Note: This abstract was presented at the 2012 ASCO annual meeting in June 2012. The full abstract may be reviewed on the ASCO Annual Meeting Web site. Use the abstract number to access the full report.
Abstract # 6520
Myelodysplastic syndrome (MDS) is a heterogeneous disease, with varied options for treatment. These range from supportive care, which includes blood product transfusions and the use of growth factors, to intensive therapy with allogeneic hematopoietic stem cell transplantation (HSCT). Treatment selection should be based on the patient’s age, performance status, and International Prognostic Scoring System (IPSS and IPSS-Revised) subgroup classification.
The main goal of MDS therapy is to provide symptom control and to improve quality of life for lower-risk subtypes, and to extend survival and delay transformation to AML in higher-risk groups. Treatment is indicated for higher-risk MDS under most circumstances regardless of blood counts or symptoms. The only curative option for MDS is allogeneic HSCT.
For patients with higher-risk MDS, the two drugs approved by the Food and Drug Administration are azacitidine (5-AZA, Vidaza®) and decitabine (Dacogen®). Both of these drugs are hypomethylating agents, which can help decrease the growth of abnormal bone marrow cells and restore gene expression. Failure of the hypomethylating agents, especially in the setting of patients who are not HSCT eligible, is a poor prognostic sign. Median survival is approximately 6 months in this cohort of patients.
In this abstract, sapacitabine is studied in the setting of hypomethylating agent failure. Sapacitabine is an oral nucleoside analogue, which essentially works by breaking the DNA and does not allow the cancer cell to divide. This is a multi-center, randomized Phase II study. In general, a Phase II study is a clinical trial whereby a drug is given to a patient with the intent of knowing whether the patient will respond to the therapy; this also provides information to the study investigators regarding the safety of the drug. Randomized means that the patients were randomly assigned to the various treatment groups. The patients were divided into 3 different dosing regimens of sapacitabine. This study enrolled a total of 63 patients, all of whom were 60 years of age or older, previously treated with hypomethylating agents, and had higher-risk MDS. Results indicated that the patients had an overall survival of 252 days, with a total of 10 patients who have responded (4 complete remission and 6 major hematological improvement). Additionally, 26 patients achieved stable disease lasting longer than 16 weeks. The 30-day all-cause mortality rate was 5 percent. Common side effects included: fatigue, nausea, diarrhea, constipation, swelling, and low blood counts (anemia, neutropenia, and thrombocytopenia).
In conclusion, the study showed that sapacitabine appears to be a safe and effective drug with all 3 dosing regimens. Further studies are needed to evaluate the long-term effects of sapacitabine.