Combination Chemotherapy Shows Promise in Patients with Blood Cancers


Thioguanine and decitabine combination therapy show positive results in phase 1 trial.

Patients with relapsed and/or chemotherapy refractory blood cancers responded to a combination regimen of the chemotherapy drugs thioguanine and decitabine during a phase 1 clinical trial.

For the trial, investigators tested the efficacy of the combination therapy in 12 older patients with relapsed or chemotherapy refractory acute myeloid leukemia (AML) or chronic myelomonocytic leukemia. This included 6 patients whose disease had progressed after being previously treated with decitabine monotherapy.

There were 11 patients who completed the first treatment cycle, and 6 who completed a second cycle, with a median of 3 treatment rounds.

The results of the study, presented at the American Society of Hematology’s annual conference, showed that 8 of 11 patients responded to the combination therapy, including 6 who achieved a complete remission (5 in complete remission with incomplete count recovery).

Additional findings revealed that all patients who progressed after prior treatment with decitabine alone responded to the combination treatment, indicating the ability of the combination to overcome decitabine resistance.

Chemosensitivity assay results obtained before the start of treatment accurately predicted each patient’s response to the combination therapy. After treatment, 4 of the responders went on to receive a stem cell transplant.

“The goal of chemotherapy for patients with relapsed and/or refractory AML and other blood cancers is to achieve a remission that enables them to undergo a potentially curative stem cell transplant,” said investigator Dr Mark Frattini, MD, PhD. “With our phase 1 results, we have shown that this combination therapy can get some patients —–including those who failed to respond to or progressed after previous chemotherapy treatment with a single agent such as decitabine–– to that point. The next challenge for hematologic oncologists is to reduce morbidity and mortality associated with stem cell transplantation.”

After the completion of the study, 2 of the patients who had a stem cell transplant died from transplant-related toxicity, and another relapsed, according to the study. However, 1 patient remained in remission for more than 2 years.

“Outcomes are typically poor for older patients with advanced blood cancers, and new therapies are desperately needed to help patients with these cancers achieve remission,” Frattini said. “While our study was small, the response we saw in this phase 1, dose-escalating trial was encouraging.”

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