Community-based trial of R-CHOP and maintenance rituximab for intermediate- or high-grade non-Hodgkin lymphoma with first-cycle filgrastim for older patients.

BACKGROUND: Administration of full-dose R-CHOP (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy is important to maximize response in patients with intermediate-or high-grade non-Hodgkin lymphoma but might be difficult in older patients. PATIENTS AND METHODS: This community-based study was conducted to determine response, toxicity, and disease-free survival in patients with intermediate-or high-grade non-Hodgkin lymphoma receiving R-CHOP with filgrastim. Patients received 6-8 cycles of R-CHOP followed by 4 cycles of maintenance rituximab for responders. Patients aged > 60 years or with increased infection risk received filgrastim 5 microg/kg per day in all R-CHOP cycles; other patients received filgrastim after a neutropenic event (no planned administration for cycle 1). RESULTS: Of 101 patients enrolled, 60 (59%) were aged > 60 years and received filgrastim in all cycles. Thirty-three patients aged 60 years vs. 93% 60 years vs. 95% 60 years vs. 71% 60 years vs. 78% or= 38.3 degrees C with absolute neutrophil count < 500/mm) occurred in 17% of patients overall (22% > 60 years vs. 10% 60 years vs. 2% 60 years receiving R-CHOP with filgrastim support in all cycles received comparable doses of chemotherapy and had similar overall response rates compared wtih those of younger patients receiving no preemptive cycle-1 filgrastim.

Cytoreduction of lymphoid malignancies and mobilization of blood hematopoietic progenitor cells with high doses of cyclophosphamide and etoposide plus filgrastim.

We evaluated the efficiency of high doses of cyclophosphamide (6 g/m2) and etoposide (2 g/m2) plus filgrastim (granulocyte colony-stimulating factor; G-CSF) to mobilize autologous hematopoietic progenitor cells in patients with non-Hodgkin lymphoma, multiple myeloma, and Waldenström macroglobulinemia. We also evaluated the safety of this regimen and the engraftment kinetics after myeloablative chemotherapy. Seventy-nine patients with high-risk or relapsed/primary refractory non-Hodgkin lymphoma, multiple myeloma, or Waldenström macroglobulinemia were treated. The mobilizing regimen was as follows: cyclophosphamide 600 mg/m2 twice daily for 10 doses, etoposide 200 mg/m2 twice daily for 10 doses (continuous; n=57) or 2 g/m2 over 10 hours on day 5 of etoposide (bolus; n=22), and G-CSF 5 microg/kg/d beginning day 14. Fifty-nine percent of patients achieved the primary end point (a CD34 cell dose of 5 million per kilogram with a single leukapheresis). More bolus etoposide patients achieved the primary end point (86%) compared with continuous etoposide patients (47%; P<.0001). The CD34 cell dose collected was greater in bolus etoposide patients (44 million per kilogram) than in continuous etoposide patients (10.9 million per kilogram; P<.0001). Patients took 3 weeks to recover >500/microL neutrophils and >20000/microL platelets after cyclophosphamide and etoposide. The overall response rate was 69% for non-Hodgkin lymphoma patients and 71% for multiple myeloma/Waldenström macroglobulinemia patients. The treatment-related mortality was 2.5%. Sixteen percent of surviving patients experienced grade>or=3 nonhematologic toxicity. Patients receiving bolus etoposide had significantly less grade>or=2 oral mucositis, less use of total parenteral nutrition, and less need for red blood cell and platelet transfusions. Sixty-four patients (81%) underwent autologous hematopoietic progenitor cell transplantation, with prompt engraftment. Four patients (5%) did not undergo autologous hematopoietic progenitor cell transplantation because of toxicity from high-dose cyclophosphamide and etoposide. We conclude that high doses of cyclophosphamide and etoposide combined with G-CSF are an efficient and safe mobilizing regimen for the collection of hematopoietic progenitor cells during aggressive cytoreduction of tumor burden in patients with lymphoid malignancies.

Treatment of acute leukemia with idarubicin, etoposide and cytarabine (IDEA). A randomized study of etoposide schedule.

BACKGROUND: The differences in toxicity of etoposide following continuous or bolus infusion are unknown. METHODS: We studied the schedule-dependent toxicity of high-dose etoposide when combined with high-dose cytarabine and idarubicin (IDEA) in 138 patients with acute leukemia. Four groups of patients were studied: group I, relapse; group II, secondary acute myeloid leukemia (AML); group III, de novo AML, age >60 years; and group IV, induction failure or blast crisis of myeloproliferative syndrome. Treatment for groups I-III was idarubicin 8 mg/m(2) per day days 1-3, cytarabine 2000 mg/m(2) once a day days 1-6, and etoposide 1600 mg/m(2) total dose. Group IV treatment differed by cytarabine given twice daily days 1-6. Patients were randomized to etoposide as a continuous infusion days 1-6 or as a bolus infusion over 10 h on day 7. RESULTS: Continuous infusion etoposide produced significantly more oral mucositis than bolus etoposide. In groups I-III, comparing continuous and bolus etoposide, there was a median of 3 vs 0 days of grade 2 or more oral mucositis (P<0.0001) and 13.5 vs 0 days of total parenteral nutrition (TPN) (P=0.0003). Group IV patients had a median 7 vs 0 days of grade 2 or more oral mucositis (P<0.01) and 21 vs 7 days of TPN (P<0.003), respectively. There were no differences in hematologic recovery, length of hospital stay, complete remission rate or overall survival between the two etoposide schedules. Of groups I-III patients, 51% achieved complete remission, and 11% died from treatment-related complications. CONCLUSION: The toxicity profile of high-dose etoposide is schedule-dependent with prolonged exposure producing significantly more non-hematologic toxicity.

Fourteen-day CHOP supported with granulocyte colony-stimulating factor in patients with aggressive non-Hodgkin's lymphoma: results of a phase II study.

The safety and efficacy of compressed-cycle (14-day) standard-dose CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) supported with prophylactic recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) were evaluated in patients with aggressive non-Hodgkin's lymphoma (NHL). Patients with intermediate- or high-grade NHL (Working Formulation groups D-H and J; N = 120), accrued from 25 clinical practices, were given 6 cycles of standard-dose CHOP every 14 days. Granulocyte colony-stimulating factor 5 microg/kg was given daily subcutaneously in each cycle, starting on day 2 and continuing until the absolute neutrophil count was = 10000/microL. The overall response rate was 89%, with complete responses (CRs) in 52 of 120 patients (43%) and partial responses in 55 (46%). These results are consistent with previously reported outcomes from trials in this population. Of the 720 chemotherapy cycles planned for all patients, 615 (85%) were given on time at full dose. The median relative dose intensity (RDI) of cyclophosphamide and doxorubicin was 99%; the RDI of vincristine was 73%. In the 53 patients = 60 years of age, 80% of the chemotherapy cycles were given on time at full dose, with median RDIs similar to those in the entire population. Response rates in the older patients were also similar, with CRs in 24 patients (45%) and partial responses in 21 (40%). Hematologic toxicity was significant but tolerable, with no treatment-related deaths. At a median follow-up of 20.6 months, 77% of patients were still alive. Standard-dose CHOP administered every 14 days with prophylactic G-CSF support was delivered as planned in most patients and produced response rates comparable with those with CHOP given every 3 weeks, without exceptional toxicity.