Phase II study of infusional chemotherapy with doxorubicin, vincristine and etoposide plus cyclophosphamide and prednisone (I-CHOPE) in resistant diffuse aggressive non-Hodgkin's lymphoma: CALGB 9255

Background: Patients with resistant diffuse aggressive non-Hodgkin's lymphoma (DA-NHL) have a poor prognosis. Studies have suggested infusional therapy may be beneficial. Patients and methods: This trial used an infusional regimen called I-CHOPE in resistant patients who had previously received only bolus CHOPE or CHOP regimen. Resistance was defined as: a) primary refractory disease, b) progression on therapy, c) partial response, d) complete remission lasting less than one year. Eligibility criteria included a diagnosis of DA-NHL (IWF E-H), no prior irradiation and adequate organ function. Results: Thirty-seven patients were entered and twenty-nine were eligible. Reasons for ineligibility were incorrect histology (5) and other (3). The median age was 57 years (range 29-81) with 21 males. The performance status scores were: 0 (12 patients); 1 (9 patients); 2 (8 patients). Prior therapy consisted of standard CHOP (26 patients), bolus CHOPE (2 patients), high dose CHOP (1 patient). Therapy consisted of a 120 hour continuous intravenous infusion of doxorubicin 10 mg/m(2)/day, vincristine 0.28 mg/m(2)/day (maximum 0.4 mg/day), and etoposide 48 mg/m(2)/day. Cyclophosphamide 750 mg/m(2) was given as an iv bolus day 6 and prednisone was given at 100 mg/day p.o. on days 1-5. G-CSF was allowed for myelosuppression. The overall response rate was 48% (CR 17%; PR 31%). Freedom from progression was 24% at six months and 8% at one year. Survival was 69% at six months and 40% at one year. In an exploratory analysis a prior CR or PR predicted response to I-CHOPE. Twelve of sixteen patients who had a CR/PR on previous therapy responded while two of thirteen who had no prior response, responded to I-CHOPE (P = 0.003). The toxicity was tolerable with grade 3-4 hematologic toxicity being leucopenia 94% and thrombocytopenia 41%. The grade 3-4 non-hematologic toxicities were infection in 28%, phlebitis in 11%, and stomatitis in 15%. Conclusions: I-CHOPE can induce responses in this group of patients with a poor prognosis, but most were seen in those who had previously had a response to bolus chemotherapy.