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ChemotherapyLow Dose Chemotherapy

Last update: 02/26/2013

LOW-DOSE ORAL PEP-C | About Continuous Infusion protocols



Morton Coleman, I John P. Leonard, I Courtney Lee*, I Thomas P. Kaufmann*, Michael W-Schuster.1 'Center for Lymphoma and Myeloma and Division of Hematology. Oncology, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York NY

Oral agents administered in combination on a daily basis may theoretically maintain continuous serum drug levels sufficient to override at least one mechanism of drug resistance characterized by over-expression of MDR-1.

Since 1991, 52 chemotherapy-refractory/relapsed Hodgkin's Disease and Non-Hodgkin's lymphoma patients have been treated with the PEP-C (C3) program- All patients were heavily pretreated, with 42 (81%) having received three or more prior regimens. All had prior IV bolus alkylating agents, doxorubicin, and/or etoposide.

The PEP-C regimen consisted of:

oral prednisone 20 mg each AM, 
oral cyclophosphamide 50 mg (or chlorambucil 2 mg) each afternoon, 
oral etoposide 50 mg each evening 
and oral procarbazine 50 mg at bedtime (with an oral anti-emetic). 

All medications were administered on a daily basis until the WBC was less than 3000/di, then treatment was held until recovery from nadir occurred. Therapy was then re-instituted on a daily, alternate day, or fractionated weekly basis (e.g. 5n days) depending on patient tolerance. Doses given per day were held constant. 

Thirty-three of 52 patients (63%) achieved a significant response consisting of 20 CRs (38%) and 13 PRs (25%)- Minor responses occurred in 9 (17%). Responses by histology were as follows:

follicular 12/14 (86%). 
mantle cell 6/7 (86%), 
marginal zone 5/9 (56%). 
small lymphocytic 3/6 (50%), 
Hodgkin's 3/6 (50%), diffuse large cell 3/8 (36%), and 
T cell 1/2 (50%). 

Duration of therapy ranged from 3 weeks to 32 months (median 10 months, mean 11 months), Toxicity was predominantly myelosuppression (grade 3-4: 2-1%) and minimally gastroenterologic. The PEP-C regimen is an easily administered and well tolerated oral program with significant activity in refractory/relapsed lymphoma.

Oral combination chemotherapy for refractory/relapsed lymphoma with the PEP-C (C3) regimen (daily prednisone, etoposide, procarbazine, cyclophosphamide): Low-dose continuous metronomic multidrug therapy. ASH 2007 

Responses by histology were: follicular (n=26) 92%, mantle cell (n=22) 82%, marginal zone (n=14) 71%, small lymphocytic (n=12) 67%, Hodgkin's lymphoma (n=9) 44%, diffuse large B cell (n=9) 33%, and T cell (n=5) 40%. 

Time on therapy of responding patients ranged from 3 weeks to 48 months (median 9 months, mean 11 months). Toxicity was predominantly myelosuppression, with hospitalization for infection occurring in 10 patients. Five patients developed H. zoster. Gastrointestinal effects prompting cessation of therapy occurred in 6 subjects, and 2 patients developed hematuria.


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About low dose or continuous infusion 
(metronomic dosing) of chemotherapy

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Low dose chemotherapy protocols maintain more continuous serum drug levels that may override drug resistance and possibly interfere with angiogenesis.


Palliation of relapsed aggressive histology NHL with high-dose celecoxib and 'metronomic' low-dose cyclophosphamide. - ASCO 2004
Palliation of relapsed aggressive histology NHL with high-dose celecoxib and 'metronomic' low-dose cyclophosphamide. - ASH 2004
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