Severe Pulmonary Toxicity in Patients With Advanced-Stage Hodgkin's Disease Treated With a Modified Bleomycin, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone, and Gemcitabine (BEACOPP) Regimen Is Probably Related to the Combination of Gemcitabine and Bleomycin: A Report of the German Hodgkin's Lymphoma Study Group

2004 ◽  
Vol 22 (12) ◽  
pp. 2424-2429 ◽  
Author(s):  
Henning Bredenfeld ◽  
Jeremy Franklin ◽  
Lucia Nogova ◽  
Andreas Josting ◽  
S. Fries ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Pulmonary Toxicity ◽  
Hodgkin’S Disease ◽  
Maximum Tolerated Dose ◽  
Multicenter Trial ◽  
Advanced Stage ◽  
Dose Escalation Study ◽  
Starting Dose ◽  
Lymphoma Study Group

Purpose To investigate a new effective, nonleukemogenic polychemotherapy regimen, BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine) in a phase I/II dose-escalation study in patients with advanced-stage Hodgkin's disease (HD). Patients and Methods Patients in clinical stages IIB with risk factors III and IV were enrolled in this nonrandomized, multicenter trial aimed at defining the maximum-tolerated dose of gemcitabine within a modified escalated BEACOPP regimen. Gemcitabine was given at a starting dose of 800 mg/m2 on days 1 and 4 of each cycle. Results Twenty-seven patients (eight female, 19 male) were enrolled with a median age of 33 years (range, 19 to 65 years). Due to a higher than expected hematotoxicity, the day-4 application of gemcitabine was omitted after 14 patients were included and 59 cycles were given. A total of eight patients developed lung toxicity, mainly pneumonitis (six of eight), which led to the termination of the study. With a median follow-up of 27 months, 25 patients are in continuing complete remission. Conclusion The substitution of etoposide by gemcitabine in the escalated BEACOPP schema is not feasible and leads to severe pulmonary toxicity. This toxicity is probably related to the concomittant application of gemcitabine and bleomycin.

Moderate Dose Escalation for Advanced Stage Hodgkin’s Disease Using the Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Scheme and Adjuvant Radiotherapy: A Study of the German Hodgkin’s Lymphoma Study Group

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4560-4567 ◽  
Author(s):  
H. Tesch ◽  
V. Diehl ◽  
B. Lathan ◽  
D. Hasenclever ◽  
M. Sieber ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Hodgkin's Disease ◽  
Residual Disease ◽  
Hodgkin’S Disease ◽  
Phase Iii ◽  
Advanced Stage ◽  
Moderate Dose ◽  
Phase Iii Study ◽  
Severe Infections ◽  
Lymphoma Study Group

Abstract The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin’s disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.

Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP.

1991 ◽  
Vol 9 (8) ◽  
pp. 1409-1420 ◽  
Author(s):  
D L Longo ◽  
P L Duffey ◽  
V T DeVita ◽  
P H Wiernik ◽  
S M Hubbard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Advanced Stage ◽  
Free Survival ◽  
Disease Free

One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival.

Moderate Dose Escalation for Advanced Stage Hodgkin’s Disease Using the Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Scheme and Adjuvant Radiotherapy: A Study of the German Hodgkin’s Lymphoma Study Group

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4560-4567 ◽  
Author(s):  
H. Tesch ◽  
V. Diehl ◽  
B. Lathan ◽  
D. Hasenclever ◽  
M. Sieber ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Hodgkin's Disease ◽  
Residual Disease ◽  
Hodgkin’S Disease ◽  
Phase Iii ◽  
Advanced Stage ◽  
Moderate Dose ◽  
Phase Iii Study ◽  
Severe Infections ◽  
Lymphoma Study Group

The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin’s disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.

Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B.

1995 ◽  
Vol 13 (8) ◽  
pp. 2005-2011 ◽  
Author(s):  
G P Canellos ◽  
G R Petroni ◽  
M Barcos ◽  
D B Duggan ◽  
B A Peterson
Keyword(s):  
Hodgkin's Disease ◽  
Pulmonary Toxicity ◽  
Overall Response Rate ◽  
Response Rate ◽  
Hodgkin’S Disease ◽  
Free Survival ◽  
Time To Treatment Failure ◽  
Group B ◽  
Leukemia Group

PURPOSE To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). PATIENTS AND METHODS Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles. Patients were restaged at 3 and 6 months. RESULTS Forty-five eligible patients were treated, with an overall response rate of 73%. There were 40% complete responses (CRs) and 33% partial responses (PRs). The median follow-up time in 42 months. The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group. Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths. Pulmonary toxicity was not observed. CONCLUSION EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy.

MOPP/EBV/CAD hybrid chemotherapy with or without limited radiotherapy in advanced or unfavorably presenting Hodgkin's disease: a report from the Italian Lymphoma Study Group.

1993 ◽  
Vol 11 (4) ◽  
pp. 712-719 ◽  
Author(s):  
P G Gobbi ◽  
C Pieresca ◽  
M Federico ◽  
N Di Renzo ◽  
F Narni ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Dose Intensity ◽  
Hematologic Toxicity ◽  
Nonhematologic Toxicity ◽  
Second Tumors ◽  
Drug Doses ◽  
Lymphoma Study Group ◽  
Length Of Therapy

PURPOSE We explored the feasibility, toxicity, and preliminary results of a chemotherapy (CT) regimen, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/epidoxirubicin, bleomycin, and vinblastine (EBV)/lomustine (CCNU), doxorubicin, and vindesine (CAD), derived through hybridization, shortening, and intensification of a corresponding 10-drug alternating combination CAD/MOPP/doxorubicin, bleomycin, and vinblastine (ABV), effective in treatment of advanced Hodgkin's disease (HD). PATIENTS AND METHODS Hybridization involved all drugs except CCNU and mechlorethamine, which were administered in alternating cycles; the length of therapy was reduced from nine to six cycles. The average projected drug doses during the six cycles were increased by 42%, with an overall 1.54 dose-intensification; epidoxorubicin was substituted for doxorubicin at equivalent tumoricidal doses. Radiotherapy (RT) was optional and its indications were limited. RESULTS Eighty assessable patients with previously untreated, advanced or unfavorably presenting HD were treated in nine cooperating institutions between 1988 and 1991. RT was delivered to 22 patients. Remissions were complete (CR) in 75 patients (93%), partial in three (4%), and null in two (3%). The median relative dose-intensity was 0.71 for the overall regimen. Three of five patients who failed to achieve CR, and two of the four who relapsed, received lower relative dose-intensive cycles. Nonhematologic toxicity was acceptable, but there was considerable hematologic toxicity. Fatal gastrointestinal bleeding was seen in one patient. CONCLUSION Caution is advised due to the short median follow-up period. Nevertheless, in addition to the excellent response rate, (1) the results were reached through abbreviation, intensification, and hybridization of an existing alternating regimen; (2) RT had limited use in this program, which may have contributed to lowering the risk of second tumors; and (3) the results were obtained in a multicenter study (a condition that often impairs results from clinical trials).

Low mortality from lymphocyte predominant hodgkin's disease with long-term follow-up

1994 ◽  
Vol 30 ◽  
pp. 268-269
Author(s):  
Stephan Bodis ◽  
Madeleine Kraus ◽  
Geraldine Pinkus ◽  
Barbara Silver ◽  
Peter Mauch
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Long Term Follow Up

Management of relapse and survival in advanced stage Hodgkin’s disease: The EORTC experience

1991 ◽  
pp. 63-66
Author(s):  
J. M. V. Burgers ◽  
R. Somers ◽  
M. Henry-Amar ◽  
M. Tarayre ◽  
P. Carde ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Advanced Stage
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