Chemotherapy has proven to be lifesaving for many cancer patients, but the treatment often inflicts massive "collateral” damage on surrounding healthy cells as the malignancy is being treated. The result can be serious side effects, such as nausea, vomiting and hair loss.
To treat cancer patients more effectively, doctors have recently begun prescribing newly developed "smart" drugs taken as daily pills or intravenously) that precisely target the malignancy through sophisticated molecular processes. The new drug therapy typically results not only in improved outcomes, but also in far fewer serious side effects.
David G. Nathan, MD, a professor at Harvard Medical School and president emeritus of the Dana-Farber Cancer Institute in Boston, one of the world's leading centers for cancer research and treatment, relently shared his insights on the use of smart drugs.
Cancers that may be treated with smart drugs…
About 25% of women with breast cancer have a receptor known as HER2 on the cancer cells. The receptor is activated by a protein called epidermal growth factor (EGF), which speeds up the division of cancer cells, leading to faster-growing, deadlier tumors.
In a landmark study, breast cancer patients with HER2 receptors were treated with either the smart drug transtuzumab (Herceptin) and chemotherapy after surgery, or chemotherapy alone. Those receiving Herceptin had a 52% lower rate for tumor recurrence and a 33% lower risk of dying over a three-year period than women given only standard chemotherapy.
How Herceptin works: It binds to the HER2 receptor and inhibits tumor cell growth. Herceptin may cause mild side effects, such as fever, muscle aches and nausea. (Nausea is milder and less common with smart drugs than with chemotherapy alone.)
Chronic myelogenous leukemia (CML) is a form of leukemia (cancer of blood and bone marrow) that most commonly develops between ages 40 and 60.
In a five-year study of 454 CML patients who were given the smart drug imatinib (Gleevec), 46% survived in complete remission far longer, on average, than those given interferon, a standard therapy for certain cancers.
How Gleevec works: It blocks the signals of a protein (Ber-AbD) that can cause bone marrow to make very high numbers of white blood cells and immature stem cells that crowd out the red blood cells and platelets.
Like many smart drugs, Gleevec usually causes fewer side effects than chemotherapy—because it blocks the action of a specific protein rather than eliminating millions of cancer cells and healthy cells. Gleevec may cause mild side effects, such as swelling around the eyes and muscle cramps.
Problem: Some CML patients become resistant to Gleevec, a problem that has traditionally necessitated a stem cell transplant, a sometimes fatal procedure that can involve high-dose chemotherapy and total body radiation.
Now: CML patients can try newly developed, second-generation smart drugs, such as nilotinib (Tasigna) and dasatinib (Sprycel).
The two main types of lung cancer are non-small-cell and small cell, named according to how the cells look under a microscope. (Nonsmall-cell is the more common form.)
In a recent study, the smart drugs erlotinib (Tarceva) and gefitnib (Iressa) improved survival from 16 years to 3.1 years in the 10% of non-small cell cancer patients who have a particular mutation in a protein that stimulates lung cancer growth.
How Tarceva and Iressa work: Their mechanism of action is similar to that of the breast cancer drug Herceptin. Tarceva may cause mild side effects, such as dizziness and swelling in the hands or feet. Iressa's side effects may include diarrhea, rash and acne.
Non-Hodgkin's lymphoma is a type of lymphoma (cancer of the lymph nodes) that develops in B or T lymphocytes (a type of white blood cell).
An analysis of five clinical studies on follicular lymphoma (a common type of non-Hodgkin's lymphoma) found that 90% of patients who received the smart drug rituximab (Rituxan), along with chemotherapy, survived for three to five years, compared with 80% of patients who had chemotherapy alone.
How Rituxan works: It targets a protein on the surface of the malignant cells that are generated during follicular lymphoma, thus triggering the immune system to attack the cells. Healthy cells are also targeted and attacked, but the body quickly replaces them after the therapy. Rituxan may cause mild side effects, such as headache, cough and skin flushing.
Smart drugs that show promise…
When cancer metastasizes, it spreads beyond the original site to other parts of the body.
In one study, doctors from the University of California at Los Angeles analyzed the results of three studies focusing on the treatment of metastatic colon cancer with the smart drug bevacizumab (Avastin) and chemotherapy, compared with chemotherapy alone. Patients who took the combined treatment survived 179 months, on average, compared with 14.6 months, on average, for those who had only chemotherapy.
How Avastin works: The drug blocks a protein that triggers angiogenesis (formation of new blood vessels- a process that can promote tumor growth). Avastin's potential side effects include tiredness, stomach pain and headache.
Renal cell carcinoma is a malignant tumor of kidney cells that most often develops after age 50.
In a recent study of 903 patients with renal cell carcinoma that was resistant to standard cancer therapy with interferon, half the patients took the smart drug sorafenib (Nexavar for about 19 months and half took a placebo. Sorafenib reduced the risk for death by 28%, with the sorafenib group living an average of 19.3 months, compared with 15.9 months for the placebo group.
How Nexavar works: One of a new class of smart drugs, Nexavar works by inhibiting the proteins inside cancer cells that control cell division...like Avastin, Nexavar also inhibits angiogenesis. Nexavar may cause mild side effects, including skin rash, fatigue and nausea.
How To Find Out More
To find out whether smart drugs are right for you or a family member with cancer-and to learn more about current or future clinical trials with the drugs—talk to an oncologist. Or visit the Web sites of the National Cancer Institute (www.cancer.gov) or the American Cancer Society (www.cancer.org).