Phase II study of 'high dose' celecoxib and metronomic 'low dose' cyclophosphamide and methotrexate in patients with relapsed and refactory lymphoma

5 Aug 2009
N Abdel-Bary, T Hashem, H Metwali, A Abd el Ghany, HA Magied, M El Sherbeiny.

Introduction: Relapsed histologically aggressive non-Hodgkin's lymphoma (NHL) has a poor prognosis; relapsed patients who respond to second-line chemotherapy have a better outcome after BMT, while those who do not respond to second line or are unfit for BMT have a worse prognosis and new treatments are needed. Angiogenesis is increased in aggressive NHL and could be targeted by selective cyclooxygenase-2 inhibition and metronomic chemotherapy.

Aim of the study: Assessment of the toxicity of metronomic chemotherapy and the response and progression-free survival of relapsed diffuse large B cell lymphoma (DLCBL) patients.

Patients and methods: Forty patients with the diagnosis of relapsed and/or refractory DLCBL. Patients included in this study may have received any number of preceding therapies (as long as one had included an anthracycline) and were not candidates for BMT. They received cyclophosphamide tab (50 mg p.o. q.d), methotrexate tab (2.5 mg p.o four times per week) and high-dose celecoxib tab (400 mg p.o. b.i.d.) until disease progression or toxicity.

Results: All of the 40 patients included (median age, 56 years) were evaluable for response, 52% had a high international prognostic index at relapse, with a median follow-up of 8.4 months (range 4–23 months), 32.5% had a partial response and 50% has stable disease. Progression-free survival was 12 months. The median response duration was nine months. Treatment protocol was well tolerated with no major toxicities. The most common toxicity was fatigue (57.5%), myelo-suppression and gastrointestinal side effects.

Conclusions: Low-dose cyclophosphamide, methotrexate and high-dose celecoxib are well tolerated and active in pre-treated diffuse large cell B lymphoma. Although thrombotic events were not observed during this study, close surveillance for arterial and venous thrombotic events is recommended.

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