Phase II study of docetaxel in patients with liver metastases from breast cancer. UK study group.

BACKGROUND: Previous phase II studies of docetaxel have indicated that hepatic metastases from breast cancer respond well to first-line treatment with docetaxel. The objective of this prospective, open label phase II study therefore was specifically to evaluate the activity and safety of docetaxel in this indication. PATIENTS AND METHODS: The study recruited 47 women (mean age 50 years, range 33-66 years) with hepatic metastases from breast cancer who fulfilled the eligibility criteria. After premedication with steroids, patients received a one-hour intravenous infusion of docetaxel 100 mg/m2 at three-weekly intervals for up to eight cycles. Response to treatment during medication was assessed after three, six and where appropriate, eight cycles and every three month follow-up thereafter, until disease progression or death. RESULTS: The best overall response rate (ORR) for evaluable patients was 64.3% (95% CI: 48.0-78.5%). In terms of the primary efficacy parameters, the ORR at the sixth cycle of treatment was 62% (95% CI: 45%-80%) with 17% complete responses. The median duration of response was 139 days (95% CI: 111-216 days) and the median survival duration calculated on an intent-to-treat basis was 335 days (227-568 days, 95% CI). One (2%) toxic death was reported. CONCLUSIONS: Docetaxel is a highly effective cytotoxic agent in the treatment of patients with liver metastases from breast cancer.

Docetaxel and cisplatin in combination as first-line chemotherapy for advanced epithelial ovarian cancer. Scottish Gynaecological Cancer Trials Group.

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m(2) and docetaxel 75 mg/m(2)); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m(2) and docetaxel 85 mg/m(2)). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m(2) and 75 mg/m(2), respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m(2) adds unacceptable hematologic toxicity and potential risks to the patient.

Docetaxel in the community setting: an analysis of 377 breast cancer patients treated with docetaxel (Taxotere) in the UK. UK Study Group.

BACKGROUND: Given as first- or second-line chemotherapy docetaxel appears to have great potential in advanced breast cancer. PATIENTS AND METHODS: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1-7). 342 patients (91%) had at least one prior anthracycline-based regimen. RESULTS: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients. 46% among the 299 patients who were anthracycline resistant and 35% among the 82 patients who were anthracycline refractory (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan-Meier survival analysis yielded a median survival of 194 days (95% CI: 178-218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. CONCLUSIONS: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.