The US Food and Drug Administration (FDA) has approved a novel, shorter administration regimen for Bristol-Myers Squibbs paclitaxel(Drug information on paclitaxel) (Taxol) injection for the treatment of advanced ovarian cancer. The FDA granted approval for this new dosing regimen based on results from a multinational, phase III randomized clinical trial.
The new regimen recognizes the greater effectiveness of paclitaxel at a dose of 175 mg/m² combined with cisplatin (Platinol) at 75 mg/m² administered in a 3-hour regimen every 3 weeks, as compared to standard therapy with cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar), 750 mg/m², plus cisplatin(Drug information on cisplatin), 75 mg/m².
Paclitaxel is also approved at a dose of 135 mg/m² over a 24-hour infusion period given in combination with cisplatin (75 mg/m²) every 3 weeks. The 3-hour regimen offers patients the advantage of administration in the outpatient setting, thus avoiding hospitalization.
The results from this study confirm that Taxol in combination with cisplatin provides a significant survival benefit, compared to the previous cisplatin-plus-cyclophosphamide standard regimen, said Renzo Canetta, vice president, clinical oncology research, Bristol-Myers Squibb Pharmaceutical Research Institute. Women will now have the opportunity to receive Taxol at a higher dose in a shorter, more convenient, three-hour dosing schedule, he added.
The international trial, which was conducted by a Canadian-European consortium of cooperative groups, randomized 680 women with stage IIb through stage IV ovarian cancer. One group received paclitaxel at 175 mg/m² followed by cisplatin at 75 mg/m²in a 3-hour infusion every 3 weeks. A second group received cyclophosphamide at 750 mg/m² followed by cisplatin at 75 mg/m² over 3 hours every 3 weeks, for a median of six courses.
Women in the paclitaxel arm of the study experienced significantly improved overall survival (35.6 months), compared to women in the cyclophosphamide arm (25.9 months). Furthermore, progression-free survival was significantly higher for the women who received the paclitaxel regimen, compared to the cyclophosphamide regimen (15.3 months vs 11.5 months).
Progression-free survival remained significantly greater in the paclitaxel arm even after the investigators considered prognostic factors such as age, stage of disease, grade of disease, and residual disease.
In addition, response rates were higher in the paclitaxel arm. Notably, a large number of patients in the cyclophosphamide arm with progressive disease were subsequently treated with paclitaxel-based therapy.
Paclitaxel/Cisplatin Safety Confirmed
This pivotal study confirmed the safety of a 3-hour paclitaxel infusion with cisplatin and demonstrated that this combination resulted in a lower incidence of severe neutropenia than cyclophosphamide/cisplatin (33% vs 43%, respectively). The incidence of myalgia/arthralgia and severe neurotoxicity in the paclitaxel/cisplatin arm, however, was greater than in the cyclophosphamide/cisplatin arm (60% vs 27% and 21% vs 2%, respectively). Other side effects included anemia, nausea and vomiting, joint and muscle pain, and infection.
Severe hypersensitivity reaction, which can be fatal, can also occur with paclitaxel. All patients receiving paclitaxel should be premedicated, as described in the package insert, to help prevent this allergic reaction. Paclitaxel should not be given to patients with a history of allergic reactions to paclitaxel or other drugs formulated with Cremaphor EL (polyoxyethylated castor oil).