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Clinical & Translational Oncology :... Jun 2021Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive...
PURPOSE
Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males.
METHODS
The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels.
RESULTS
Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis.
CONCLUSIONS
ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Fertility; Hodgkin Disease; Humans; Infertility, Male; Male; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 32944834
DOI: 10.1007/s12094-020-02483-8 -
La Revue Du Praticien Mar 2017Hodgkin lymphoma affect about 1500 new patients annually in France and 60% of the patients presented a localized disease. HL is highly curable with chemotherapy such as...
Hodgkin lymphoma affect about 1500 new patients annually in France and 60% of the patients presented a localized disease. HL is highly curable with chemotherapy such as ABVD and escalated BEACOPP and for limited stage, consolidation with involved-field or involved nodes radiation therapy. Treatment could be optimized using positron emission tomography (PET) scan performed after 2 cycles to identify early responders and PET2 positive patients who are at high risk of relapse. Hodgkin lymphoma is characterized a minority of malignant Hodgkin and Reed-Sternberg (HRS) cells and a predominance of inflammatory cells. HRS cells could be targeted by antibody drug conjugates targeting CD30 showing a strong efficacy for relapsed patients. Monoclonal antibodies that are directed against the immune checkpoints especially the PD-1- PD-L1/L2 axis showed also a significant activity for patients relapsing after brentuximab vedotin and autograft. These targeted drugs are currently testing in clinical trials in early phase of the disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; France; Hodgkin Disease; Humans
PubMed: 30657300
DOI: No ID Found -
Lancet (London, England) Dec 2017The intensive polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) is... (Randomized Controlled Trial)
Randomized Controlled Trial
PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group.
BACKGROUND
The intensive polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) is very active in patients with advanced-stage Hodgkin's lymphoma, albeit at the expense of severe toxicities. Individual patients might be cured with less burdensome therapy. We investigated whether metabolic response determined by PET after two cycles of standard regimen eBEACOPP (PET-2) would allow adaption of treatment intensity, increasing it for PET-2-positive patients and reducing it for PET-2-negative patients.
METHODS
In this open-label, randomised, parallel-group phase 3 trial, we recruited patients aged 18-60 years with newly diagnosed, advanced-stage Hodgkin's lymphoma in 301 hospitals and private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. After central review of PET-2, patients were assigned (1:1) to one of two parallel treatment groups on the basis of their PET-2 result. Patients with positive PET-2 were randomised to receive six additional cycles of either standard eBEACOPP (8 × eBEACOPP in total) or eBEACOPP with rituximab (8 × R-eBEACOPP). Those with negative PET-2 were randomised between standard treatment with six additional cycles of eBEACOPP (8 × eBEACOPP) or experimental treatment with two additional cycles (4 × eBEACOPP). A protocol amendment in June, 2011, introduced a reduction of standard therapy to 6 × eBEACOPP; after this point, patients with positive PET-2 were no longer randomised and were all assigned to receive 6 × eBEACOPP and patients with negative PET-2 were randomly assigned to 6 × eBEACOPP (standard) or 4 × eBEACOPP (experimental). Randomisation was done centrally using the minimisation method including a random component, stratified according to centre, age (<45 vs ≥45 years), stage (IIB, IIIA vs IIIB, IV), international prognostic score (0-2 vs 3-7), and sex. eBEACOPP was given as previously described; rituximab was given intravenously at a dose of 375 mg/m (maximum total dose 700 mg). The primary objectives were to show superiority of the experimental treatment in the PET-2-positive cohort, and to show non-inferiority of the experimental treatment in the PET-2-negative cohort in terms of the primary endpoint, progression-free survival. We defined non-inferiority as an absolute difference of 6% in the 5-year progression-free survival estimates. Primary analyses in the PET-2-negative cohort were per protocol; all other analyses were by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00515554.
FINDINGS
Between May 14, 2008, and July 18, 2014, we recruited 2101 patients, of whom 137 were found ineligible before randomisation and a further 19 were found ineligible after randomisation. Among 434 randomised patients (217 per arm) with positive PET-2, 5-year progression-free survival was 89·7% (95% CI 85·4-94·0) with eBEACOPP and 88·1% (83·5-92·7) with R-eBEACOPP (log-rank p=0·46). Patients with negative PET-2 randomly assigned to either 8 × eBEACOPP or 6 × eBEACOPP (n=504) or 4 × eBEACOPP (n=501) had 5-year progression-free survival of 90·8% (95% CI 87·9-93·7) and 92·2% (89·4-95·0), respectively (difference 1·4%, 95% CI -2·7 to 5·4). 4 × eBEACOPP was associated with fewer severe infections (40 [8%] of 498 vs 75 [15%] of 502) and organ toxicities (38 [8%] of 498 vs 91 [18%] of 502) than were 8 × eBEACOPP or 6 × eBEACOPP in PET-2-negative patients. Ten treatment-related deaths occurred: four in the PET-2-positive cohort (one [<1%] in the 8 × eBEACOPP group, three [1%] in the 8 × R-eBEACOPP group) and six in the PET-2-negative group (six [1%] in the 8 × eBEACOPP or 6 × eBEACOPP group).
INTERPRETATION
The favourable outcome of patients treated with eBEACOPP could not be improved by adding rituximab after positive PET-2. PET-2 negativity allows reduction to only four cycles of eBEACOPP without loss of tumour control. PET-2-guided eBEACOPP provides outstanding efficacy for all patients and increases overall survival by reducing treatment-related risks for patients with negative PET-2. We recommend this PET-2-guided treatment strategy for patients with advanced-stage Hodgkin's lymphoma.
FUNDING
Deutsche Krebshilfe, Swiss State Secretariat for Education and Research, and Roche Pharma AG.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Austria; Bleomycin; Cyclophosphamide; Czech Republic; Doxorubicin; Etoposide; Female; Germany; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasm Staging; Netherlands; Positron-Emission Tomography; Prednisone; Procarbazine; Rituximab; Switzerland; Treatment Outcome; Vincristine; Young Adult
PubMed: 29061295
DOI: 10.1016/S0140-6736(17)32134-7 -
The Lancet. Oncology Apr 2017Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during... (Randomized Controlled Trial)
Randomized Controlled Trial
Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPP alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group.
BACKGROUND
Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPP) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy.
METHODS
In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPP and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPP chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPP (BEACOPP group) or BEACOPP plus rituximab (R-BEACOPP group). PET-2 was assessed using a 5-point scale with FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPP was given as previously described; rituximab was given intravenously at a dose of 375 mg/m (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPP (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component, stratified according to centre, age, stage, international prognostic score, and sex. The primary efficacy endpoint was 5 year progression-free survival, analysed in the intention-to-treat population. We are reporting this second planned interim analysis as the final report of the trial. The trial is registered with ClinicalTrials.gov, number NCT00515554.
FINDINGS
Between May 14, 2008, and May 31, 2011, we enrolled 1100 patients. 440 patients had a positive PET-2 and were randomly assigned to either the BEACOPP group (n=220) or the R-BEACOPP group (n=220). With a median follow-up of 33 months (IQR 25-42) for progression-free survival, estimated 3 year progression-free survival was 91·4% (95% CI 87·0-95·7) for patients in the BEACOPP group and 93·0% (89·4-96·6) for those in the R-BEACOPP group (difference 1·6%, 95% CI -4·0 to 7·3; log rank p=0·99). Common grade 3-4 adverse events were leucopenia (207 [95%] of 218 patients in the BEACOPP group vs 211 [96%] of 220 patients in the R-BEACOPP group), and severe infections (51 [23%] vs 43 [20%] patients). Based on a futility analysis, the independent data monitoring committee recommended publication of this second planned interim analysis as the final result. Six (3%) of 219 patients in the BEACOPP group and ten (5%) of 220 in the R-BEACOPP group died; fatal treatment-related toxic effects occurred in one (<1%) patient in the BEACOPP group and three (1%) in the R-BEACOPP group, all of them due to infection.
INTERPRETATION
The addition of rituximab to BEACOPP did not improve the progression-free survival of PET-2 positive patients with advanced stage Hodgkin's lymphoma. However, progression-free survival for PET-2 positive patients was much better than expected, exceeding even the outcome of PET-2-unselected patients in the previous HD15 trial. Thus, PET-2 cannot identify patients at high-risk for treatment failure in the context of the very effective German Hodgkin Study Group standard treatment for advanced stage Hodgkin's lymphoma.
FUNDING
Deutsche Krebshilfe; Swiss State Secretariat for Education, Research and Innovation (SERI); and Roche Pharma.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; International Agencies; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Positron-Emission Tomography; Prednisone; Procarbazine; Prognosis; Rituximab; Survival Rate; Vincristine
PubMed: 28236583
DOI: 10.1016/S1470-2045(17)30103-1 -
Clinical Lymphoma & Myeloma Dec 2007ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) and BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) are the most... (Review)
Review
ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) and BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) are the most widely used regimens for the treatment of patients with advanced stage Hodgkin lymphoma. Both regimens are associated with significant neutropenia. Maintaining the planned dose intensity is considered an important goal to achieve when using curative therapy. Therefore, prophylactic use of granulocyte colony-stimulating factor (G-CSF) is widely used to support these regimens and is mandatory to support BEACOPP-escalated and BEACOPP-14 to reduce toxicity and treatment delays. Recent retrospective studies are discussed which have reported using ABVD without G-CSF support. However, randomized studies are needed to clarify the role of primary prophylaxis with ABVD and BEACOPP-baseline regimens. Secondary prophylaxis should be considered in all patients, especially those who develop neutropenic fever.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Filgrastim; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Prednisone; Procarbazine; Recombinant Proteins; Vinblastine; Vincristine
PubMed: 18284718
DOI: 10.3816/clm.2007.s.035 -
Internal Medicine Journal Jun 2018
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Osteonecrosis; Prednisone; Procarbazine; Treatment Outcome; Vincristine
PubMed: 29898275
DOI: 10.1111/imj.13813 -
BMJ Clinical Evidence Jun 2009People with Hodgkin's lymphoma usually present with a lump in the neck or upper chest, but a quarter of people also have fever, sweating, weight loss, fatigue, and itch.... (Review)
Review
INTRODUCTION
People with Hodgkin's lymphoma usually present with a lump in the neck or upper chest, but a quarter of people also have fever, sweating, weight loss, fatigue, and itch. Almost all people with localised disease can be cured, and, even among people with relapsed advanced disease, almost 80% survive event free for 4 years or more.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: single-regimen chemotherapy treatments; combined chemotherapy and radiotherapy treatments compared with radiotherapy alone; and combined chemotherapy and radiotherapy treatments compared with the same chemotherapy agent alone, for first presentation stage I or II non-bulky disease? What are the effects of: specific combined chemotherapy and radiotherapy treatments versus each other; or different radiotherapy treatment strategies in stage I or II non-bulky disease? What are the effects of: single-regimen chemotherapy treatments; dose-intensified chemotherapy treatments; or combined chemotherapy plus radiotherapy treatments compared with chemotherapy alone, for first presentation stage II (bulky) disease, III, or IV disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: ABVD (with or without radiotherapy); ABVPP plus radiotherapy; ChlVPP-EVA; COPP-ABVD plus radiotherapy; CVPP plus radiotherapy; EBVP plus radiotherapy; escalating-dose BEACOPP; extended-field radiotherapy; increased-dose regimens; involved-field radiotherapy; MOPP (with or without radiotherapy); MOPP-ABV plus radiotherapy; and VBM plus radiotherapy.
Topics: Etoposide; Hodgkin Disease; Humans
PubMed: 21726488
DOI: No ID Found -
Leukemia & Lymphoma Sep 2006A German Hodgkin's lymphoma (HL) study group designed the BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) regimen.... (Comparative Study)
Comparative Study
A German Hodgkin's lymphoma (HL) study group designed the BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) regimen. In the BEACOPP regimen, treatment intervals were shortened and the dose-intensity was increased compared with those in the ABVD regimen (doxorubicin, bleomycin, vinblastine and darcarbacine), resulting in a long-term disease-free survival rate of approximately 75-80%. In the present study, we evaluated the safety and efficacy of the BEACOPP regimen. Between April 2001 and February 2004, 20 patients with HL of stage IIB or higher who had received no previous treatment were enrolled. The patients were aged 17-69 years (median 22 years). The histologic types were mixed cellularity in four cases and nodular sclerosis in 16 cases. The stages were stage IIB in four cases, stage III in 12 cases, and stage IV in four cases. Nineteen (95%) of the 20 patients achieved complete remission. The 3-year survival rate was 100% and the 3-year progression-free survival rate was 89.7%. Adverse drug reactions were grade 4 neutropenia in 12 patients, grade 3-4 thrombocytopenia in seven patients, and grade 3 or higher non-hematologic toxicities in two patients (stomatitis in one patient and ALT/AST elevation in one patient). The BEACOPP regimen for advanced-stage HL showed an excellent complete remission rate and high efficacy even in stage III/IV patients. However, a long-term risk of the BEACOPP regimen is the development of secondary leukemia or myelodysplastic syndrome. Therefore, long-term follow-up of these patients, including monitoring for toxicities, is necessary.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Treatment Outcome; Vinblastine; Vincristine
PubMed: 17065005
DOI: 10.1080/10428190600688313 -
Journal of Clinical Oncology : Official... Oct 2016
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Procarbazine; Vinblastine; Vincristine
PubMed: 27528721
DOI: 10.1200/JCO.2016.67.9431 -
Journal of Clinical Oncology : Official... Nov 2011Eight cycles of BEACOPP(escalated) (escalated dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by... (Comparative Study)
Comparative Study Randomized Controlled Trial
Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group.
PURPOSE
Eight cycles of BEACOPP(escalated) (escalated dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by radiotherapy (RT) to initial bulk or residual tumor mass is the German Hodgkin Study Group standard of care for advanced-stage Hodgkin's lymphoma (HL). However, treatment-related toxicity is a concern, and the role of RT in this setting is unclear. The HD12 study thus aimed to reduce toxicity while maintaining efficacy.
PATIENTS AND METHODS
In this prospectively randomized multicenter trial, eight cycles of BEACOPP(escalated) was compared with four cycles of BEACOPP(escalated) followed by four cycles of the baseline dose of BEACOPP (BEACOPP(baseline); 4 + 4), and RT with no RT in the case of initial bulk or residual disease. The study was designed to exclude a difference in 5-year freedom from treatment failure (FFTF) rate of 6%.
RESULTS
Between January 1999 and January 2003, 1,670 patients age 16 to 65 years were enrolled onto the HD12 study. At 5 years, FFTF was 86.4% in the BEACOPP(escalated) arm and 84.8% in the 4 + 4 arm (difference, -1.6%; 95% CI, -5.2% to 1.9%), and overall survival was 92% versus 90.3% (difference, -1.7%; 95% CI, -4.6% to 1.1%). Deaths related to acute toxicity of chemotherapy were observed in 2.9% of patients (BEACOPP(escalated), n = 19; 4 + 4, n = 27). FFTF was inferior without RT (90.4% v 87%; difference, -3.4%; 95% CI, -6.6% to -0.1%), particularly in patients who had residual disease after chemotherapy (difference, -5.8%; 95% CI, -10.7% to -1.0%), but not in patients with bulk in complete response after chemotherapy (difference, -1.1%; 95% CI, -6.2% to 4%).
CONCLUSION
The reduction of BEACOPP to the 4 + 4 regimen did not substantially reduce severe toxicity but might decrease efficacy. Our results do not support the omission of consolidation RT for patients with residual disease. Alternative strategies for improving the risk-to-benefit ratio for patients with advanced HL are needed.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemoradiotherapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Middle Aged; Prednisone; Procarbazine; Treatment Failure; Vincristine
PubMed: 21990399
DOI: 10.1200/JCO.2010.33.9549