Phase I/II trial of biweekly paclitaxel and cisplatin in the treatment of metastatic breast cancer.

PURPOSE: To determine the maximum-tolerated dose of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) administered biweekly with a fixed dose of cisplatin, to assess the toxicity, and to evaluate the activity of this combination in a phase I/II trial in metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine women with metastatic breast cancer were enrolled; 27 were assessable for response and 29 for toxicity. All but two of the women had received prior adjuvant chemotherapy, with 23 receiving anthracyclines and six previous cisplatin. RESULTS: The initial starting dose of paclitxel 90 mg/m2 and cisplatin 60 mg/m2 became the phase II dose due to dose-limiting neutropenia. Responses were seen in 85% of assessable patients, with three patients (11%) achieving a complete response (CR) and 20 patients (14%) a partial response (PR), for an overall response rate of 85% (95% confidence interval [CI], 66% to 96%). The time to disease progression for patients who achieved a CR was 110 to 200 days, and for those with a PR, it was 96 to 377+ days, with a median time to progression of 7.1 months and a median response duration of 7.9 months. Sites of CR were skin, soft tissue, and lung, and all occurred in women with previous exposure to anthracyclines. Septic events were rare, with two grade 3 infections (7%), only one of which required hospital admission. There were no grade 4 nonhematologic toxicity and minimal grade 3 toxicity. A total of 251 chemotherapy cycles were given -- 16 with paclitaxel alone in five patients. Forty-five percent of patients required dose reductions, while 52% had delays due to neutropenia. CONCLUSION: Biweekly paclitaxel and cisplatin is an active combination in the treatment of metastatic breast cancer, including for patients with previous exposure to anthracyclines.

Treatment of Kawasaki disease.

The epidemiology, etiology, diagnosis, and treatment of Kawasaki disease are reviewed. Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute, usually self-limiting, multiple-organ-system disease of childhood that occurs both epidemically and endemically worldwide. The etiology of the disease is unknown but may involve an infectious agent. To be diagnosed, a patient must be febrile for at least five days and show four of five additional clinical features: bilateral conjunctivitis, changes in the oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. The most important complications are cardiac; patients may develop aneurysms or thrombosis of the coronary arteries or myocarditis. Other complications include arthritis, conjunctivitis, and hydrops of the gallbladder. Aspirin, intravenous immune globulin, corticosteroids, and antithrombotic agents have been investigated for use in the treatment of Kawasaki disease with varying results. Current recommendations suggest therapy with aspirin 80-100 mg/kg/day every six hours for the first 14 days after diagnosis and intravenous immune globulin 400 mg/kg/day for the first four days. The dose of aspirin should then be reduced and continued for six to eight weeks if no coronary artery abnormalities are present. Treatment guidelines for Kawasaki disease are being refined. Current evidence supports early use of aspirin and intravenous immune globulin to prevent cardiac complications.

Guidelines for the optimal management of chemotherapy-induced nausea and vomiting: a consensus.

Nausea and vomiting are the most frequently reported adverse effects of cancer chemotherapy and have a significant impact on patients' daily functioning, quality of life and compliance with chemotherapy. Summarized in this article are the recommendations for the optimal management of nausea and vomiting developed by a multidisciplinary group of health care professionals. Issues relating to chemotherapy-induced nausea and vomiting are discussed; general principles of treatment are reviewed; treatment algorithms based on emetogenicity and types of chemotherapy are presented; and the importance of issues including non-pharmacological approaches, patient education and pharmacoeconomic perspectives are considered. The goal of antiemetic therapy should be no episodes of vomiting or retching and minimal or no nausea. Data from clinical trials support the clear superiority of 5-HT3 receptor antagonists in a variety of clinical situations. Their cost must be considered not only as an isolated item from the institutional perspective, but also from the perspective of the impact of successful therapy on the patient.

A phase I-II study of bi-weekly paclitaxel as first-line treatment in metastatic breast cancer.

BACKGROUND: Single-agent bi-weekly paclitaxel was studied as first-line metastatic treatment for breast cancer in a phase I-II trial. PATIENTS AND METHODS: Thirty-eight women with metastatic breast cancer were enrolled. Thirty-seven are evaluable for toxicity, 35 for response. RESULTS: The MTD was defined at 160 mg/m2 q two weeks with dose limiting toxicity in two patients consisting of hematological toxicity (1) and neurotoxicity (2). Twenty patients were treated at 150 mg/m2, the recommended dose. Response rates were two CRs and nine PRs (overall 61%) at the RD of 150 mg/m2 and three CRs and 11 PRs for an overall RR of 67% for the two top doses. CONCLUSIONS: The good drug tolerance, response rates, and convenience over weekly treatment suggest this may be a worthwhile regimen.