The MDS Beacon™

The addition of valproic acid (Depakene) to Dacogen (decitabine) may not improve response rates compared to Dacogen alone in the treatment of myelodysplastic syndromes (MDS) due to valproic acid blocking how Dacogen works.

The findings are from a Phase 2 study conducted by researchers at the M.D. Anderson Cancer Center in Houston and were presented at the 51st annual American Society of Hematology (ASH) meeting and exposition held in New Orleans in December.

Valproic acid activates the production of protein based on a person’s genes by inhibiting an enzyme called histone deacetylase. Valproic acid is most commonly used to treat seizures, bipolar disorder, and migraine headaches, but recent studies have shown that it may be effective against a wide range of cancers. 

Previous studies have shown that valproic acid has the potential to suppress MDS and other blood- or bone-related cancers when given in combination with hypomethylating agents such as Dacogen and Vidaza (azacitidine), which regulate cell division (see related Beacon news). 

However, interim results from the M.D. Anderson Cancer Center study showed similar response and survival rates for patients receiving either Dacogen alone or Dacogen in combination with valproic acid. MDS patients in both treatment groups responded better (64 percent overall response, 39 percent complete response) than patients with acute myeloid leukemia (46 percent overall response, complete response 25 percent).

To better understand the results, the researchers further investigated the effect of the two different treatment regimens on certain genes involved in the development of MDS.

They found that the addition of valproic acid to Dacogen effectively increased the production of key proteins. However, researchers also discovered that valproic acid reduced Dacogen’s efficacy. These two opposing trends may be the reason why the response rates were similar with and without the addition of valproic acid to Dacogen.

The researchers suggested a stronger histone deacetylase inhibitor administered on different days than Dacogen may be necessary to improve the efficacy of Dacogen for the treatment of MDS. 

For more information, please see abstract 3808 on the 2009 ASH meeting Web site.