5-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation. Etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin)(EPOCH): Etoposide, VP-16, NSC-141540; Prednisone, PRED, NSC-10023; Vincristine, VCR, NSC-67574; Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; with Granulocyte Colony-Stimulating Factor (Amgen), Granulocyte colony-stimulating factor (G-CSF), NSC-614629.
Background: The treatment of the intermediate and aggressive non-Hodgkin's lymphomas in adults and children commonly induces complete responses in a sizable fraction of the treated population, and about 2/3 of the complete responders appear to have prolonged disease-free survival. The present study assesses the activity and tolerability in previously untreated patients of a regimen of etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin)(EPOCH) infusional chemotherapy given intensively with granulocyte colony-stimulating factor (G-CSF) support. Objectives: Primary: Assess complete response (CR) and progression-free survival (PFS) of dose-adjusted EPOCH-Rituximab (DA-EPOCH-R) with G-CSF in aggressive B-cell lymphomas. Eligibility: Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma (MGZL) and primary mediastinal B cell lymphoma (PMBL). Patients greater than or equal to 12 years old. Any Stage for PMBL and MGZL. No prior systemic chemotherapy. Human immunodeficiency virus (HIV) negative. Design: This study will estimate the complete response rate of a group of previously untreated patients and the extent to which EPOCH infusional drug delivery accompanied by a hematopoietic growth factor can increase the dose intensity of treatment. Patients receive prednisone orally for 5 days, a 96-hour infusion of vincristine, doxorubicin, and etoposide, and a bolus of cyclophosphamide on day 5. Cycles are repeated every 21 days for a total of 6-8 cycles. Patients with cluster of differentiation 20 (CD20) expressing tumors (i.e., mature B-cell lymphomas) will also receive rituximab, the humanized monoclonal antibody against the CD20 receptor on day 1 of each cycle. A total of 348 patients will be enrolled on this protocol.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
348
Etoposide 50mg/m\^2/day were delivered as continuous intravenous (CIV) infusions over 96 hours starting on day 1 every 21 days. Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.
Rituximab given on Day 1 of combination chemotherapy (EPOCH-R) every 3 weeks for 6 cycles. Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.
Prednisone 100mg by mouth (PO) twice a day (bid) on days 1 through 5 every 21 days. Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.
Cyclophosphamide 750mg/m\^2 on day 5 every 21 days. Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.
Vincristine 0.4mg/m\^2/day. Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.
Doxorubicin 10mg/m\^2/day. Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.
Baseline and/or on completion of therapy.
Baseline and/or on completion of therapy.
Baseline and/or on completion of therapy.
As clinically indicated.
As clinically indicated.
Nausea and/or vomiting.
Nausea and/or vomiting.
Gastroesophageal reflux disease (GERD).
Constipation.
Constipation
Holy Cross Hospital, Fort Lauderdale
Fort Lauderdale, Florida, United States
University of Maryland, Baltimore
Baltimore, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
St. Luke's Roosevelt Hospital
New York, New York, United States
Overall Response (Complete Response + Partial Response)
Overall response defined as a Complete Response + Partial Response was measured by the Response Criteria. Complete Response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. Partial Response is 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting for a period of at least one month.
Time frame: Time frame was from beginning of therapy until the end of therapy, an average of 6 months
Progression Free Survival (PFS)
The Dixon-Simon method will be used to determine whether large B-cell lymphomas expressing BCL-2 (+) participants may experience an improved progression free survival with Etoposide, VP-16, and Doxorubicin with Prednisone, Cyclophosphamide, and Rituximab (EPOCH-R) compared to EPOCH alone, and to obtain a concurrent, precisely determined measure of progression free survival. PFS is the time from start of treatment to documented evidence of disease progression. Progression is an increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions, or the appearance of any new lesions measured by the Response Criteria.
Time frame: Progression free survival was calculated from study entry until progression or death from any cause. Median follow up of evaluable participants was 5 years (range 2-7 years)
Proportion of Participants With Serious and/or Non-serious Adverse Events Leading to Discontinuation of Therapy
Here is the proportion of participants with adverse events leading to discontinuation of therapy. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the participant and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Initiation of study drug until 30 days after treatment, an average of 6 months
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