LINKOPING, SwedenThe optimal schedule for dosing paclitaxel
(Taxol) has not been determined. However, a study that compared two
dosing schedules with the same dose intensity in ovarian cancer
patients found equivalent efficacy, with somewhat varying toxicities.
Per Rosenberg, MD, head of the Department of Gynecologic Oncology,
University Hospital, Linkoping, Sweden, presented the results at the
36th annual meeting of the American Society of Clinical Oncology.
All subjects had advanced ovarian cancer and had been treated with no
more than one regimen containing platinum. One group, with 104
evaluable subjects, started with 67 mg/m² of paclitaxel every
week. The other group, with 101 evaluable subjects, started with 200
mg/m² every 3 weeks. If no toxicity occurred, the dose was
increased. As a result, those in the weekly arm ended up with a
higher average dose intensity, but a lower total dose.
In addition, some in each group received oral steroids 6 and 12 hours
before paclitaxel, while the remaining subjects received parenteral
steroids 30 minutes before paclitaxel. Median observation time was 42
There was no significant difference in the response rate,
Dr. Rosenberg said. In the weekly paclitaxel group, 35.2% had a
complete or partial response, compared with 36.9% of the
every-third-week group. However, the researchers had to close the
study with many fewer patients than originally planned, reducing the
statistical power. So there might well be a difference in
magnitude of up to 50% without us being able to detect that, he
Also nonsignificant were the differences between survival (13.6
months in the weekly group vs 14.7 months in the every-third-week
group) and time to progression (6.1 months vs 8.1 months, respectively).
In contrast, toxicities did vary between the groups. Compared with
the weekly schedule, the every-third-week treatment caused more grade
3/4 neutropenia (45% vs 18% in the weekly group), grade 3 neuropathy
(29% vs 11%), alopecia (79% vs 46%), and joint and muscle pain (8% vs
The only toxicity seen more often in the weekly treatment group was
thickening and loosening of nails, which occurred in 9% of patients
on weekly paclitaxel and none of the patients getting it every 3
There was no difference in hypersensitivity reactions between people
getting oral steroids and those getting parenteral steroids.
We could not detect any significant difference in overall
response rate, survival, or time to progression, although this study
is underpowered, Dr. Rosenberg concluded.
A Second Study of Weekly Paclitaxel for Ovarian Cancer
Another study presented at the ASCO meeting also shows that weekly
paclitaxel (Taxol) is effective and well tolerated in treating
advanced, platinum-resistant ovarian cancer.
Maurie Markman, MD, chair of the Taussig Cancer Center at the
Cleveland Clinic Foundation, said that data from all patients who had
at least one evaluation for toxicity and response in the ongoing
trial showed a 32% response rate both in 27 patients with measurable
disease and in patients with evaluable disease based on CA-125 levels.
The study was based on observations in experimental systems that
paclitaxel cytotoxicity is highly cycle-specific. Increased
bone-marrow toxicity associated with 24-hour vs 3-hour paclitaxel
provides clinical support for the importance of cell-cycle
specificity, Dr. Markman said.
The multicenter phase II trial was designed to evaluate the toxicity
and activity of weekly paclitaxel (80 mg/m² as a 1-hour
infusion) in patients with ovarian cancer refractory both to platinum
and to paclitaxel given on a ³
The study enrolled 41 patients with ovarian cancer, primary
peritoneal carcinoma, or fallopian tube cancer. All had progression
or stable disease as best response to initial platinum/paclitaxel
therapy or recurrence within 3 months after treatment.
In 25 patients with measurable disease, there were no complete
responses but 8 partial responses (32%). In the 16 patients with
evaluable disease, 5 (32%) responded with a greater than 75% decrease
in CA-125 levels.
Weekly paclitaxel at this dose can be safely administered to
previously treated patients with ovarian cancer, with considerable
activity being observed in individuals with platinum and paclitaxel
(every-third-week schedule) resistant/refractory disease, Dr.
Markman concluded. It would be appropriate to examine a weekly
paclitaxel schedule in a randomized trial as a component of initial
chemotherapy of advanced ovarian cancer.