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URL http://www.rockymountainbmt.com/news/Leukemia-treated-with-bortezomib-experienced-enhanced-cytotoxic-effects-of-combination-chemotherapy-1108.html

Leukemia treated with bortezomib experienced enhanced cytotoxic effects of combination chemotherapy

06-29-2006

Bortezomib could be used to potentiate the cytotoxic effects of combination chemotherapy in leukemia.

"Although there is effective chemotherapy for many patients with leukemia, 20% of children and up to 65% of adults relapse. Novel therapies are needed to treat these patients," scientists in the United States reported.

"Leukemia cells are very sensitive to the proteasome inhibitor bortezomib (VELCADE, PS-341), which enhances the in vitro cytotoxic effects of dexamethasone and doxorubicin in multiple myeloma. To determine if bortezomib enhances the cytotoxicity of agents used in leukemia, we employed an in vitro tetrazolium-based colorimetric assay (MTT) to evaluate the cytotoxic effects of bortezomib alone and in combination with dexamethasone, vincristine, doxorubicin, cytarabine, asparaginase, geldanamycin, trichostatin A, and the bcl-2 inhibitor HA14.1," explained T.M. Horton and colleagues, Baylor College of Medicine.

"We demonstrated that primary leukemia lymphoblasts and leukemia cell lines are sensitive to bortezomib, with an average IC50 of 12 nM. Qualitative and quantitative bortezomib-drug interactions were evaluated using the universal response surface approach (URSA). Bortezomib was synergistic with dexamethasone in dexamethasone-sensitive leukemia cells, and additive with vincristine, asparaginase, cytarabine, and doxorubicin.

"The anti-leukemic activity of bortezomib was also additive with geldanamycin and HA14.1, and additive or synergistic with trichostatin A. These results were compared to analysis using the median-dose effect method, which generated complex drug interactions due to differences in dose-response curve sigmoidicities," informed the scientists.

The researchers concluded, "These data suggest bortezomib could potentiate the cytotoxic effects of combination chemotherapy in patients with leukemia."

Horton and colleagues published their study in Cancer Chemotherapy and Pharmacology (Bortezomib interactions with chemotherapy agents in acute leukemia in vitro. Cancer Chemother Pharmacol, 2006;58(1):13-23).

For additional information, contact T.M. Horton, Baylor College of Medicine, Texas Children's Cancer Center, 6621 Fannin, MC 3-3320, Houston, TX 77030, USA.

The publisher's contact information for the journal Cancer Chemotherapy and Pharmacology is: Springer, 233 Spring Street, New York, NY 10013, USA.

Keywords: Houston, Texas, United States, ALL, AML, Asparaginase, Bortezomib, Chemotherapy, Cytarabine, Dexamethasone, Diagnostics, Doxorubicin Hydrochloride, Drug Interactions, Cancer Drugs, Leukemia, Multiple Myeloma, Oncology, Pharmaceuticals, Pharmacokinetic, Synergy, Cancer Therapy, VELCADE, Vincristine.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.