O R L A N D O - A d d i n g
rituximab (Rituxan) to paclitaxel
(Taxol)/topotecan (Hycamtin) salvage
therapy raises response rates by
about 25%, more than triples complete
response rates, and is effective
in both primary refractory and relapsed
aggressive B-cell lymphomas.
Phase II Study
Anas Younes, MD, and colleagues
from M.D. Anderson Cancer Center
reported data from a 45-patient phase
II study of the paclitaxel/topotecan/
rituximab regimen in a poster presentation
at the 43rd Annual Meeting
of the American Society of Hematology
"We concluded that rituximab
improves the response rate of
paclitaxel/topotecan and increases
the proportion of complete remissions.
There was not a significantly
different toxicity profile with the
addition of rituximab. However, this
is not frontline treatment yet," Dr.
Younes told ONI in an interview.
The study enrolled 45 patients
with relapsed or refractory aggressive
(NHL) and included 34 with diffuse
large cell, 4 with follicular large cell,
and 7 with transformed disease.
Twenty patients (44%) had primary
refractory disease, and 25 (56%) had
relapsed after responding to previous
therapy. Most patients had received
only a single previous regimen,
and 15 (33%) had received
prior cytarabine/platinum. The median
age was 58.
The regimen included paclitaxel
200 mg/m2 IV given over 3 hours
on day 1, topotecan 1 mg/m2 IV
given each day on days 1 to 5, and
rituximab 375 mg/m2 given 1 day
before each paclitaxel/topotecan
course. All patients also received
prophylactic filgastrim (G-CSF,
Neupogen). Courses were repeated
every 3 weeks, and patients received
a median of 31% Dr. Younes had
reported in a previous study of
paclitaxel/topotecan in a similar
group of patients.
The quality of response also improved
dramatically, with complete
responses rising from 6% with
paclitaxel/topotecan to 25% with
the three-drug regimen.
The combination had similar effects
in patients who had relapsed
after initially responding to therapy.
Adding rituximab increased the response
rate to 80% from the 65%
seen previously with paclitaxel/
topotecan, and increased the complete
response rate from 18% to 60%.
"Toxicity was comparable to what
we had seen with paclitaxel/topotecan
alone," Dr. Younes said. A total of
159 cycles of therapy were delivered.
Neutrophil counts of less than
500/μL were observed after 66 cycles
(42%), and platelets below 10,000/μL
after 16 cycles (10%). There were no
serious nonhematologic toxicities.
Febrile neutropenia occurred in 7 of
45 patients (16%).