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11 - Gleevec: From Broken Chromosomes to Precision Cancer Therapy

Published online by Cambridge University Press:  19 January 2018

Philip A. Rea
Affiliation:
University of Pennsylvania
Mark V. Pauly
Affiliation:
University of Pennsylvania
Lawton R. Burns
Affiliation:
University of Pennsylvania
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Summary

Just 17 years ago, a patient diagnosed with chronic myelogenous (or myeloid) leukemia (CML) faced a grim future. This disease, a bone marrow cancer resulting in excessive production of certain types of white blood cells, usually progresses slowly over the course of several years. It starts with few if any symptoms, then eventually enters an acute phase of rampant, uncontrolled white blood cell proliferation – known as blast crisis – in which the body's immune system is overwhelmed by the leukemia cells. The treatment options that CML sufferers had at that time, which seldom saved lives, all came with a high physical and emotional penalty to both patient and caregivers. These options included: conventional chemotherapy and all of the usual debilitating complications such as nausea and weight and hair loss; daily interferon infusions that were almost invariably accompanied by severe flu-like symptoms; or bone marrow transplants for the 20–25 percent of patients who were eligible because of age or other factors, which carried great risk and often were fatal. A bone marrow transplant, when it worked, could at least bring about an outright cure. The same could not be said of conventional chemotherapy or interferon infusions; they merely prolonged survival.

Come 2001, the outlook was to change radically for the majority of CML patients. A new precision-targeted drug with the US tradename Gleevec (imatinib mesylate), international tradename Glivec, made its appearance and increased the five-year survival rate for many CML sufferers from only about 30% to an unprecedented 89%. At a daily oral dose of only 400–600 mg, this drug elicited a precipitous decrease of 85% in the number of cells harboring the genetic marker for the disease and a complete remission in 69% of patients, with few side effects. Indeed, Gleevec proved to be so much more effective than interferon that the Phase III clinical trials underway at this time were halted after only 18 months to permit a switch to the new treatment for patients in the interferon arms of the studies.

Gleevec, which started life as the new molecular entity “CGP-57148B,” marked a novel approach to treating CML.

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Managing Discovery in the Life Sciences
Harnessing Creativity to Drive Biomedical Innovation
, pp. 331 - 360
Publisher: Cambridge University Press
Print publication year: 2018

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