NEW YORKRituximab (Rituxan) used in combination with standard
chemotherapy may prolong the duration of response for patients with
B-cell non-Hodgkins lymphoma (NHL), Myron S. Czuczman, MD, said
at the Chemotherapy Foundation Symposium VII.
Dr. Czuczman, head of the Lymphoma Service at Roswell Park Cancer
Institute, reported on a phase II study of rituximab, a chimeric
anti-CD20 monoclonal antibody, used with standard CHOP chemotherapy.
Initially responsive to systemic chemotherapy, NHL nonetheless
relapses in the majority of cases, and the duration of response is
shorter with each subsequent relapse. The median survival for NHL is
6.2 years, but it falls to less than 5 years after the first relapse.
New treatments are needed because existing ones have no impact
on survival of relapsed NHL, Dr. Czuczman said.
The rationale for combining rituximab with CHOP is its demonstrated
efficacy as a single agent, the absence of cross-resistance and
overlapping toxicity with any of the CHOP components, and in vitro
data suggesting its ability to sensitize chemoresistant cell lines.
The multicenter trial enrolled 40 patients with low-grade or
follicular lymphoma, 31 newly diagnosed and 9 relapsed after prior
The patients received six cycles of standard-dose CHOP
(cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and
vincristine 1.4 mg/m² intravenously on day 1; and 100 mg/m²
oral prednisone on days 1 through 5) every 3 weeks Rituximab was
given as a 375 mg/m² infusion as follows: 7 and 2 days before
the first CHOP cycle, 2 days before the third and fifth CHOP cycle,
and two times 7 days apart following the final CHOP cycle. The
first two doses served as induction; the ones before the third and
fifth cycles were intended to utilize the synergy with the CHOP
agents; and the last two aimed to mop up any residual disease,
Dr. Czuczman explained.
Adverse events were minimal and consisted primarily of grade 1 and 2
flulike symptoms, he said, adding that the overall toxicity was
similar to that seen with CHOP alone. Grade 3 and 4 events, including
hematologic and infectious toxicities, were attributed to CHOP.
The 35 patients who completed treatment had a response rate of 95%,
with 55% (22 patients) achieving a complete response and 40% (16
patients), a partial response. Median duration of response was 39.1+
months. Median time to progression had not been reached after 40.5+
months. Dr. Czuczman said the response rate was at least equivalent
to that seen in CHOP alone. Evidence suggesting that rituximab was
also able to clear minimal residual disease, which has not been
demonstrated with CHOP alone, supports its use in this setting, he