A phase II study of high-dose celecoxib and metronomic 'low-dose' cyclophosphamide and methotrexate in patients with relapsed and refractory lymphoma.
OBJECTIVE
Relapsed, histologically aggressive non-Hodgkin lymphoma (NHL) has a poor prognosis; relapsed patients who do not respond to second line therapy or are unfit for BMT have a worse prognosis. Angiogenesis is increased in aggressive NHL and could be targeted by selective cyclooxygenase-2 inhibition and metronomic chemotherapy. We assessed the toxicity of metronomic chemotherapy and the response and progression-free survival in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).


METHODS
We prospectively studied 41 patients with a diagnosis of relapsed and/or refractory DLBCL who may have received any number of preceding therapies (as long as one included an anthracycline) and were not candidates for bone marrow transplantation. They received oral cyclophosphamide (50 mg every day), oral methotrexate (2.5 mg 4 times/week) and high-dose oral celecoxib (400 mg twice daily) until there was disease progression or unacceptable toxicity.


RESULTS
All 41 patients (median age, 56 years) were evaluable for toxicity and response, with a median follow up of 9.1 months (range, 4-35 months). At relapse, 51.2% had a high international prognostic index. The treatment protocol was well tolerated with no major toxicities. The most common toxicities were fatigue (61%), nausea (22%), neutropenia (19.5%), and anemia (22%). In 31.7% there was a partial response and 48.8% had stable disease. Progression-free survival was 12 months. The median response duration was 10 months.


CONCLUSIONS
We conclude that metronomic chemotherapy can be used for patients with relapsed and or refractory DLBCL with reasonable outcome and acceptable toxicity. Standard approaches such as hematopoietic stem cell transplantation and chemo-immunotherapy combinations should be explored prior to a decision on metronomic chemotherapy.
El Bary
Naser Abd
NA
Menoufia Faculty of Medicine, Egypt. kushia@ngha.med.sa
Hashem
Tarek
T
Metwally
Hasan
H
Ghany
Ashraf Abd
AA
El Mageed
Hager Abd
HA
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000633:toxicity; D018572:Disease-Free Survival; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000633:toxicity; D008875:Middle Aged; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage* / Q000633:toxicity; D016879:Salvage Therapy / Q000379:methods*; D013449:Sulfonamides / Q000008:administration & dosage* / Q000633:toxicity; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D003520:Cyclophosphamide; D000068579:Celecoxib; D008727:Methotrexate