase Ib^Citation15	73 Re/Re	A: V weekly ×3 B: V twice weekly ×2	Neutropenic fever Stomatitis GI	MTD group A: 90 mg/m^2 MTD group B: 40 mg/m^2 CR/CRp 7%
Phase II^Citation16 (REVEAL-1)	113 Untreated	A: V 72 mg/m^2 weekly ×2 B: V 73 mg/m^2 weekly ×3 C: V 72 mg/m^2, d 1, 4 D: V 90 mg/m^2, d 1, 4	Neutropenic fever Stomatitis GI (nausea, diarrhea)	CR/CRp 32% MOS of responders 15.5 mo 30-/60-day all-cause mortality 12/31%
Phase Ib/II^Citation17 (combination)	108 Re/Re	A: V 10–90 mg/m^2, d 1, 4 + Cy 400 mg/m^2/d CIV, d 1–5 B: V 10–90 mg/m^2, d 1, 4 + Cy 1 g/m^2/d, d 1–5	Stomatitis Nausea Diarrhea	MTD group A: 80 mg/m^2 MTD group B: not achieved CR/CRp 26% MOS 6.9 mo 30-/60-day all-cause mortality 2.5/9%
Randomized^Citation20	104 Untreated	V 72 mg/m^2, d 1, 4 vs LDAC 20 mg BID, d 1–10	GI (stomatitis/diarrhea) significantly worse in the V arm	CR/CRp V vs LDAC 26% vs 30%; P=0.7 12-mo survival V vs LDAC 12% vs 31%; P=0.003
Randomized^Citation20	104 Untreated	V 72 mg/m^2, d 1, 4+ LDAC 20 mg BID, d 1–10 vs LDAC 20 mg BID, d 1–10	GI (stomatitis/diarrhea) significantly worse in the V + LDAC arm	CR/CRp V + LDAC vs LDAC 38% vs 34%; P=0.6 12-mo survival V + LDAC vs LDAC 33% vs 37%; P=0.3
Phase III^Citation18 Double-blind, randomized (VALOR)	705 Re/Re	V 90 mg/m^2, d 1, 4 + Cy 1 g/m^2/d; d 1–5 vs placebo + Cy 1 g/m^2/d; d 1–5	Neutropenic fever, infection, GI: V + Cy 33% Placebo + Cy 17%	CR/CRp V + Cy vs placebo + Cy 38% vs 19% MOS V + Cy vs placebo + Cy  All patients:  7.5 vs 6.1 mo; P=0.06  Censored for allotransplant:  6.7 vs 5.3 mo; P=0.027  Patients aged 60 years and older:  7.1 vs 5.0 mo; P=0.003  Early relapsed patients:  6.7 vs 5.2 mo; P=0.039 30-day all-cause mortality V + Cy vs placebo + Cy 8% vs 7% 60-day all-cause mortality V + Cy vs placebo + Cy 20% vs 19%

Abbreviations: BID, twice daily; CIV, continues intravenous infusion; CR, complete remission; CRp, CR with incomplete platelet recovery; Cy, cytarabine; d, day; GI, gastrointestinal; LDAC, low-dose Ara-C; mo, months; MOS, median overall survival; MTD, maximum tolerated dose; Re/Re, relapsed/refractory; V, vosaroxin.

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