Dose-intense Taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer

Background: Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number of solid tumors, including ovarian cancer and breast cancer. Purpose: Our purpose was to conduct a phase 11 clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF). Methods: A prospective phase 11 clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/[m.sup.2] paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 [mu]g/kg per day was given to ameliorate myelosuppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 [mu]g/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy. Results: Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients; 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy. Conclusions: We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower dose in similar cohorts of patients treated without G-CSF. Comparison of phase 11 studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer. [J Natl Cancer Inst 86:18-24, 1994]