High-Dose Imatinib Appears to Speed Tumor Reduction

Last Updated: 2009-09-21 13:35:14 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - In newly diagnosed chronic-phase chronic myeloid leukemia (CML), high-dose imatinib appears to reduce tumor burden more quickly than does a standard dose, according to a report in the August 31st Journal of Clinical Oncology.

"Most patients can take higher doses well," Dr. Jorge E. Cortes from The University of Texas M. D. Anderson Cancer Center in Houston told Reuters Health by email. "Although these are not standard doses it emphasizes that adequate dosing should be pursued in all patients to optimize the benefit, keeping in mind that mere control of the blood counts is not enough if one is to look for the best long-term outcome for patients."

Dr. Cortes and colleagues investigated the effects of imatinib 400 mg twice daily as initial therapy in 115 patients with newly diagnosed Philadelphia chromosome-positive or Philadelphia chromosome-negative BCR-ABL-positive early CML in chronic phase.

The multicenter study was known as the Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) trial.

Major molecular responses were achieved by 48% of patients by 6 months, 54% by 12 months, and 63% by 18 months, according to the report. Complete molecular response rates were 39%, 44% and 55% at 6, 12 and 18 months, respectively.

Major molecular response was achieved in a median of 8.3 months and complete molecular response in a median of 9.7 months. A complete hematologic response was maintained by 93% of evaluable patients at 18 months, at which point the actual rate of major cytogenetic response was 96% and the rate of complete cytogenic response was 83%.

Acknowledging that the real value of high-dose versus standard-dose therapy cannot be established "without a head-to-head, randomized clinical trial" and that "response rates are lower on an intention to treat analysis," the researchers nevertheless cite several possible advantages for their protocol over historic protocols that might be inferred from their findings, including faster molecular and cytogenic response rates.

In addition, compared with historical controls, twice-daily imatinib was associated with somewhat higher rates of nonhematologic grade 3/4 adverse events and thrombocytopenia, but grade 3/4 neutropenia and anemia rates were similar.

"Randomized studies comparing directly standard versus high-dose imatinib have been initiated," Dr. Cortes said. "Some have been completed and others will be soon."

"However," Dr. Cortes concluded, "the real impact higher doses may have on long-term outcome will take a few years to be fully known."

Several of the paper""s authors receive compensation from and own stock in Novartis, which markets imatinib in the US as Gleevec. In addition, Novartis provided the researchers with medical writing assistance and editorial support.

Source:

J Clin Oncol 2009.


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