I am Dr. Mahesh Pandey. I am a Hematologist and Oncologist at St. Mary’s. I shall be writing about the new exciting developments in cancer treatment. While cancer care remains a big challenge, new developments in diagnosis and treatment have changed the course of some diseases. Better understanding of disease mechanisms and developments of targets to treat changes that are responsible for development of a cancer has led to some breakthrough developments.
One such treatment is the medication Gleevec or Imatinib. Chronic myeloid leukemia (CML) is a cancer of the white cells in which the cells in different stages of development pack up the bone marrow and cause a high white blood cell count, enlarge the spleen, give the sensation of being full after eating small amounts of food, and weight loss. This starts as a gradual disease but untreated, goes into a rapidly progressive phase and eventually transforms into an acute leukemia.
Traditionally the only treatment known for this disease was a bone marrow transplantation, which even in healthy young adults has a death rate of 15%. Additionally, there are longstanding complications even after a successful transplantation. The chemotherapy that was used to treat this disease had a lot of side effects. It was toxic and only palliated this disease for a while and eventually the disease took its course. Another treatment called hydroxyurea only controlled the white cells for a while but did not change the course of the disease at all.
In 1960, a genetic abnormality called Philadelphia chromosome was discovered by Peter Novell in the city of Philadelphia (thus the name of this chromosome) in this disease. The Philadelphia chromosome occurs when a broken piece chromosome number 9 joins with a broken piece of chromosome number 22 and causes uncontrolled proliferation of white cells.
Initially treatment of cancers was focused on treatment of the different stages of the cell cycle. As new chemotherapy agents known to target different stages of cell cycle, attempts were then made to combine chemotherapies that targeted growth of cancer cells at different stages of the cell cycle. Some rapidly growing cancers such as ALL in children, testicular cancer and some aggressive lymphomas can be treated with curative intent with a multi-agent chemotherapy regimen, and the idea was that the different chemotherapy agents each attack the cancer cells at a different stage of cell growth and were able to kill the cancer cells completely in these different diseases and we the cancer could be cured. This approach does not work in majority of cancers since in most cancers only some cells are in the actively dividing phase and most of the cancer cells are in the dormant phase, so chemotherapy is not completely effective. In lymphomas or testicular cancer vast majority of the cells are rapidly dividing so chemotherapy is highly effective.
Now, we are in a new era of targeted therapy. Even though we have known about the Philadelphia chromosome since the 60s, a drug to target the changes caused by Philadelphia chromosome wasn’t discovered until the 1990s. That drug, called Gleevec won FDA approval in 2001. Now, patients with CML that have the Philadelphia chromosome, can be successfully treated. Studies have shown the Gleevec not only normalizes blood count and spleen size, but the changes caused by the Philadelphia chromosome can be removed from the bone marrow (so called molecular response or cytogenetic response). With just the use of Gleevec, patients with CML are now living normal lives. At this point we do not know how long people should stay on the drug but the current standard of care is to maintain patients on Gleevec indefinitely. In terms of side effects, they include diarrhea, nausea, vomiting, mouth sores, swelling, and skin rash. In general, Gleevec is very well tolerated and the side effects are manageable. The only caveat is that 5% of patients with CML do not have the Philadelphia chromosome and, therefore, cannot be treated with Gleevec.
With development of one target Gleevec, better targets against the Philadelphia chromosome have been developed such as new sister drugs Dasatanib and Nilotinib. Now we have more targeted treatment in our arsenal against what was previously thought to be the fatal disease chronic myeloid leukemia.
Gleevec can also act against certain targets on a rare cancer called gastrointestinal stromal tumor or GIST. GIST is known to be a fatal disease if untreated. In its localized form surgery is curative, but in high risks cases, Gleevec adds to the curative intent when used for a year after surgery. In patients where GIST has spread, Gleevec is known to shrink the disease considerably and often completely. Although not curative, it has provided patients with some longevity and quality of life.
Stay tuned for more exciting developments in treatment of cancer.
