ORLANDO, Fla.—In older patients with myelodysplastic syndrome (MDS) refractory to hypomethylating agents, treatment with the orally administered nucleoside analogue sapacitabine resulted in 1-year survival rates of 29–35%, a randomized phase 2 study has found.
Sapacitabine, which has a unique ability to cause irreparable single-strand DNA breaks and induce G2 cell cycle arrest, was investigated in a multicenter study that randomized 60 patients to 3 dose regimens (20 in each arm) in older patients with MDS. Primary end point was 1-year survival. Secondary end points included rate of complete remission (CR), CR with incomplete platelet recovery (CRp), partial remission (PR), complete remission with incomplete blood count recovery (CRi), or hematological improvement (HI) and their corresponding treatment durations, Guillermo Garcia-Manero, MD, of MD Anderson Cancer Center, Houston, Texas, and colleagues reported.
The study used a selection design to identify the dose regimen that produced the better 1-year survival rate in the event that all 3 dose regimens were active. Eligibility included age ≥60 years with intermediate (int)-2 or higher-risk MDS previously treated with hypomethylating agents, ECOG 0-2, and adequate renal and hepatic functions.
Patients were randomized 1:1:1 to receive sapacitabine every 3 to 4 weeks as follows: Arm A, 200 mg bid x 7 days; Arm B, 300 mg bid x 7 days; and Arm C, 400 mg bid x 3 days/week x 2 weeks. The number of treatment cycles was not limited.
A total of 61 patients were treated. Median age was 73 years; 77% of patients were ≥70 years. Median follow-up was 237 days. Baseline bone marrow contained <5% blasts in 10 patients (16%); 5% to 10% blasts in 20 (33%); 11% to 20% blasts in 25 (41%); and 21% to 30% blasts in 6 (10%). Median number of cycles was 2; 34% of patients received ≥4 cycles.
At 1-year, 2 patients had a CR and 13, major HI. Response rates were Arm A, 24%; Arm B, 35%; and Arm C, 15%. Both CRs occurred in Arm A. Median time to response is 2 to 3 cycles (range, 1->15). Four deaths (7%) occurred within 30 days of randomization, 1 possibly related to sapacitabine. The number of survivors at 1-year was 29% for Arm A, 30% for Arm B, and 35% for Arm C. Commonly occurring adverse events (all grades, regardless of causality) included fatigue, nausea, diarrhea, constipation, abdominal pain, anorexia, peripheral edema, dyspnea, alopecia, pneumonia, arthralgia, febrile neutropenia, anemia, neutropenia, and thrombocytopenia, most of which were mild to moderate in intensity, the investigators concluded.