Related Experiment Videos
Docetaxel: an active new drug for treatment of advanced epithelial ovarian cancer
M J Piccart1, M Gore, W Ten Bokkel Huinink
1Jules Bordet Institute, Brussels, Belgium.
Background:
Because of the relative scarcity of natural paclitaxel (Taxol), which has been recently recognized as a highly cytotoxic agent for use in platinum-refractory ovarian cancer, synthetic and semisynthetic substitutes have been actively pursued. Docetaxel (Taxotere), a new semisynthetic taxoid, has been selected for clinical development because it is twice as potent as paclitaxel in promoting assembly of tubulin and in inhibiting microtubule depolymerization. Docetaxel also shows equal or greater cytotoxicity in relevant preclinical models.
Purpose:
Because docetaxel has produced consistent antitumor responses in ovarian cancer patients in phase I trials, we planned and conducted a phase II clinical trial to evaluate the drug's effectiveness and its toxic effects.
Methods:
The present trial, which started in May 1992 and ended in December 1992, involved 97 patients with advanced epithelial ovarian cancer. The target study population had disease relapse or disease progression within 12 months of the last administration of a first-line or second-line platinum-based regimen with at least one bidimensionally measurable target lesion. The patients received docetaxel at a dose of 100 mg/m2 given as a 1-hour infusion every 3 weeks without premedication for minimizing potential hypersensitivity. Docetaxel-induced side effects were graded according to the National Cancer Institute's Common Toxicity Criteria.
Results:
The overall response rate was 23.6% in 76 assessable patients versus 20% if all 90 eligible patients were included in the comparison (95% confidence interval [CI] = 11%-29%). Among 34 eligible patients whose tumor progressed on the most recent platinum treatment, the response rate was 23.5% (95% CI = 8%-39%). The median progression-free survival for all eligible patients was 3.9 months, and the median overall survival was 8.4 months. Docetaxel-associated toxicity in 90 assessable patients consisted of short-lived neutropenia in 81 (90%) patients, which was complicated by fever and hospitalization in seven (8%); hypersensitivity reactions were seen in 29 (31%) patients, with significant reactions seen in seven (8%); and neurotoxicity in 43 (48%) patients, with grade 3 or above toxicity seen in only three (3%). The treatment also produced skin reactions in 58 (64%) patients, of whom only four (4%) showed the intensity of grade 3. Eleven (12%) patients experienced pleural effusions, which were the effects of the drug considered to be of greatest concern. Peripheral edema and weight gain due to fluid retention were reported in 40 (44%) and 17 (19%) patients, respectively.
Conclusion:
Docetaxel appears to be effective in the treatment of platinum-refractory ovarian cancer patients.
Insights
Docetaxel (Taxotere) shows effectiveness in treating platinum-refractory ovarian cancer, with an overall response rate of 23.6%. This study evaluated docetaxel
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Natural paclitaxel (Taxol) scarcity necessitates synthetic/semisynthetic alternatives for platinum-refractory ovarian cancer.
- Docetaxel (Taxotere), a semisynthetic taxoid, is twice as potent as paclitaxel in tubulin assembly and microtubule stabilization.
- Preclinical models indicate docetaxel's equal or greater cytotoxicity compared to paclitaxel.
Purpose of the Study:
- To evaluate the effectiveness of docetaxel in patients with advanced epithelial ovarian cancer.
- To assess the toxic effects associated with docetaxel treatment in this patient population.
Main Methods:
- A Phase II clinical trial involving 97 patients with advanced epithelial ovarian cancer (relapse/progression within 12 months of platinum-based chemotherapy).
- Docetaxel administered at 100 mg/m2 as a 1-hour infusion every 3 weeks without premedication.
- Side effects graded using the National Cancer Institute's Common Toxicity Criteria.
Main Results:
- Overall response rate was 23.6% in 76 assessable patients; 23.5% in patients progressing on platinum.
- Median progression-free survival was 3.9 months; median overall survival was 8.4 months.
- Common toxicities included neutropenia (90%), hypersensitivity reactions (31%), and neurotoxicity (48%); grade 3+ toxicities were infrequent.
Conclusions:
- Docetaxel demonstrates effectiveness in treating platinum-refractory ovarian cancer.
- The drug's toxicity profile, while notable for neutropenia and hypersensitivity, includes manageable severe adverse events.