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Recurrence, side effect challenges in colon, breast cancer

As more cancer patients survive, internists must be ready to switch gears from treatment to surveillance

From the June ACP Observer, copyright 2006 by the American College of Physicians.

By Deborah Gesensway

As more effective treatments are developed for colon and breast cancer, internists face new challenges. They must now decide how to best screen patients to find early stage disease to take advantage of new treatments. They also have to deal with treating drug side effects—and determine how to best evaluate patients for post-treatment surveillance.

“These are drugs that are proving to be very important for treating cancer, but they are creating diseases in the form of serious side effects,” said Matthew J. Ellis, MD, associate professor of medicine and director of medical oncology at Washington University School of Medicine in St. Louis. He was part of a panel speaking at an Annual Session course entitled “Approach to Common Malignancies: Breast Cancer and Colon Cancer.”

Side effects of new biological therapies range from blindness and hypertension associated with bevacizumab, cardiomyopathy from trastuzumab, rashes and diarrhea due to HER1 and HER2 kinase inhibitors, and osteoporosis associated with aromatase inhibitors.

Internists need to know about these problems because they may be required to assist in patient management when the patient presents acutely. Here are three commonly used drugs and some of their side effects:

  • Bevacizumab (Avastin). This monoclonal antibody can cause mild to moderate high blood pressure that has to be managed based on the patient’s baseline blood pressure. Other possible, though rare, side effects are arterial thromboses and strokes, noted Edith P. Mitchell, FACP, clinical professor of medicine in the division of medical oncology at Thomas Jefferson University in Philadelphia, another session speaker.

    More common, she said, are problems with wound healing. That means patients must wait before having another surgery. “If a patient has been on Avastin, they should not have elective surgery within eight weeks of drug administration,” she said. They should likewise not receive bevacizumab within four weeks of having major surgery.

  • Trastuzumab (Herceptin). This drug is also given as an adjunct to chemotherapy. Its 4% risk of causing cardiomyopathy is “driving our cardiologists crazy,” Dr. Ellis said. Pneumonitis is also a problem, which can be treated by high doses of steroids.
  • Lapatinib (Tykerb). This third adjunct does not seem to have as many side effects, Dr. Ellis said, but there are some patients who experience severe diarrhea while taking it.

Colon cancer update

Ten years ago, the overall survival of patients diagnosed with metastatic colon cancer was between 11 and 12 months; today, survival estimates exceed more than 30 months, Dr. Mitchell said. From the 1950s to the mid-1990s, there was only one drug on the market to treat colon cancer—but since 1996, five have been approved.

That improvement is due not only to improved treatment options for metastatic disease and adjuvant therapy. It is also due to more rigorously screening for the disease and to better staging once it is found, she said.

But problems remain, especially in terms of diagnosing the disease at earlier stages and removing polyps before they become cancerous. Even though African Americans, for example, have a 20% higher chance than Caucasians of developing colon cancer and a 40% higher chance of dying of it, studies have found that African Americans as a group have a “higher incidence of never having undergone colon and rectal cancer screening,” Dr. Mitchell said.

Because blacks develop colon cancer at an earlier age than whites, she pointed out, the American College of Gastroenterology last year recommended that African-American patients undergo screening starting at age 45, rather than age 50.

“We don’t yet understand why this is, but what we see is a higher incidence of poorly differentiated, mucin-producing tumors in African Americans and more tumors with poor prognostic features,” she said.

From research being done on staging, experts now know that these types of tumors have a worse prognosis than others, as do those found in younger patients and on the left side of the colon. Surgeons and pathologists must count lymph nodes in resected specimens and find at least 12-15 to stage the disease accurately.

“For Stage I there is a 97% five-year survival; for Stage II, approximately 85%; for Stage IIIA, about 60%; for Stage IIIC, fewer than 30% are alive at five years,” she said. "Precise and accurate staging is important, not only for determining adjuvant treatment but also for patient prognosis."

In determining a patient's risk for developing colon cancer, the family history— including the history of colorectal and other malignancies— is very important. Additionally, inflammatory bowel disease and a history of pelvic irradiation may increase risk.

Because between 10% and 15% of colon and rectal cancers are hereditary, internists must take detailed family cancer histories. They should also consider referring patients to genetic counseling if they develop colon or rectal cancer before age 50, if they have relatives who developed colon cancer or polyps at a young age, or if they are older than age 50 and have had two or more cancers.

Breast cancer update

When it comes to breast cancer, a history of any cancer cluster—not just breast cancer—may be important, said Dr. Ellis. In addition, people need to realize that they may inherit breast cancer risk from their father, not just their mother.

Genetic testing for BRCA1 and 2 is not perfect, with as many as 12% of mutations being missed, he said. If a patient clearly looks like she has such a mutation even though the test is negative, “you can’t reassure the patient.”

For patients at particularly high risk, he said, prophylactic mastectomy is 95% effective—and MRI screening, rather than mammography, should be offered.

Chemoprevention with tamoxifen posts an impressive 49% reduction, but has its downsides, including thrombosis, endometrial cancer and stroke. Raloxifene appears to cause fewer of these side effects. In addition, he said, aromatase inhibitor drugs may play a role for postmenopausal women surgically treated for early-stage, hormone-responsive breast cancer. (Letrozole, anastrazole and exemestane are FDA-approved.)

“The tendency is to give the new drugs [instead of tamoxifen] unless a patient has very bad bones or a very low risk,” he said. But these new drugs are much more expensive, so one strategy is to prescribe tamoxifen for the first few years and then switch to the aromatase inhibitors.

“There is," Dr. Ellis said, "a risk-benefit balance to work out with all patients.”

Deborah Gesensway is a freelance health care writer in Toronto.

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.

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