HOUSTONThere is some feeling among oncologists that
treatment of relapsed/refractory non-Hodgkins lymphoma (NHL)
with CHOP (cyclophosphamide, doxorubicin, vincristine, and
prednisone) may have gone about as far as it can go. Variations on
standard CHOP have produced little improvement, and new approaches
are clearly needed.
Anas Younes, MD, and colleagues at M.D. Anderson Cancer Center
reported at the ASH meeting that a combination of paclitaxel (Taxol)
and topotecan (Hycamtin) with G-CSF (Neupogen) support looks promising.
Dr. Younes provided interim data from a phase II study of the new
combination and compared those results with previous M.D. Anderson
studies with each drug alone and with paclitaxel/cyclophosphamide
With CHOP, we can cure only 50% of patients, and this 50% cure
rate has not changed in the past three decades, Dr. Younes
said. Many trials in the past added one, two, or three drugs to
CHOP. We have to come up with radical new combinations. That is why
we are interested in paclitaxel/topotecan-based programs.
Patients were eligible for the study if they had relapsed or
refractory NHL of the following histologies: diffuse large B-cell
lymphoma, peripheral T-cell lymphoma, follicular center-cell grade
III lymphoma, or anaplastic large-cell lymphoma. No more than two
prior treatment regimens were allowed.
Treatment consisted of paclitaxel, 200 mg/m² infused IV over 3
hours on day 1, with concurrent topotecan, 1 mg/m² infused IV
over 30 minutes on days 1 through 5. All patients received G-CSF
prophylactically until their neutrophil count reached 3,000/mm³.
Courses were repeated every 3 weeks.
After three courses, objective tumor response was assessed, and
responding patients were allowed to receive consolidation with
high-dose therapy/stem cell transplant if eligible, or to continue
for a maximum of six courses.
Thirty-eight patients were registered for the trial, and 33 were
evaluable. The median number of prior regimens was two, and 10
patients (30%) had received a prior cytarabine/platinum-containing regimen.
Dr. Younes reported that the paclitaxel/topotecan regimen produced an
overall response rate of 27% in 15 patients with primary refractory
disease, including two partial remissions and two complete
remissions. The combination produced an overall response rate of 72%
in 18 patients with relapsed disease, including 12 partial remissions
and one complete remission.
PRs Allowed to Cross Over
We had more partial remissions than complete remissions because
of the design of the trial, he explained. Patients who
achieved at least a partial remission after three courses of
treatment were allowed to cross over and receive high-dose
chemotherapy/transplant, so many patients did not receive the full
six courses of chemotherapy.
Treatment was well tolerated with no major life threatening
toxicities, Dr. Younes said.
We are testing this combination in the salvage setting, hoping
to be able to move it up front for patients who are unlikely to
respond to CHOP, based on a prognostic factor model, he said.