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Background. Paclitaxel is a diterpenic plant product that has significant activity in several solid tumors, including epithelial ovarian cancer. After promising results in Phase I and II studies, its use has increased dramatically. With this increased use, isolated reports of local tissue reactions to paclitaxel have been described. The purpose of this study was to characterize further the presentation and clinical course of this toxic effect. Methods. Nine hundred fifty-five courses of paclitaxel were administered to patients with gynecologic malignancies at M.D. Anderson Cancer Center during a 13-month period. Nineteen (2%) local infusion-site injuries in 17 patients were observed. Results. The primary disease site was the ovary in 13 patients, the peritoneum in 2, and the endometrium in 2. Paclitaxel was administered as initial therapy in 6 patients and as salvage therapy in 11. Clinical evidence of infiltration was documented during infusion in 8 of 19 (42%) reported episodes. Immediate reactions consisting of mild discomfort, erythema, and edema were observed in six patients, three of whom had complete resolution of the lesion within 1 month. The remaining patients noted initial development of injury between 3 and 13 days after paclitaxel infusion. The typical injury was a discolored, raised, rounded, and indurated lesion that was moderately painful. Two patients (11%) had Grade 1 lesions, 13 (68%) had Grade 2 lesions, and four (21%) had Grade 3 lesions with central ulceration. Cellulitis requiring intravenous antibiotic therapy was associated with two discoloration and induration; one patient had persistent ulceration present at the time of her death 6 months after presentation and one patient underwent excision of a persistant lesion at 12 months. Conclusion. Given the incidence of Grade 2 and Grade 3 local reactions, it appears that paclitaxel should be considered a vesicant. Cancer 1995; 76:116-20. Key words: paclitaxel, extravasation, infiltration, vesicant.

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]

Background. In the treatment of advanced-stage ovarian cancer, it is common practice to treat elderly patients in a less aggressive fashion than young patients. This approach is based on the notion that age is associated with poor patient tolerance to aggressive chemotherapy. Relatively little data exist to support this contention. The most exciting new chemotherapy agent to be developed in the last 10 years is taxol, a diterpeniod derivative of the Northwestern yew Taxus brevifolia. Methods. The ability to administer dose-intensive taxol to adult patients with recurrent ovarian cancer was assessed retrospectively, and the question was asked whether the administered dose intensity of taxol was unfavorably influenced by age. Forty-eight patients with recurrent ovarian carcinoma received taxol at an initial dose of 250 Mg/[m.sup.2] every 3 weeks. Age in this cohort ranged from 26 to 74 years, with a median of 55. Twenty-nine percent (14 of 48) of the patients treated were 61 years of age or greater. Criteria for administration of taxol included a creatinine clearance of > 45 ml/minute, minimal abnormalities in liver function tests, good performance status, and the absence of substantial comorbid disease. Results. Elder y patients in this cohort (age > 60 years) did not differ from younger patients with respect to administered dose intensity, number of cycles of therapy administered, or the occurrence of serious or mild toxicities. Conclusions. Age, in and of itself, should not be a factor in the consideration of dose modifications of taxol. Cancer 1993; 71:594-600.