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American Society of Clinical Oncology... 2013Approximately 90% of patients with early-stage Hodgkin lymphoma (HL) will be cured with first-line therapy. Chemotherapy alone or combined-modality therapy are both... (Review)
Review
Approximately 90% of patients with early-stage Hodgkin lymphoma (HL) will be cured with first-line therapy. Chemotherapy alone or combined-modality therapy are both acceptable standard treatment options for nonbulky early-stage HL. Combined-modality therapy is associated with more serious late effects and, in at least one study, showed inferior survival rates compared with chemotherapy alone. Modern radiotherapy fields and doses are likely to result in fewer complications, but given the common involvement of the mediastinum in HL, complete avoidance of the heart, lungs, and breasts in the radiotherapy field is unlikely. In patients receiving chemotherapy alone, four to six cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), with fewer cycles being given to those with an early complete remission, is recommended. Three cycles of ABVD may be adequate in those with an early negative PET, but these results have been published only in abstract form. Current standards for combined-modality therapy include two cycles of ABVD and 20 Gy of involved field radiotherapy in those with a favorable risk profile and four cycles of ABVD plus 30 Gy for unfavorable HL in early-stage patients. Standard of care for bulky early-stage HL remains combined-modality therapy. Whether an interim PET will allow selection of patients with nonbulky HL who will benefit most from consolidative radiotherapy is still under investigation.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Leukemia, Radiation-Induced; Neoplasm Staging; Neoplasms, Second Primary; Patient Selection; Positron-Emission Tomography; Prednisone; Procarbazine; Radiotherapy Dosage; Radiotherapy, Adjuvant; Risk Assessment; Treatment Outcome; Vinblastine; Vincristine
PubMed: 23714551
DOI: 10.14694/EdBook_AM.2013.33.374 -
Journal of Global Oncology Nov 2019Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with...
PURPOSE
Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with Hodgkin lymphoma (HL) relative to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. However, the associated higher cost and toxicity discourage clinicians from prescribing it. Identifying high-risk patients and administering escalated BEACOPP remains an effective strategy. We assessed the significance of interim positron emission tomography (iPET) scan after 2 cycles (iPET2) in identifying this high-risk subset.
PATIENTS AND METHODS
This cohort study used secondary data from 12 tertiary care centers in South India gathered over 10 years (2008-2018). OS, event-free survival (EFS), determinants of EFS, and complete response (CR) in iPET2 were assessed.
RESULTS
The study included 409 patients with HL (mean age, 34.5 years; male/female ratio, 1.4:1). The median duration of follow-up was 2.8 years. Of 409 patients, 63% underwent PET-based staging and 37% underwent computerized tomography (CT) staging. Stage IV (28.9%) and bone involvement (9.2%) were seen more often with PET than with CT staging (9.2% and 2%, respectively). Among 171 patients with iPET2 results, 24% did not achieve CR, and no factors were significantly associated. The 5-year EFS and OS rates of the entire cohort were 78% and 97%, respectively. The 5-year EFS and OS rates of patients with CR on iPET2 were 90% and 99%, respectively, whereas these were 65% and 100%, respectively, for patients not achieving CR. On univariable analysis, sex, stage, and iPET2 response significantly predicted inferior EFS. On multivariate analysis, only iPET2 response significantly predicted EFS ( < .000).
CONCLUSION
Our study supports the use of PET for staging and iPET2 for response assessment. Nonachievement of CR on iPET2 indicates unfavorable outcome, and such patients may benefit from more intensive treatment.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Child, Preschool; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; India; Infant; Infant, Newborn; Male; Middle Aged; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Survival Analysis; Treatment Outcome; Vinblastine; Young Adult
PubMed: 31834832
DOI: 10.1200/JGO.19.00179 -
American Journal of Hematology Sep 2020The optimal first-line treatment for advanced-stage Hodgkin's lymphoma (HL) is still a matter of debate. While ABVD is less toxic and as effective as other, more... (Clinical Trial)
Clinical Trial Comparative Study
The optimal first-line treatment for advanced-stage Hodgkin's lymphoma (HL) is still a matter of debate. While ABVD is less toxic and as effective as other, more intensive chemotherapy regimens, escalated BEACOPP (BEACOPPesc) is superior to ABVD for initial disease control and prolonged time-to-relapse. However, this advantage is associated with higher rate of early and late toxicities. As most of these data have been accumulated from clinical trials, a retrospective analysis was conducted in a large database of patients treated outside clinical trials to investigate the advantages and disadvantages of these regimes in a real-world setting. From October 2009 to October 2018, 397 advanced-stage HL patients treated with either ABVD or BEACOPPesc were retrospectively assessed in 7 European cancer centers (2 Austrian and 5 Italian centers). Complete metabolic remission (CMR) by PET was achieved in 76% and 85% of patients in the ABVD and BEACOPPesc groups, respectively (p = .01). Severe adverse events occurred more frequently with BEACOPPesc than ABVD. At a median follow-up of 8 years, 9% of the patients who achieved CMR after BEACOPPesc relapsed compared to 16.6% in the ABVD group (p = .043). No statistical difference in progression free survival (PFS) was observed between the two cohorts overall (p = .11), but there was a trend towards a superior PFS in high-risk patients treated with BEACOPPesc (p = .074). Nevertheless, overall survival was similar between the two groups (p = .94). In conclusion, we confirm that ABVD is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control, the long-term outcome remains similar between the two regimens.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Austria; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Italy; Male; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Survival Rate; Vinblastine; Vincristine
PubMed: 32419224
DOI: 10.1002/ajh.25871 -
Critical Reviews in Oncology/hematology Jun 2019Neutropenia, specifically febrile neutropenia (FN), can have profound sequelae (infection, hospitalization, mortality), and the risk of its development differs across... (Review)
Review
Neutropenia, specifically febrile neutropenia (FN), can have profound sequelae (infection, hospitalization, mortality), and the risk of its development differs across chemotherapy regimens/according to patient characteristics. We conducted a comprehensive literature review regarding neutropenia in frontline treatment of adults with advanced Hodgkin lymphoma. Guidelines state primary prophylaxis (PP) with colony-stimulating factors (CSFs) should be implemented when the risk of FN is ≥20%; CSF PP is given with standard-of-care escalated BEACOPP, but the risk of FN with standard-of-care ABVD does not necessitate routine PP. Notably, the risk of neutropenia (including FN) is higher in clinical practice versus clinical studies, and physicians overestimate their adherence to CSF guidelines. ECHELON-1 demonstrated higher FN rates with brentuximab vedotin plus AVD (A + AVD) compared with ABVD (19% vs 8%) and led to the recommendation of PP with granulocyte-CSF (G-CSF) for all A + AVD patients, highlighting the importance of readjusting our risk-assessment thinking as standard backbone regimens are modified.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Febrile Neutropenia; Female; Hodgkin Disease; Humans; Incidence; Risk Factors
PubMed: 31092364
DOI: 10.1016/j.critrevonc.2019.03.016 -
Blood Nov 2018The HD18 study for patients with newly diagnosed advanced-stage Hodgkin lymphoma (HL) used positron emission tomography (PET) after 2 cycles (PET-2) of bleomycin,...
The HD18 study for patients with newly diagnosed advanced-stage Hodgkin lymphoma (HL) used positron emission tomography (PET) after 2 cycles (PET-2) of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses (eBEACOPP) to guide further treatment. Here, we analyzed the impact of PET-2 results in the context of eBEACOPP according to the Deauville score (DS) in patients treated within the HD18 trial. Residual tissue was visually compared with reference regions according to DS. We analyzed the association between PET-2 uptake and baseline characteristics, progression-free survival (PFS), and overall survival (OS). One thousand five patients (52%) had DS1 or DS2, 471 (24%) had DS3, and 469 (24%) DS4. PET-2 uptake was associated with baseline risk factors large mediastinal mass, extranodal disease, and high International Prognostic Score ( < .0001 each). Among 722 patients receiving standard therapy with 6 cycles of eBEACOPP, 3-year PFS rates were 92.2%, 95.9%, and 87.6% with DS1-2, DS3, and DS4, respectively. Univariate hazard ratio (HR) for PFS in patients with DS4 vs DS1-3 was 2.3 (1.3-3.8; = .002). DS4 was the only factor remaining significant for PFS in a multivariate analysis including the associated baseline risk factors. Three-year OS rates were 97.6% for DS1-2, 99.0% for DS3, and 96.8% for DS4, with a univariate HR for DS4 vs DS1-3 of 2.6 (1.0-6.6; = .04). Residual uptake above that in the liver at PET-2 (ie, DS4) is an important risk factor regarding survival outcomes for patients treated with eBEACOPP upfront. We thus recommend DS4 as the cutoff value for PET-2 positivity. This trial was registered at www.clinicaltrials.gov as #NCT00515554.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Middle Aged; Positron-Emission Tomography; Prednisone; Procarbazine; Survival Analysis; Treatment Outcome; Vincristine; Young Adult
PubMed: 30166329
DOI: 10.1182/blood-2018-05-852129 -
Annals of Oncology : Official Journal... Sep 2000Evidence is recently accumulating that the novel BEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C), vincristine (O), procarbazine (P),... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Evidence is recently accumulating that the novel BEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C), vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highly effective treatment for advanced stage Hodgkin's disease. Two dose variants of BEACOPP are currently tested in a phase III randomized multicenter trial of the GHSG. To enable more extensive testing of BEACOPP we characterized its practicability regarding schedule adherence, acute hematotoxicity and need for supportive treatment.
PATIENTS AND METHODS
Data of 858 patients (6592 therapy cycles) from 184 participating institutions were evaluated. Planned total drug doses of the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480 mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1, the doses of E, A and C in the dose-intensified variant (arm 2) were escalated by factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dose reductions were specified in case of dose-limiting toxicities. Both variants are given in eight three-weekly courses.
RESULTS
Median dose adherence (dose actually given relative to planned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalation of E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians), respectively, and 70% of patients maintained elevated dose levels throughout the entire treatment. Dose-limiting toxicities occurred in 25% of cycles in arm 2, most frequently due to leukocytopenia and thrombocytopenia. Time courses of leukocytes in arm 2 showed more severe but not more prolonged leukocytopenia compared with arm 1. WHO grades 3-4 infections were documented in 2.1% (arm 1) and 3.1% (arm 2) of all cycles. Erythrocytes were transfused in 61% (arm 1) and 28% (arm 2), platelets in < 1% (arm 1) and 6% (arm 2) of all cycles.
CONCLUSIONS
Both BEACOPP schemes are practicable in a large multicenter setting. Despite increased hematotoxicity, moderate dose escalation is safe for the majority of the patients with G-CSF assistance and standard supportive treatment.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blood Platelets; Blood Transfusion; Cyclophosphamide; Disease Progression; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Leukocyte Count; Leukocytes; Leukopenia; Male; Middle Aged; Platelet Count; Prednisone; Procarbazine; Survival Analysis; Thrombocytopenia; Time Factors; Treatment Outcome; Vincristine
PubMed: 11061603
DOI: 10.1023/a:1008301225839 -
Haematologica Jan 2017Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been...
Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalated BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Bone Marrow; Combined Modality Therapy; Disease Progression; Female; Follow-Up Studies; Humans; Immunohistochemistry; Immunophenotyping; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Staging; Prognosis; Recurrence; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 27758822
DOI: 10.3324/haematol.2016.152256 -
The Lancet. Oncology Oct 2018Adverse effects on reproductive function are a key concern in young women treated with chemotherapy for advanced Hodgkin's lymphoma. We aimed to identify risk factors... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Adverse effects on reproductive function are a key concern in young women treated with chemotherapy for advanced Hodgkin's lymphoma. We aimed to identify risk factors for the extent of ovarian damage in women with Hodgkin's lymphoma treated with different chemotherapy regimens to inform accurate advice on options for fertility preservation.
METHODS
We recruited female participants from the randomised phase 3 RATHL trial, aged 18-45 years, based on availability of participants at recruiting sites in the UK. The RATHL trial key inclusion criteria were histologically confirmed classic Hodgkin's lymphoma, stage IIB-IV or IIA with adverse features (bulky disease or more than two sites of involvement), no previous treatments, and a performance status of 0-3. As part of RATHL, participants were treated with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or AVD followed by an interim PET-CT scan. Participants who had negative interim scans (PET score of 1 to 3 according to the Lugano classification) were randomly assigned (1:1) by use of minimisation, stratified by interim PET score and study centre, to continue ABVD or AVD for four more cycles. Participants with positive scans (PET score of 4 or 5) were escalated to treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP-14 or escalated BEACOPP) for four cycles. For the protocol-driven prospective cohort substudy, ovarian function was assessed before treatment, during chemotherapy, and then annually for 3 years by use of serum antimüllerian hormone and follicle-stimulating hormone measurements. The RATHL study is registered with ClinicalTrials.gov, number NCT00678327.
FINDINGS
Between Dec 13, 2010, and Dec 19, 2012, 67 eligible participants were recruited for this prospective cohort study; 57 had received ABVD or AVD (ABVD-AVD group) and ten BEACOPP-14 or escalated BEACOPP (BEACOPP group). Follow-up was fixed at 3 years. Antimüllerian hormone concentrations decreased during both chemotherapy regimens. At 1 year after chemotherapy, antimüllerian hormone concentrations recovered to a median of 10·5 pmol/L (IQR 4·3-17·3) in the ABVD-AVD group, but little recovery was seen after BEACOPP (median 0·11 pmol/L [0·07-0·20]). Age also affected the extent of ovarian function recovery, with antimüllerian hormone recovery in participants aged 35 years or older in the ABVD-AVD group to 37% (SD 10) of their before treatment concentrations, compared with full recovery to 127% (SD 12) in those younger than 35 years (p<0·0001). Follicle-stimulating hormone recovery to less than 25 IU/L occurred for 95% of women younger than 35 years in the ABVD-AVD group by 2 years and was also dependent on age (hazard ratio 0·49, 95% CI 0·37-0·65; p<0·0001).
INTERPRETATION
Reduced recovery of ovarian function observed in women older than 35 years treated with ABVD or AVD compared with younger women indicates that treatment could reduce their reproductive lifespan and supports discussion of fertility preservation before treatment. Women treated with BEACOPP should be informed of its potential high gonadotoxicity. These findings warrant further investigation in large, prospective studies with fertility and reproductive lifespan as outcomes.
FUNDING
Medical Research Foundation and Cancer Research UK.
Topics: Adolescent; Adult; Age Factors; Anti-Mullerian Hormone; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Female; Fertility Preservation; Follicle Stimulating Hormone, Human; Hodgkin Disease; Humans; Infertility, Female; Middle Aged; Neoplasm Staging; Ovary; Positron Emission Tomography Computed Tomography; Prospective Studies; Recovery of Function; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United Kingdom; Young Adult
PubMed: 30220622
DOI: 10.1016/S1470-2045(18)30500-X -
Annals of Oncology : Official Journal... Jan 2005In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly).
In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.
Topics: Administration, Oral; Aged; Aging; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Infusions, Intravenous; Prednisone; Procarbazine; Prospective Studies; Survival Analysis; Treatment Outcome; Vinblastine; Vincristine
PubMed: 15598949
DOI: 10.1093/annonc/mdi023 -
Journal of Cancer Research and Clinical... Feb 2018Although G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy...
PURPOSE
Although G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy parameters such as dosing and timing of cytotoxic drugs and G-CSF, G-CSF pharmaceuticals used and individual risk factors of patients.
METHODS
We integrate available biological knowledge and clinical data regarding cell kinetics of bone marrow granulopoiesis, the cytotoxic effects of chemotherapy and pharmacokinetics and pharmacodynamics of G-CSF applications (filgrastim or pegfilgrastim) into a comprehensive model. The model explains leukocyte time courses of more than 70 therapy scenarios comprising 10 different cytotoxic drugs. It is applied to develop optimized G-CSF schedules for a variety of clinical scenarios.
RESULTS
Clinical trial results showed validity of model predictions regarding alternative G-CSF schedules. We propose modifications of G-CSF treatment for the chemotherapies 'BEACOPP escalated' (Hodgkin's disease), 'ETC' (breast cancer), and risk-adapted schedules for 'CHOP-14' (aggressive non-Hodgkin's lymphoma in elderly patients).
CONCLUSIONS
We conclude that we established a model of human granulopoiesis under chemotherapy which allows predictions of yet untested G-CSF schedules, comparisons between them, and optimization of filgrastim and pegfilgrastim treatment. As a general rule of thumb, G-CSF treatment should not be started too early and patients could profit from filgrastim treatment continued until the end of the chemotherapy cycle.
Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Filgrastim; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoiesis; Humans; Leukopenia; Models, Biological; Neoplasms; Polyethylene Glycols; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Reproducibility of Results; Vincristine
PubMed: 29103159
DOI: 10.1007/s00432-017-2540-1