NIH consensus development statement on hydroxyurea treatment for sickle cell disease.

National Institutes of Health consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of (1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), (2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, (3) questions and statements from conference attendees during open discussion periods that are part of the public session, and (4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the U.S. Government.The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.

Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58.

Based on the recommended phase II doses for doxorubicin (60 mg/m2) and docetaxel (60 mg/m2) and the National Surgical Adjuvant Breast and Bowel Project's (NSABP) experience with doxorubicin and cyclophosphamide (cyclophosphamide 600 mg/m2), we conducted a phase II trial at 18 institutions using doxorubicin/docetaxel/cyclophosphamide (ATC) given every 21 days, in preparation for a major adjuvant breast cancer study (NSABP B-30), in which ATC would be used. Eligibility requirements included measurable stage IIIB/IV breast cancer, performance status 0-2, normal left ventricular ejection fraction, and no prior chemotherapy for metastatic disease (nontaxane adjuvant chemotherapy was allowed if completed > 12 months before entry and if the cumulative dose of doxorubicin was =240 mg/m2). Eighty-nine patients were entered who ranged in age from 30-78 years (38.2% < 50 years; 61.8% =50 years). A total of 33.7% of patients had stage IIIB disease, and 66.3% had stage IV disease. Among the stage IV patients, 20.3% had received prior adjuvant chemotherapy. Dexamethasone premedication (8 mg p.o. b.i.d. for 3 days) and prophylactic ciprofloxacin (500 mg p.o. b.i.d. days 5-15) were used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in a prior cycle. After a cumulative dose of doxorubicin 480 mg/m2, patients could continue with docetaxel/cyclophosphamide alone. Eighty-nine patients and 577 courses were evaluable for toxicity. Median time on study as of May 2002 was 36.5 months (range, 28-47 months). Febrile neutropenia occurred in 34 patients (38%); 8 developed FN in the absence of prior prophylactic growth factor support; 26 developed FN despite prior growth factor support (for one patient this information was unavailable). There were no septic deaths. One patient died from pulmonary embolism. Other grade 3/4 adverse events included: nausea (9%), vomiting (7%), stomatitis (6%), diarrhea (4%), arthralgia/myalgia (3%), and neurotoxicity (1%). Clinical congestive heart failure was seen in 3 patients (3.4%). Seventy-seven patients were evaluable for best response within 6 cycles of therapy. Thirteen patients (16.9%) had a complete response, 43 (55.8%) had a partial response, for an overall response rate of 72.7%. The median response duration was 23.8 months (95% CI, 16.2-37.8 months), and the median time to progression or death was 23.5 months (95% CI, 16.3-38.7 months). The median survival time was 35.6 months (95% CI, 26.6-39.4 months). The administration of ATC with primary ciprofloxacin and secondary colony-stimulating factor prophylaxis is feasible and active. Its value in the adjuvant setting is currently under investigation.