Chemotherapy Tag Team

Chronic myelogenous leukemia treatment nilotinib and imatinib alternation therapy

(RxWiki News) Drug resistance remains a significant problem in cancer treatment. The contrast of smashing success early on makes any treatment failure later on even more baffling.

A group of scientists had the idea of switching from one drug to another in cycles during cancer treatment for chronic myelogenous leukemia (CML), in the hope that it would reduce the odds of complete resistance developing.

"Ask your oncologist about alternating therapies."

Researchers from the Department of Hematology and Oncologic Sciences at the University of Bologna in Italy conducted a study with Gleevec (imatinib) and Tasigna (nilotinib) -- both in the same class, designed to eradicate similar molecular targets in cancers.

The full presentation of the data from their study, a phase II trial on Gleevec and Tasigna, was presented at the annual meeting of the American Society of Hematology. Researchers showed that this tag-team approach worked, with response rates as good as, if not better than using either drug alone for the entire time.

Despite the good response, the research team had higher hopes, and said that the results were slightly less successful than expected.

Researchers noted that the trial results could have been affected by treating patients with advanced CML, with nearly 70 percent of the enrolled patients formally classified as having medium or high risk CML.

While the latest generation of CML drugs are more effective than either Gleevec or Tasigna, the principles of alternating therapy are worth investigating considering how frequently leukemias become resistant to treatment.

The study design had 123 patients and included an average of 21 months of observation following treatment, which itself consisted of 24 months in total.

The response to treatment was 82 percent at 12 months, which was the result of a steady increase from the initial 59 percent response observed at 3 months after therapy began.

Four patients also showed evidence for a minor change in the electrical activity of the heart.

One of the potential problems involved in switching from one drug to another would be a lag in treatment response, causing a drop in effectiveness each time the drugs were switched. No proof of any lag effect was found, and the results were as good as a continuous therapy with a single drug.

Another worry was that the individual side effects of each drug would multiply rather than simply add up, resulting in far worse toxicity when both were given to patients. No proof of that was found either.

While the most important consideration for the study was finding toxic interactions between the two drugs, side effects were no worse than seen in studies using only one of the drugs, consisting mostly of skin rashes, fluid retention, itching, and minor alterations in liver function.

“The use of more than one tyrosine kinase inhibitor may reduce the incidence of resistance, [and] the sequential administration is one of the several ways of exploring this strategy.” stated Fausto Castagnetti, MD, an oncologist from the University of Bologna in Italy.

Researchers disclosed financial relationships with Bristol-Myers Squibb, Novartis Pharma and ARIAD.

Research presented at conferences and findings should be considered preliminary until publication in a peer-reviewed journal.

Review Date: 
June 14, 2012