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Annals of Oncology : Official Journal... 1998The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial Review
The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Disease Progression; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Middle Aged; Prednisone; Procarbazine; Survival Rate; Treatment Outcome; Vinblastine; Vincristine
PubMed: 9926240
DOI: 10.1093/annonc/9.suppl_5.s67 -
American Family Physician Jan 2020Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma.... (Review)
Review
Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma. Approximately 82,000 new U.S. patients are diagnosed with lymphoma annually. Any tobacco use and obesity are major modifiable risk factors, with genetic, infectious, and inflammatory etiologies also contributing. Lymphoma typically presents as painless adenopathy, with systemic symptoms of fever, unexplained weight loss, and night sweats occurring in more advanced stages of the disease. An open lymph node biopsy is preferred for diagnosis. The Lugano classification system incorporates symptoms and the extent of the disease as shown on positron emission tomography/computed tomography to stage lymphoma, which is then used to determine treatment. Chemotherapy treatment plans differ between the main subtypes of lymphoma. Non-Hodgkin lymphoma is treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (R-CHOP), bendamustine, and lenalidomide. Hodgkin lymphoma is treated with combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), Stanford V (a chemotherapy regimen consisting of mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone), or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with radiotherapy. Subsequent chemotherapy toxicities include neuropathy, cardiotoxicity, and secondary cancers such as lung and breast, and should be considered in the shared decision-making process to select a treatment regimen. Once remission is achieved, patients need routine surveillance to monitor for complications and relapse, in addition to age-appropriate screenings recommended by the U.S. Preventive Services Task Force. Patients should receive a 13-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide vaccine at least eight weeks later with additional age-appropriate vaccinations because lymphoma is an immunosuppressive condition. Household contacts should also be current with their immunizations.
Topics: Adult; Aged; Antineoplastic Agents; Biopsy; Evidence-Based Medicine; Female; Humans; Lymphoma; Male; Middle Aged; Neoplasm Staging; Risk Factors; United States
PubMed: 31894937
DOI: No ID Found -
Clinical Lymphoma Jun 2005
Comparative Study Review
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Prednisone; Procarbazine; Survival Analysis; Vinblastine; Vincristine
PubMed: 15989708
DOI: 10.3816/clm.2005.n.028 -
Journal of Clinical Oncology : Official... Jun 2017Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron... (Randomized Controlled Trial)
Randomized Controlled Trial
Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated-according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)-stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET-361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemoradiotherapy; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasm Staging; Positron-Emission Tomography; Prednisone; Procarbazine; Survival Rate; Vinblastine; Vincristine; Young Adult
PubMed: 28291393
DOI: 10.1200/JCO.2016.68.6394 -
Annals of Oncology : Official Journal... 1998In this article we summarize the theoretical arguments which led us in the German Hodgkin's Disease Study Group to introduce the BEACOPP-regimen and to initiate a large... (Review)
Review
In this article we summarize the theoretical arguments which led us in the German Hodgkin's Disease Study Group to introduce the BEACOPP-regimen and to initiate a large randomised trial to investigate the role of moderate dose escalation in the treatment of advanced stage Hodgkin's disease. Although some indications for a role of dose were available in the early 1990s no prospective randomised trial had been undertaken. In order to obtain an impression of the shape of the essential dose response characteristic we developed a novel statistical model that could be used to analyse a set of data in which dose variations had occurred. The model took tumour growth and chemotherapy effects into account. The model could be applied to clinical data on tumour control and treatment given in a patient population. The model was fitted to the data of 706 patients which had received COPP/ABVD-like regimens. It revealed considerable heterogeneity in chemosensitivity and a positive slope of the doseresponse relationship. The model was used to simulate the effect of various treatment strategies with dose escalation and schedule changes. On the basis of such simulations we predicted that shortening cycle intervals from 4 to 3 weeks should lead to small benefits (about 3% in five-year tumour control rates). In contrast, we predicted that a moderate average dose escalation by 30% of a standard chemotherapy would lead to a potential benefit in the order of 10%-15% in tumour control at five years. Subsequently we searched for a treatment scheme that would permit such a dose escalation. The BEACOPP-scheme was invented to allow the three major myelotoxic substances (cyclophsphamide, adriamycin and etoposide) to be given in the beginning of a cycle. These three substances were then subject to dose escalation in a dose finding trial. G-CSF was introduced to compensate for the myelotoxic effects. The dose level found feasible for a large multicentre setting turned out to be in the required magnitude. The HD9 trial of the GHSG was then initiated to examine whether the predicted dose response curve really exists.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Division; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Forecasting; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Kinetics; Models, Theoretical; Prednisone; Procarbazine; Research Design; Treatment Outcome; Vincristine
PubMed: 9926241
DOI: 10.1093/annonc/9.suppl_5.s73 -
Journal of Clinical Oncology : Official... Apr 2016
Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Hodgkin Disease; Humans; Male
PubMed: 26712223
DOI: 10.1200/JCO.2015.64.8683 -
Current Hematologic Malignancy Reports Jul 2007The majority of patients with advanced Hodgkin's lymphoma are cured with currently available therapy, such as ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, and... (Comparative Study)
Comparative Study Review
The majority of patients with advanced Hodgkin's lymphoma are cured with currently available therapy, such as ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine). However, almost 20% of patients fail to achieve a complete remission and almost 40% relapse with prolonged follow-up. BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) was developed by the German Hodgkin's Study Group to improve on standard therapy by intensifying treatment and substituting the active agent etoposide for vinblastine and dacarbazine. Promising results led to the HD9 trial, in which escalated BEACOPP was superior to COPP/ABVD (cyclophosphamide, vincristine, prednisone, procarbazine/ABVD). Nevertheless, escalated BEACOPP is myelosuppressive and is associated with an increased risk of secondary malignancies. Modifications of BEACOPP have been developed in an attempt to increase efficacy and reduce the adverse effects. Whether BEACOPP should be selected in preference to ABVD may be determined by clinical stage, patient age, and other risk factors. The answer to whether escalated BEACOPP is superior to ABVD will require the results of an ongoing randomized trial.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Female; Forecasting; Hodgkin Disease; Humans; Infertility; Male; Multicenter Studies as Topic; Neoplasms, Second Primary; Patient Selection; Prednisone; Procarbazine; Remission Induction; Survival Rate; Treatment Outcome; Vinblastine; Vincristine
PubMed: 20425365
DOI: 10.1007/s11899-007-0022-2 -
Annals of Oncology : Official Journal... Feb 1997At present, treatment results for patients with advanced-stage Hodgkin's disease remain unsatisfactory. Standard chemotherapy M(C)OPP (nitrogen mustard...
PURPOSE
At present, treatment results for patients with advanced-stage Hodgkin's disease remain unsatisfactory. Standard chemotherapy M(C)OPP (nitrogen mustard (cyclophosphamide). vincristine, procabazine, and prednisone). ABVD (adriamycine, bleomycine, vinblastine, and dacarbacine) or M(C)OPP/ABVD +/- radiotherapy fail to achieve long-term complete remission in 35% to 50% of these patients. The BEACOPP (bleomycin, etoposide, adriamycine, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen was developed to improve treatment results by dose intensification achieved by reduced duration of treatment (time intensification) and addition of etoposide.
PATIENTS AND METHODS
Thirty untreated patients with advanced Hodgkin's disease stage IIB IV according to the Ann Arbor classification were treated with the time intensified BEACOPP regimen. Each patient was scheduled to receive eight cycles of chemotherapy with consolidating radiotherapy to sites of initial bulk disease and to residual tumor remaining after chemotherapy.
RESULTS
All patients were evaluable for assessment of toxicity, treatment response, freedom from treatment failure (FFTF) and survival (SV). Of 30 treated patients, 29 patients received the intended eight cycles of BEACOPP. One patient in clinical CR, terminated the chemotherapy at his own request after six cycles and is at this time, 48 months after the end of treatment, in complete remission. Toxicity was tolerable with WHO grade 3/4 leucopenia in 28% of chemotherapy cycles and one severe (WHO grade 3) infection. No treatment-related death occurred. Cycles could generally be given on schedule. Complete remission (CR) was achieved in all but two patients (93%). At present, only one patient has relapsed. At a median follow-up of 40 months, FFTF-rate is 89% (lower confidence limit: 80%). One patient died due to progressive disease.
CONCLUSION
The BEACOPP regimen is feasible at moderate hematopoeitic toxicity. With a FFTF-rate of 89% at a median follow-up of 40 months, the treatment results are very encouraging. A prospective randomised trial has been initiated to compare the BEACOPP regimen with the standard COPP/ABVD regimen in advanced-stage Hodgkin's disease.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Middle Aged; Pilot Projects; Prednisone; Procarbazine; Treatment Outcome; Vincristine
PubMed: 9093722
DOI: 10.1023/a:1008294312741 -
Annals of Oncology : Official Journal... Oct 2003Hodgkin's disease (HD) is the most common non-AIDS-defining tumor diagnosed in HIV-infected patients. Antineoplastic treatment is difficult considering the underlying... (Clinical Trial)
Clinical Trial
BACKGROUND
Hodgkin's disease (HD) is the most common non-AIDS-defining tumor diagnosed in HIV-infected patients. Antineoplastic treatment is difficult considering the underlying immunodeficiency caused by HIV itself and may increase the risk of opportunistic infections. The purpose of this study was to evaluate the efficacy and safety of the chemotherapeutic regimen bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in HIV-infected patients with HD (HIV-HD).
PATIENTS AND METHODS
Twelve patients with HIV-HD were scheduled to receive six cycles of BEACOPP. Five patients received concomitant antiretroviral therapy. Two patients received additional radiotherapy. Restaging was carried out after three and six cycles of chemotherapy. CD4 counts and HIV RNA levels were regularly monitored during the course of chemotherapy.
RESULTS
Complete remission (CR) was achieved in all patients. Of 12 patients, eight patients received the intended six cycles of BEACOPP. Two patients died of opportunistic infections within the treatment period, one patient died of a relapse after 26 months. The other nine patients remain in CR for their individual follow-up period, median 49 months (range 13-108). The most commonly observed toxicity was bone marrow suppression with National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 leukopenia in 75% of all cases. The mean decline of CD4+ lymphocytes was 238 +/- 230/ micro l, with a mean recovery of 272 +/- 329/ micro l 6 months after the last cycle. Plasma levels of HIV RNA increased moderately or even declined under chemotherapy if highly active anti-retroviral therapy was given concomitantly with BEACOPP.
CONCLUSIONS
The BEACOPP regimen is feasible and highly effective in HIV-HD patients. With respect to its overall moderate toxicity, BEACOPP is a safe regimen even in the immunocompromised patient.
Topics: AIDS-Related Opportunistic Infections; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; CD4 Lymphocyte Count; Cyclophosphamide; Doxorubicin; Etoposide; Female; HIV Infections; Hodgkin Disease; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; RNA; Treatment Outcome; Vincristine
PubMed: 14504059
DOI: 10.1093/annonc/mdg408 -
The New England Journal of Medicine Jun 2016We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma.
METHODS
Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points.
RESULTS
A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%.
CONCLUSIONS
Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Disease-Free Survival; Doxorubicin; Female; Hodgkin Disease; Humans; Male; Middle Aged; Positron-Emission Tomography; Prospective Studies; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome; Vinblastine; Young Adult
PubMed: 27332902
DOI: 10.1056/NEJMoa1510093