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Cancers Jul 2021Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2-3/100,000/year in the... (Review)
Review
Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2-3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. The first-line treatment for advanced stage classical HL (cHL) widely used today is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy. Randomized studies comparing these two regimens and a recently performed meta-analysis have demonstrated consistently better disease control with BEACOPP. However, this treatment is not the standard of care, as there is an excess of acute hematological toxicities and therapy-related myeloid neoplasms. Moreover, there is a recurrent controversy concerning the impact on overall survival with this regimen. More recently, new drugs such as brentuximab vedotin and checkpoint inhibitors have become available and have been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the first-line treatment of patients with advanced cHL with the objective of tumor control improvement. There are still major debates with respect to first-line treatment of advanced cHL. The use of positron emission tomography-adapted strategies has allowed a reduction in the toxicity of chemotherapy regimens. Incorporation of new drugs into the treatment algorithms requires confirmation.
PubMed: 34359646
DOI: 10.3390/cancers13153745 -
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 -
Journal of Clinical Oncology : Official... Apr 2022The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results.
METHODS
Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2- and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment.
RESULTS
In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2-/PET4-, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4- and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4- patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; = .038) had a significant lower OS than PET2-/PET4- patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively.
CONCLUSION
The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Follow-Up Studies; Hodgkin Disease; Humans; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Positron-Emission Tomography; Prednisone; Procarbazine; Vinblastine; Vincristine; Young Adult
PubMed: 34990281
DOI: 10.1200/JCO.21.01777 -
Journal of Clinical Oncology : Official... Jan 2024JCO We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of...
JCO We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of treatment de-escalation by omission of bleomycin from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for interim fluorodeoxyglucose positron emission tomography (iPET)-negative patients and assess efficacy and long-term safety for iPET-positive patients who underwent treatment intensification with escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP/BEACOPP14). The median follow-up is 7.3 years. For all patients, the 7-year progression-free survival (PFS) and overall survival (OS) are 78.2% (95% CI, 75.6 to 80.5) and 91.6% (95% CI, 89.7 to 93.2), respectively. The 1.3% difference in 3-year PFS (95% CI, -3.0 to 4.7) between ABVD and doxorubicin, vinblastine, and dacarbazine (AVD) now falls within the predefined noninferiority margin. Among 172 patients with positive iPET, the 7-year PFS was 65.9% (95% CI, 58.1 to 72.6) and the 7-year OS was 83.2% (95% CI, 76.2 to 88.3). The cumulative incidence of second malignancies at 7 years was 5.5% (95% CI, 4.0 to 7.5) for those receiving ABVD/AVD and 2.5% (95% CI, 0.8 to 7.7) for those escalated to BEACOPP. With extended follow-up, these results confirm noninferiority of treatment de-escalation after a negative iPET. Escalation with BEACOPP for iPET-positive patients is effective and safe, with no increase in second malignancies.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Follow-Up Studies; Hodgkin Disease; Neoplasms, Second Primary; Prednisone; Vinblastine; Vincristine
PubMed: 37883739
DOI: 10.1200/JCO.23.01177 -
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 -
Blood Apr 2018With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients.... (Review)
Review
With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Neoplasm Staging; Positron-Emission Tomography; Prednisone; Procarbazine; Risk Assessment; Sex Factors; Survival Rate; Vinblastine; Vincristine
PubMed: 29500174
DOI: 10.1182/blood-2017-10-772665 -
CA: a Cancer Journal For Clinicians 2004The lymphomas are a diverse group of malignant disorders that vary with respect to their molecular features, genetics, clinical presentation, treatment approaches, and... (Review)
Review
The lymphomas are a diverse group of malignant disorders that vary with respect to their molecular features, genetics, clinical presentation, treatment approaches, and outcome. Over the past few years, there have been major advances in our understanding of the biology of these diseases, leading to a universally adopted World Health Organization classification system. New therapies are now available with the potential to improve patient outcome, and the International Prognostic Index and standardized response criteria help make clinical trials interpretable. Most notably, the chimeric antiCD20 monoclonal antibody rituximab has altered our therapeutic paradigms for B-cell disorders. Combinations of this antibody with chemotherapy and other biologic agents have shown promise in treating lymphoma. Other antibodies, radioimmunoconjugates (such as Y-90 ibritumomab tiuxetan and I-131 tositumomab), and oblimerson sodium (a BCL-2 antisense oligonucleotide) have all shown promise. New chemotherapy regimens such as bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), agents such as gemcitabine, and monoclonal antibodies directed against CD30 are also being studied in Hodgkin Lymphoma. The challenge of clinical research is to optimize the use of these agents, select patients most likely to respond, and develop multitargeted strategies based on sound scientific rational, with the potential to increase the cure rate of patients with lymphomas.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Cancer Vaccines; Histone Deacetylase Inhibitors; Humans; Ki-1 Antigen; Lymphoma; Oligonucleotides, Antisense; Prognosis; Radioimmunotherapy
PubMed: 15371284
DOI: 10.3322/canjclin.54.5.260 -
Blood Feb 2007Therapy of Hodgkin disease (HD) is designed to prolong progression-free survival and minimize toxicity. The best regimen to achieve this has not yet been defined. A... (Clinical Trial)
Clinical Trial
Therapy of Hodgkin disease (HD) is designed to prolong progression-free survival and minimize toxicity. The best regimen to achieve this has not yet been defined. A total of 108 patients with newly diagnosed HD and adverse prognostic factors were prospectively studied between 1999 and 2004. They were assigned to therapy according to defined risk stratification. Patients were defined depending on the International Prognostic Score (IPS). Those with IPS of 3 or higher received 2 cycles of escalated therapy, including bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [EB]). All others received 2 cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned following 2 cycles according to results of early interim 67Ga or positron emission tomography/computed tomography (PET/CT). Following a positive interim scan, 4 cycles of EB were administered, whereas 4 cycles of SB were given to patients with a negative scan. The complete remission rate, the 5-year event-free survival (EFS), and overall survival (OS) rates were 97%, 85% and 90%, respectively. Relapse or progression occurred in 27% of patients with interim positive PET/CT versus 2.3% of negative scans (P<.02). Early interim fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT is a useful tool for adjustment of chemotherapy on an individual basis. Similar EFS and OS rates were observed for patients in both risk groups.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Monitoring; Etoposide; Female; Hodgkin Disease; Humans; Male; Middle Aged; Positron-Emission Tomography; Prednisone; Procarbazine; Prognosis; Prospective Studies; Remission Induction; Risk; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome; Vincristine
PubMed: 17018856
DOI: 10.1182/blood-2006-04-019901 -
Chinese Clinical Oncology Mar 2015Therapy for Hodgkin lymphoma (HL) is associated with excellent long-term survival rates, of 80% of more. Extended follow up has described late treatment-related... (Review)
Review
Therapy for Hodgkin lymphoma (HL) is associated with excellent long-term survival rates, of 80% of more. Extended follow up has described late treatment-related toxicities, principally secondary malignancies, cardiovascular disease and infertility. Given the young age of many patients, there is a desire to offer a more personalised approach, correlated to individual tumour biology that enables treatment de-escalation in low risk patients to reduce toxicity, and treatment intensification in high risk patients to reduce treatment failure. Contemporary therapeutic strategies have involved risk assessment based on staging and clinical factors. The use of functional imaging with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) as a predictive tool to identify early non-responders has been well validated and outperforms the risk stratifying International Prognostic Score (IPS). HL has particularly high FDG-avidity (97-100%), with FDG-PET scanning reflecting metabolic activity and acting as a surrogate biomarker for chemosensitivity. International consensus on the methods of reporting and interpreting FDG-PET scans has enabled their use to be standardised and reproducible. Given that primary therapy fails for 15-20% of patients, the use of combined FDG-PET and computerised tomography (FDG-PET/CT) to provide a response-adapted strategy to guide management is under investigation in numerous prospective clinical trials. They aim to determine whether early response scanning can be used to directly modulate subsequent therapy, through intensifying or abbreviating chemotherapy regimens and/or omitting radiotherapy. Integrated multi-modality imaging and advanced conformal planning techniques have led to the emergence of radiotherapy strategies such as involved-node radiation (INRT) that aim to optimise treatment volumes and maintain efficacy whilst lowering toxicity. Study groups have incorporated these modalities in trial designs to assess whether a PET-directed, individualised approach can become the new standard of care.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Fluorodeoxyglucose F18; Hodgkin Disease; Humans; Multimodal Imaging; Neoplasm Staging; Patient Selection; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Radiotherapy Dosage; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 25841720
DOI: 10.3978/j.issn.2304-3865.2015.03.04 -
The New England Journal of Medicine Jul 2011BEACOPP, an intensified regimen consisting of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, has been advocated as the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
BEACOPP, an intensified regimen consisting of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, has been advocated as the new standard of treatment for advanced Hodgkin's lymphoma, in place of the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
METHODS
We randomly assigned 331 patients with previously untreated and unfavorable Hodgkin's lymphoma (stage IIB, III, or IV, or an international prognostic score of ≥3 on a scale of 0 to 7, with higher scores indicating increased risk), to receive either BEACOPP or ABVD, each followed by local radiotherapy when indicated. Patients with residual or progressive disease after the initial therapy were to be treated according to a state-of-the-art high-dose salvage program. The median follow-up period was 61 months.
RESULTS
The 7-year rate of freedom from first progression was 85% among patients who had received initial treatment with BEACOPP and 73% among those who had received initial treatment with ABVD (P=0.004), and the 7-year rate of event-free survival was 78% and 71%, respectively (P=0.15). A total of 65 patients (20 in the BEACOPP group, and 45 in the ABVD group) went on to receive the intended high-dose salvage regimen. As of the cutoff date, 3 of the 20 patients in the BEACOPP group and 15 of the 45 in the ABVD group who had had progressive disease or relapse after the initial therapy were alive and free of disease. After completion of the overall planned treatment, including salvage therapy, the 7-year rate of freedom from a second progression was 88% in the BEACOPP group and 82% in the ABVD group (P=0.12), and the 7-year rate of overall survival was 89% and 84%, respectively (P=0.39). Severe adverse events occurred more frequently in the BEACOPP group than in the ABVD group.
CONCLUSIONS
Treatment with BEACOPP, as compared with ABVD, resulted in better initial tumor control, but the long-term clinical outcome did not differ significantly between the two regimens. (Funded by Fondazione Michelangelo; ClinicalTrials.gov number, NCT01251107.).
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Proportional Hazards Models; Remission Induction; Salvage Therapy; Vinblastine; Vincristine; Young Adult
PubMed: 21774708
DOI: 10.1056/NEJMoa1100340