A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).

BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.

Hospice care in a long-term skilled-care facility.

Although the acute care hospital cannot provide care for terminally ill patients who are not receiving active therapy, a hospice unit has much to offer such patients. Since the elderly and the chronically ill also can benefit from palliative and supportive care, a long-term skilled-care facility is an ideal setting for a hospice unit. In this article, the authors discuss the various services provided by a hospice unit, where the emphasis is on care rather than cure.

Phase II study of cis-dichlorodiammineplatinum(II) (NSC-119875) in combination with cyclophosphamide (NSC-26271) in the treatment of human malignancies.

The effectiveness of cis-dichlorodiammineplatinum(II) in the treatment of human malignancies is evaluated. The first stage of our investigation consisted of a phase I study to determine toxicity. In the second stage attempts were made to reduce toxicity by varying the modes of administration, and the third stage comprised studies of combination chemotherapy including cis-dichlorodiammineplatinum(II). A total of 74 patients have been treated, 20 of whom received the combination of cis-dichlorodiammineplatinum(II) and cyclophosphamide. Major toxic effects included vomiting, mild leukopenia and thrombocytopenia, decreased creatinine clearance, audiologic toxic effects, hyperuricemia, and nephrotoxicity. Measurable regression of tumors was seen in 18 of the 74 patients and ten of the 18 patients who responded had been given the combination of cis-dichlorodiammineplatinum(ii) and cyclophosphamide.