National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1-3, 2000.

OBJECTIVE: Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer. PARTICIPANTS: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient representatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000. EVIDENCE: The literature was searched with the use of MEDLINE(TM) for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination.

A phase II trial of intermittent leukocyte interferon and high dose chlorambucil in the treatment of non-Hodgkin's lymphoma resistant to conventional therapy.

Thirteen patients with advanced non-Hodgkin's lymphoma who previously failed conventional chemotherapy protocols were treated with a combination of alpha-interferon (IFN) 6,000,000 units i.m. days 1-5 and 8, plus chlorambucil (CLB) 16 mg/m2 days 5-9 repeated every 4 weeks. There were five complete responses (CRs) and one partial response (PR) (46% total responses) with mean duration of remission of 456+ days. Responses were obtained in low and intermediate grade lymphomas. Toxicity was acceptable and easily managed. It is unlikely that IFN alone using this low dose intermittent schedule is responsible for the remissions. The combination of the two agents appears to be an effective treatment modality. IFN may be functioning as a biological response modifier when used in combination with a cytotoxic agent.

cis-platinum, 5-fluorouracil, and hydroxyurea in the treatment of advanced non-small-cell lung cancer. A phase II study.

Sixteen patients with advanced non-small-cell lung cancer were treated with the combination of cis-platinum, 5-fluorouracil, and hydroxyurea. There were two complete responses (lasting 16 weeks each) and one partial response (lasting 12 weeks). Toxicity was manageable, but responders were unable to tolerate further therapy. Despite the obtaining of complete responses, the overall benefit of this particular combination requires further clinical investigation.

Leukocyte interferon as a possible biological response modifier in lymphoproliferative disorders resistant to standard therapy.

In vitro and in vivo studies utilizing a combination of leukocyte interferon-alpha (IFN) and chlorambucil (CLB) were done to investigate possible synergism between a biological response modifier and a chemotherapy drug. In vitro studies utilized a human myeloid leukemia cell line (K-562) pretreated with IFN and then exposed to CLB. The combination resulted in significant depression of cell growth compared with use of IFN or CLB alone. In vivo studies involved eight heavily pretreated patients given 6 million units IFN for 5 days followed by oral CLB (16 mg/m2) for 5 days repeated every 4 weeks. Three myeloma patients had reduction in immunoglobulins and experienced clinical responses. Three of four patients with Hodgkin's disease responded after relatively short periods of treatment. One patient with a diffuse lymphocytic lymphoma had a complete unmaintained remission lasting 6 months. Toxicity was minimal, with mild fever, nausea, and vomiting. These preliminary studies suggest that IFN may be a biological response modifier when used in combination with a cytotoxic agent.

Immune Hemolytic anemia.

Immune hemolytic anemia is an acquired anemia resulting from the premature destruction of red cells caused by the presence of antibody and/or complement on the red cell surface. The Coombs test, modified and improved, remains the mainstay of diagnosis.

Case report. Brucella canis bacteremia: a case with negative B canis agglutinins.

Naturally acquired Brucella canis infection is believed to be uncommon, but is not readily diagnosed. A 55-year-old woman developed fever, abdominal pain, malaise, weakness, and anorexia eight weeks after her dog delivered stillborn pups. Blood cultures yielded B canis. Specific B canis agglutinins were negative initially and remained negative during convalescence. Therapy with tetracycline and streptomycin was successful but was associated with a probable Jarisch-Herxheimer reaction.