Combination Chemotherapy With Nitrogen Mustard, Vincristine, Procarbazine and Prednisone in Previously Treated Patients With Hodgkin's Disease

Combination chemotherapy with fourdrugs—nitrogen mustard, vincristine,procarbazine and prednisone—was usedin 27 previously treated patients withadvanced progressive Hodgkin’s disease.Six 2-week cycles of chemotherapy wereadministered in the following schedule:nitrogen mustard, 6 mg./sq.M. I.V., andvincristine, 1.4 mg./sq.M. I.V., on days1 and 8 of each cycle; procarbazine,100 mg./sq.M. by mouth daily throughout each cycle, and prednisone, 40mg./sq.M. orally each day of cycles 1and 4. Each cycle was followed by a2-week period during which no drug wasgiven. Twenty-two patients had StageIV disease and 17 had systemic symptoms at the time of drug administration.All patients had histories of previoustherapy. Two received chemotherapyalone, 15 had radiotherapy alone and10 had both chemotherapy and radiotherapy. Nineteen out of the 27 patients(70%) had complete responses (total regression of all lesions) to the four drugcombination and five patients (19%) hadpartial responses (50% regression of alllesions). Fourteen out of the 19 whoresponded completely are still in unmaintained remission 1-24 months from therapy completion. Eighteen out of the 19who responded completely are still surviving from 6 to 30 months after thestart of combination chemotherapy.Those patients treated previously withboth radiotherapy and chemotherapy didnot respond as well as patients treatedwith prior radiotherapy alone. In general, therapy was well tolerated, withleukopenia being the major dosage-limiting toxicity. There was a progressivelypoorer tolerance to the drugs with increasing extent of prior radiotherapy.

Submitted on May 12, 1970 Revised on July 20, 1970 Accepted on July 27, 1970     

Lomustine, etoposide, vindesine, and dexamethasone (CEVD) in Hodgkin's lymphoma refractory to cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD): a multicenter trial of the German Hodgkin Study Group

Thirty-two patients with advanced Hodgkin's lymphoma resistant to cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were treated with a salvage chemotherapy regimen consisting of lomustine, etoposide, vindesine, and dexamethasone (CEVD). Twenty-seven patients were treated because of primary resistance to COPP/ABVD, and five patients were treated in early relapse (less than 12 months) after COPP/ABVD-induced complete remission. Fourteen patients (44%) achieved complete remission, and four patients achieved partial remission, with an overall response rate of 56%. Two partial responders achieved complete remission after additional radiotherapy. Four of five patients in early relapse after COPP/ABVD achieved complete remission. Consolidation radiotherapy was given for only one complete responder. Median duration of complete remission is greater than 10 months, and median survival is greater than 26 months. The treatment was well-tolerated. The main side effects were leukopenia, thrombocytopenia, mild nausea/vomiting, and cushingoid side effects. CEVD is a very active and well-tolerated salvage chemotherapy regimen in patients with Hodgkin's disease resistant to or relapsing after COPP and ABVD.     

Equitoxicity of bolus and infusional etoposide: results of a multicenter randomised trial of the German High-Grade Non-Hodgkins Lymphoma Study Group (DSHNHL) in elderly patients with refractory or relapsing aggressive non-Hodgkin lymphoma using the CEMP regimen (cisplatinum, etoposide, mitoxantrone and prednisone)

To compare toxicity of etoposide bolus with continuous infusion and to assess the efficacy of the CEMP (cisplatinum, etoposide, mitoxantrone, prednisone) regimen, 47 patients with refractory or relapsed aggressive non-Hodgkin's lymphoma older than 60 years (n=43) or not qualifying for high-dose chemotherapy (n=4) received five four-weekly CEMP cycles. Patients were randomised to start with bolus or continuous-infusion etoposide and then received bolus and infusional etoposide in an alternating fashion. The primary objective was the comparison of differences in the course of leukocytopenia and thrombocytopenia between the two application schedules. CEMP was well tolerated with little organ and moderate haematotoxicity. There was no difference in toxicity between bolus and continuous-infusion etoposide. Complete remission rate was 44% in patients relapsing >or=1 year, 27% in patients relapsing within the first year after achieving complete remission and 5% in primary refractory patients. Median event-free and overall survivals for all patients were 3 and 10 months, respectively. The observed equitoxicity and the more challenging logistics of a 60-h infusion make bolus injection the preferred application of etoposide. As the CEMP regimen is well tolerated and efficacious in elderly patients with relapsed or refractory aggressive non-Hodgkin's lymphoma for whom more aggressive therapies are not feasible, a three-weekly modification of CEMP should be tested in combination with rituximab.     

Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group

Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma (FL) when it is added to chemotherapy. In the current study, 428 patients with untreated, advanced-stage FL were randomly assigned for therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone (n = 205) or CHOP combined with rituximab (R-CHOP) (n = 223). R-CHOP reduced the relative risk for treatment failure by 60% and significantly prolonged the time to treatment failure (P < .001). In addition, a significantly higher overall response rate (96% vs 90%; P = .011) and a prolonged duration of remission (P = .001) were achieved. In spite of a relatively short observation time, these beneficial effects even translated to superior overall survival (P = .016), with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years. The predominant treatment-related adverse effect was myelosuppression. Severe granulocytopenia was more frequently observed after R-CHOP (63% vs 53%; P = .01). However, severe infections were rare and of similar frequency after R-CHOP and CHOP (5% and 7%). Hence, adding rituximab to CHOP significantly improves the outcome for patients with previously untreated advanced-stage FL and does not induce major adverse effects.