Topotecan/Paclitaxel Active in Patients With Relapsed/Refractory Aggressive NHL

HOUSTON—There is some feeling among oncologists that treatment of relapsed/refractory non-Hodgkin’s 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 (see Table).

“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 Regimen

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.