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 THE PEP-C (C3) ORAL COMBINATION CHEMOTHERAPY REGIMEN
FOR REFRACTORY/RELAPSED LYMPHOMA: DAILY PRIEDNISONE,
ETOPOSIDE, PROCARBAZINE AND CYCLOPHOSPHAMIDE.
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.
Abstract
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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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