FORT LAUDERDALE, Fla--There still is insufficient evidence about the use of high-dose chemotherapy plus bone marrow or peripheral stem cells to support its inclusion as a path on the updated National Comprehensive Cancer Network (NCCN) practice guidelines on breast cancer, said panel chair Robert W. Carlson, MD, at the NCCN's second annual conference.
"The role of high-dose chemotherapy continues to be controversial because there is so very little data on it," Dr. Carlson said in an interview. "This is one of the areas of the guidelines that will have to be looked at every single year."
Although the role of high-dose chemotherapy remains contentious, the debate over how to handle this therapy in the NCCN guidelines has been resolved, at least for the moment.
At a special meeting convened after the first NCCN conference, the breast cancer guidelines panel and representatives from the bone marrow transplantation committee agreed that, until more definitive data become available, high-dose chemotherapy should still be relegated to a footnote.
NCCN Breast Cancer Guidelines Panel
Robert W. Carlson, MD
Lori J. Goldstein, MD
William J. Gradishar, MD
Allen S. Lichter, MD
Beryl McCormack, MD
Roger E. Moe, MD
Richard L. Theriault, DO
The wording of that footnote, however, has been changed to highlight three "special situations" in which participation in a clinical trial of high-dose therapy is "especially appropriate": women with 10 or more positive nodes, those with locally advanced (stage IIIB) disease, and those with metastatic or recurrent disease.
More Specific Adjuvant Therapy
The revised guidelines contain other substantive changes from the earlier version, said Dr. Carlson, of Stanford University Medical Center. The most significant changes relate to adjuvant therapy for women who have node-negative disease and relatively small tumors, a group with an excellent prognosis overall.
"The changes in the current guidelines were designed to identify subsets of women within that overall prognostic category who may have a prognosis that is less favorable than other women in that group, and who may benefit, in a meaningful way, from adjuvant chemotherapy," Dr. Carlson said.
"Previously, we simply lumped all tumors less than 1 cm in size together and said that no adjunctive therapy was appropriate," Dr. Carlson noted. Now, however, the guidelines stratify both the unusual and usual tumor histologies by size, with treatment recommendations varying depending on histology, size, and other prognostic features.
For unusual histologies that have a particularly favorable prognosis, such as tubular, colloid, medullary, and adenocystic tumors, adjuvant therapy is not recommended if the tumor is less than 1 cm, whereas such therapy should be considered if the tumor is between 1 and 2.9 cm, and is deemed appropriate if the lesion is 3 cm or larger.
For the usual histologies of ductal or lobular invasive carcinoma, the updated guidelines do not recommend adjuvant therapy if the tumor is between 0.5 and 0.9 cm in size and has no unfavorable features (eg, angiolymphatic invasion, high S-phase, high histologic or nuclear grade). If those poor prognostic features are present, adjuvant therapy should be considered, although Dr. Carlson pointed out that the panel labeled this recommendation controversial (category 2).
Categories of Acceptability for Guideline Recommendations
Category 1: Recommendations that are uncontested and generally accepted by all authorities in that particular cancer
Category 2: Recommendations that are somewhat controversial
Category 3: Items that will require further analysis for firm recommendations
Category 4: Recommendations that caused real disagreements among members of the NCCN panel
For women under age 50 years with receptor-positive ductal or lobular carcinomas, the guidelines have been altered such that tamoxifen(Drug information on tamoxifen) (Nolvadex) or chemotherapy is endorsed if the tumor is 1 to 3 cm, and chemotherapy with or without tamoxifen is recommended if the tumor is greater than 3 cm.
The updated guidelines also provide more specific adjuvant therapy recommendations for women with node-positive disease. "We felt that, for women with one to three involved lymph nodes with negative hormone receptors, adjuvant chemotherapy was appropriate," Dr. Carlson said.
Among women with one to three positive lymph nodes and receptor-positive disease, adjuvant chemotherapy with or without tamoxifen is deemed appropriate for those under age 50, whereas tamoxifen with or without chemotherapy should be considered for those age 50 or older. The panel felt that the use of chemotherapy in older women was a controversial (category 2) recommendation, he added.
For younger women with four or more positive nodes, regardless of receptor status, adjuvant chemotherapy is recommended, with the addition of tamoxifen deemed "optional" for those with receptor-positive tumors. In older women with four or more involved nodes, adjuvant chemotherapy is advocated for those with receptor-negative tumors, and tamoxifen with or without chemotherapy for those with receptor-positive disease.
"The forms of adjuvant chemotherapy that we felt were appropriate we actually specified," Dr. Carlson said. While emphasizing that the regimens undoubtedly will be changed as data from new trials become available, he noted that currently, CMF, FAC, CAF, and AC are listed as appropriate choices for women with zero to three positive nodes, and the same combinations plus the Milan regimen (Adriamycin followed by CMF) are recommended for those with four or more positive nodes.