Two phase I studies of carboplatin dose escalation in chemotherapy-naive ovarian cancer patients supported with granulocyte-macrophage colony-stimulating factor.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) may reduce myelosuppression and, thus, allow dose escalation of certain chemotherapeutic agents. We conducted two sequential phase I trials of escalating doses of carboplatin and a fixed dose and schedule of rHuGM-CSF in ovarian cancer patients who had not previously had chemotherapy, i.e., chemotherapy-naive patients. In the first trial, patients were assigned to regimens of increasing dose levels of carboplatin (starting at 400 mg/m2) and fixed doses and schedules of cyclophosphamide (600 mg/m2) and rHuGM-CSF (10 micrograms/kg given subcutaneously once daily on days 2-11). Chemotherapy was given every 3 weeks (regimen A). In the subsequent trial, the design was the same except that cyclophosphamide was omitted (regimen B). Fifteen patients received regimen A, and seven patients received regimen B. In regimen A, all three patients treated at the first dose level tolerated five cycles at full doses. Hematologic toxicity was dose limiting at the 600-mg/m2 dose level. When 500 mg/m2 carboplatin was given, six of eight patients tolerated three or four cycles at full doses before requiring dose reductions or treatment delays. In regimen B, doses could not be escalated above the first dose level (600 mg/m2) because of severe hematological toxicity. Nonhematological toxicity was tolerable and managed with acetaminophen, antihistamines, and/or nonsteroidal, anti-inflammatory medication. Compliance was excellent. We conclude that (a) rHuGM-CSF can be given safely and reliably to chemotherapy-naive ovarian cancer patients receiving these treatment regimens, (b) early and severe thrombocytopenia was a major problem with or without cyclophosphamide with doses of carboplatin at or above 600 mg/m2, and (c) 500 mg/m2 carboplatin administered every 3 weeks is the highest dose in regimen A that can be given safely in the outpatient setting.

Chronic home care in ontario: five year follow up.

The first 218 patients admitted to the Kingston Chronic Home Care program (CHC) after its inception in October, 1975 were followed to March 31, 1981. Their average number of admissions to CHC was 2.3, and they averaged 16 months in CHC. Twenty-eight percent died before any admission to a longterm care institution; 44% were admitted to such an institution at or after last separation from CHC. The study suggests that CHC results in a significant degree of prevention or delay of admission to institutions.

Factors predictive of survival after first relapse or progression in advanced epithelial ovarian carcinoma: a prediction tree analysis-derived model with test and validation groups.

OBJECTIVE: To identify factors predictive of overall survival after first relapse or primary progression in patients with advanced epithelial ovarian cancer. METHODS: "Tree-structured prediction of survival for censored survival data" was used to identify the independent prognostic factors in the test group (n = 352) who were the patients from the previously reported Canadian OV.8 trial. A prognostic model was developed using these factors and subjected to validation in the Canadian OV.4 trial cohort (n = 282). RESULTS: Based upon three factors, time from diagnosis to first recurrence or progression, tumor grade at diagnosis, and ECOG performance status at original diagnosis, three groups of patients were identified. These were labeled as good, intermediate, and poor prognosis with median survivals post relapse of 18 (12), 6 (5), and 1 (2) months, respectively. The figure in parentheses is the survival in the validation cohort. CONCLUSIONS: These prognostic groupings enable us to recommend second-line treatment more logically. The patients in the poor prognosis group have such a limited survival that cancer shrinking therapy should not routinely be offered. In addition the use of the individual predictive factors as stratification factors will help to avoid erroneous conclusions about treatment efficacy.