Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, andetoposide (CHOPE) chemotherapy for patients with diffuse lymphoma - Cancerand Leukemia Group B Studies 8852 and 8854

BACKGROUND. To address the feasibility and outcome of moderate dose intensi fication with granulocyte-colony stimulating factor (G-CSF) for patients wi th aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B ( CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, e toposide (CHOPE) regimen. METHODS. Eligibility criteria included histologically documented, diffuse s mall cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III-IV or bulky Stage II disease, and an ECOG performance status of 0-1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studi es was defined as the dose at which 50% of patients had 1) Grade 4 neutrope nia or thrombocytopenia lasting 7 days or more, or 2) Grade 3-4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100% of drug on Day 22. RESULTS. The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m(2) o n Day 1 and etoposide 100 mg/m(2) on Days 1-3 with doxorubicin 50 mg/m2 on Day 1, vincristine 1.4 mg/m(2) [maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1-5. With the addition of C-CSF at 200 mug/m(2) on Days 5-19, t he MTD was cyclophosphamide 1500 mg/m(2) and etoposide 160 mg/m2 on Days 1- 3 with standard doses of doxorubicin, vincristine, and prednisone. Increasi ng the dose of G-CSF from 200 mug/m(2) to 400 mug/m(2) did not allow for fu rther dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31% (95% confidence interval [95%Cl], 23-39) and 48% (95%Cl, 40-57), r espectively. The 5-year FFS and OS rates for eligible patients on CALGB 885 4 were 34% (95%Cl, 17-52) and 51% (95%Cl, 33-70), respectively. CONCLUSIONS. Moderate dose escalation with G-CSF is feasible. However, resp onse and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with stand ard-dose CHOP. (C) 2001 American Cancer Society.