The US Food and Drug Administration (FDA) has approved a novel,
shorter administration regimen for Bristol-Myers Squibbs
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 (Cytoxan, Neosar),
750 mg/m², plus 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
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).