Special Medical Reports - November 1, 1999 - American Academy of Family Physicians

Special Medical Reports

NCCN and ACS Collaborate on a Patient's Version of the NCCN Practice Guidelines for Breast Cancer
Verna L. Rose

The National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS) have unveiled the first-ever patient-friendly version of the NCCN's clinical breast cancer treatment guidelines. The 17-member institutions of the NCCN develop cancer practice guidelines for cancer subspecialists that incorporate the latest clinical advances, patient advocacy and the most cost-effective outcomes. "The NCCN Oncology Practice Guidelines, which now cover more than 95 percent of all cancer patients, have become the treatment standard for oncology professionals," said William T. McGivney, Ph.D., chief executive officer of the NCCN. "We are proud that our collaboration with the ACS will now bring these guidelines to the patients who need them the most."

The mutual goal of the NCCN and ACS is to provide patients and the general public with state-of-the-art cancer treatment information in understandable language. The information is intended to help patients talk to their physicians about their illness.

Topics covered in the guidelines for treatment of breast cancer include the following: types of breast cancer, stages of the disease, medical decisions and treatment options, follow-up and recurrent cancer, important questions for patients to discuss with their physicians, general information about clinical trials and a glossary of terms commonly used in the treatment of breast cancer. The guidelines also offer visual aids, including six algorithms that represent treatment for different stages of breast cancer. The charts show the steps that patients and physicians should take in determining the most effective treatment for the patient.

To obtain copies of the patient versions of the breast cancer guidelines, contact the NCCN at 888-909-NCCN or the ACS at 800-ACS-2345. The guidelines are also on the NCCN Web site (http://www.nccn.org) and the ACS Web site (http://www.cancer.org). The NCCN and the ACS will translate other NCCN clinical guidelines into patient versions.

The following information has been excerpted from the section of the guidelines on the treatment of stage I and stage II breast cancer. Tumors in stage I breast cancer measure smaller than 2 cm in diameter, and the cancer does not appear to have spread beyond the breast. Tumors in stage II breast cancer measure larger than 2 cm in diameter, and/or the cancer has spread to lymph nodes under the arm on the same side as the breast cancer. Lymph nodes in stage II have not adhered to one another or to the surrounding tissues, a sign that the cancer has not yet advanced to stage III.

For stages I and II breast cancer, the guidelines recommend a work-up that includes the following: blood cell counts and chemical tests; mammography of both breasts; pathology review (i.e., a second opinion on the biopsy sample); estrogen/progesterone-receptor tests to determine if the tumor is hormone-driven, and to what extent; a HER-2/neu test to help predict the response to certain drugs; S-phase or other test of the biopsy to determine how fast the tumor cells are dividing; and a bone scan, if warranted.

The preferred treatment for most women with stage I or stage II breast cancer is breast-conserving therapy in the form of a lumpectomy with removal of underarm lymph nodes, followed by radiation therapy (see algorithm on primary treatment for stage I and stage II breast cancer). Decisions about adjuvant chemotherapy or hormonal therapy are based on the status of axillary lymph nodes, the size of the cancer and its histologic type. The guidelines have additional algorithms for adjuvant treatment in stages I and II breast cancer; stage III breast cancer; follow-up of stages I, II and III breast cancer, and work-up and treatment of recurrence; and stage IV (metastatic) breast cancer.

The guidelines also state that participation in a clinical trial is appropriate for women with breast cancer at any stage. In women who have 10 or more positive nodes, the NCCN believes that participation in a clinical trial for high-dose chemotherapy with bone marrow transplantation is especially appropriate.

Algorithm for Primary Treatment of Stages I and II Breast Cancer

Reprinted with permission from the National Comprehensive Cancer Network and the American Cancer Society. Breast cancer treatment guidelines for patients. Http://www.cancer.org. Retrieved March 1, 1999.

The member institutions of the NCCN are Arthur G. James Cancer Hospital and Research Institute at Ohio State University, Columbus, Ohio; City of Hope National Medical Center, Los Angeles; Dana-Farber Cancer Institute, Boston; Fox Chase Cancer Center, Philadelphia; Fred Hutchinson Cancer Research Center, Seattle; Huntsman Cancer Institute at the University of Utah, Salt Lake City; The Johns Hopkins Oncology Center, Baltimore; University of Texas M.D. Anderson Cancer Center, Houston; Memorial Sloan-Kettering Cancer Center, New York City; Northwestern University/Lurie Comprehensive Cancer Center, Chicago; Roswell Park Cancer Institute, Buffalo; St. Jude Children's Research Hospital, Memphis; Stanford University Medical Center, Stanford, Calif.; The University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham; University of Michigan Comprehensive Cancer Center, Ann Arbor, Mich.; and UNMC/Eppley Cancer Center at the University of Nebraska Medical Center, Omaha.

ACIP Issues Recommendations for Lyme Disease Vaccine
Sharon Scott Morey

Recommendations for the use of the Lyme disease vaccine (Lymerix) have been issued by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC). The recommendations were reported in the June 4, 1999, issue of Morbidity and Mortality Weekly Report (vol. 48, no. RR-7).

In addition to information about the vaccine, the report includes a discussion of the epidemiology, clinical features, diagnosis, treatment and prevention of Lyme disease. An appendix to the report shows how Lyme disease risk is measured as a function of entomologic risk and human exposure.

According to the CDC, the number of cases of Lyme disease reported annually in the United States has increased 25-fold since national surveillance of the disease began in 1982. From 1993 through 1997, a mean of 12,451 cases were reported annually to the CDC. Cases occur primarily in the northeastern United States, the mid-Atlantic region, the upper north-central United States (mainly Wisconsin) and in several areas in northwestern California.

The ACIP recommendations for the Lyme disease vaccine are summarized in the accompanying table. According to ACIP, the decision to administer the vaccine should be based on the individual's risk of being bitten by an infected tick. Risk assessment includes consideration of the geographic distribution of Lyme disease and the person's risk of prolonged exposure to the habitat of infected ticks.

The following highlights the information on the mechanism of action, safety, efficacy and immunogenicity of the Lyme disease vaccine.

Mechanism of Action

The Lyme disease vaccine uses recombinant Borrelia burgdorferi lipidated outer-surface protein A (rOspA) as immunogen. Each 0.5-mL dose of the vaccine contains 30 µg of purified rOspA lipidated protein.

Studies in animals indicate that B. burgdorferi in a vector tick undergoes substantial antigenic change between the time of tick attachment on a mammalian host and subsequent transmission of B. burgdorferi to the host. Spirochetes residing in the tick gut at the beginning of tick feeding express primarily OspA. As tick feeding ensues, the expression of outer-surface protein C (OspC) is increased, and the expression of OspA is decreased. Thus, spirochetes that reach the mammalian host after passing through the tick salivary glands express primarily OspC. The vaccine might exert its principal effect by eliciting antibodies that kill Lyme disease spirochetes within the tick gut.

Safety

A randomized, placebo-controlled phase 3 trial included 10,936 subjects who ranged from 15 to 70 years of age and lived in areas where Lyme disease is endemic. The subjects were recruited at 31 sites; 5,469 received at least one 30-µg dose of the vaccine, and 5,467 received at least one placebo injection. Follow-up lasted 20 months.

The most frequent adverse event was soreness at the injection site, which was reported in 24.1 percent of the vaccine recipients. Fewer than 2 percent of the subjects in the vaccine group and the placebo group reported redness and swelling at the injection site. Myalgia, influenza-like illness, fever and chills were more commonly reported by vaccine recipients than placebo recipients, but no more than 3.2 percent of the subjects reported these symptoms. No statistically significant difference was noted between the vaccine and placebo recipients in the incidence of adverse events more than 30 days after a vaccine administration. No differences in the incidence of neurologic or rheumatologic disorders were found among vaccine and placebo recipients during the 20 months of follow-up.

The phase 3 trial also showed that the incidence of adverse events among vaccine recipients who were seropositive at baseline was similar to that among those who were seronegative. In addition, evaluation of safety in 30 patients with a history of Lyme disease revealed no serious adverse events. The safety of three different dosage strengths was evaluated in this uncontrolled safety and immunogenicity trial.

Efficacy and Immunogenicity

Vaccine efficacy (i.e., protection against "definite" Lyme disease) in the phase 3 trial was 49 percent after two doses and 76 percent after three doses. (Definite Lyme disease was defined as the presence of erythema migrans or objective neurologic, musculoskeletal or cardiovascular manifestations of Lyme disease, plus laboratory confirmation of infection.) Efficacy in protecting against asymptomatic infection (i.e., Western immunoblot seroconversion) was 83 percent in the first year and 100 percent in the second year.

Immunogenicity was studied in a group of the adult subjects in the phase 3 clinical trial. One month after the second dose, the geometric mean antibody titer (GMT) of IgG anti-OspA antibodies was 1,227 ELISA units per mL. Ten months later, the GMT had declined to 116 ELISA units per mL. One month after the third injection (month 13), the mean GMT was 6,006 ELISA units per mL, which then declined to 1,991 ELISA units per mL by month 20. Data from the manufacturer indicate that a titer of more than 1,200 ELISA units per mL confers protection against Lyme disease.

Summary of ACIP Recommendations for Use of the Lyme Disease Vaccine

Circumstance
Vaccination Recommendation

Persons who reside, work or recreate in areas of high or moderate risk

Persons 15 to 70 years of age whose exposure to tick-infested habitat is frequent or prolonged Should be considered

Persons 15 to 70 years of age who are exposed to tick-infested habitat, but whose exposure is not frequent or prolonged May be considered

Persons whose exposure to tick-infested habitat is minimal or none Not recommended

Persons who reside, work or recreate in areas of low or no risk Not recommended

Travelers to areas of high or moderate risk

Travelers 15 to 70 years of age whose exposure to tick-infested habitat is frequent or prolonged Should be considered

Children <15 years of age Not recommended

Persons >70 years of age No available data

Pregnant women

Health care providers are encouraged to register vaccinations of pregnant women by calling SmithKline Beecham Pharmaceuticals at 800-366-8900, x 5231

Persons with immunodeficiency No available data

Persons with musculoskeletal disease Limited available data

Persons with previous history of Lyme disease

Persons 15 to 70 years of age with previous uncomplicated Lyme disease who are at continued high risk Should be considered

Persons with treatment-resistant Lyme arthritis Not recommended

Persons with chronic joint or neurologic illness related to Lyme disease and persons with second- or third-degree atrioventricular block No available data

Other recommendations

Vaccine schedule: Three doses administered by intramuscular injection--initial dose, followed by a second dose one month later, followed by a third dose 12 months after the first dose. Administer the second dose (year 1) and third dose (year 2) several weeks before the beginning of the disease transmission season, which is usually April.

Boosters: Existing data indicate that boosters might be needed, but additional data are required before recommendations can be made regarding booster schedules.

Simultaneous administration with other vaccines: Additional data needed; if simultaneous administration is necessary, use separate syringes and separate injection sites.

Adapted from Centers for Disease Control and Prevention. Recommendations for the use of Lyme disease vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-7):1-25.

Copyright © 1999 by the American Academy of Family Physicians.
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