Early chemotherapy intensification with escalated beacopp in patients with advanced-stage hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two abvd cycles: Long-term results of the GITIL/FIL HD 0607 trial

A. Gallamini, C. Tarella, S. Viviani, A. Rossi, C. Patti, A. Mule, M. Picardi, A. Romano, M. Cantonetti, G.L. Nasa, L. Trentin, S. Bolis, D. Rapezzi, R. Battistini, D. Gottardi, P. Gavarotti, P. Corradini, M. Cimminiello, C. Schiavotto, G. ParvisR. Zanotti, G. Gini, A.J.M. Ferreri, P. Viero, M. Miglino, A. Billio, A. Avigdor, A. Biggi, F. Fallanca, U. Ficola, M. Gregianin, A. Chiaravalloti, G. Prosperini, F. Bergesio, S. Chauvie, C. Pavoni, A.M. Gianni, A. Rambaldi

Research output: Contribution to journalArticle

Abstract

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≤ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively (P > .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% (P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL. © 2018 by American Society of Clinical Oncology.
Original languageEnglish
Pages (from-to)454-462
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number5
DOIs
Publication statusPublished - 2018

Fingerprint

Hodgkin Disease
Drug Therapy
Disease-Free Survival
Vincristine
Doxorubicin
Positron Emission Tomography Computed Tomography
Radiotherapy
Procarbazine
Dacarbazine
Vinblastine
Bleomycin
Etoposide
Prednisone
Positron-Emission Tomography
Cyclophosphamide
Survival

Keywords

  • alanine aminotransferase
  • antineoplastic agent
  • aspartate aminotransferase
  • bleomycin
  • cyclophosphamide
  • dacarbazine
  • doxorubicin
  • etoposide
  • fluorodeoxyglucose f 18
  • prednisone
  • procarbazine
  • rituximab
  • vinblastine
  • vincristine
  • add on therapy
  • adolescent
  • adult
  • advanced cancer
  • alanine aminotransferase blood level
  • Article
  • aspartate aminotransferase blood level
  • blood clotting disorder
  • blood toxicity
  • bone marrow toxicity
  • cancer combination chemotherapy
  • cancer growth
  • cancer mortality
  • cancer patient
  • cancer radiotherapy
  • cancer regression
  • cancer survival
  • classical Hodgkin lymphoma
  • controlled study
  • drug dose escalation
  • drug dose intensification
  • drug hypersensitivity
  • drug substitution
  • drug treatment failure
  • drug withdrawal
  • early intervention
  • event free survival
  • female
  • gastrointestinal infection
  • heart failure
  • hepatobiliary disease
  • human
  • long term survival
  • lung fibrosis
  • lung infection
  • lung toxicity
  • male
  • metabolic disorder
  • multiple cycle treatment
  • musculoskeletal disease
  • nausea and vomiting
  • neurotoxicity
  • neutropenia
  • open study
  • overall survival
  • pain
  • pancreas disease
  • phase 2 clinical trial
  • positron emission tomography-computed tomography
  • priority journal
  • progression free survival
  • randomized controlled trial
  • side effect
  • skin toxicity
  • soft tissue disease
  • treatment response
  • vascular disease
  • young adult

Cite this

Early chemotherapy intensification with escalated beacopp in patients with advanced-stage hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two abvd cycles: Long-term results of the GITIL/FIL HD 0607 trial. / Gallamini, A.; Tarella, C.; Viviani, S.; Rossi, A.; Patti, C.; Mule, A.; Picardi, M.; Romano, A.; Cantonetti, M.; Nasa, G.L.; Trentin, L.; Bolis, S.; Rapezzi, D.; Battistini, R.; Gottardi, D.; Gavarotti, P.; Corradini, P.; Cimminiello, M.; Schiavotto, C.; Parvis, G.; Zanotti, R.; Gini, G.; Ferreri, A.J.M.; Viero, P.; Miglino, M.; Billio, A.; Avigdor, A.; Biggi, A.; Fallanca, F.; Ficola, U.; Gregianin, M.; Chiaravalloti, A.; Prosperini, G.; Bergesio, F.; Chauvie, S.; Pavoni, C.; Gianni, A.M.; Rambaldi, A.

In: Journal of Clinical Oncology, Vol. 36, No. 5, 2018, p. 454-462.

Research output: Contribution to journalArticle

Gallamini, A, Tarella, C, Viviani, S, Rossi, A, Patti, C, Mule, A, Picardi, M, Romano, A, Cantonetti, M, Nasa, GL, Trentin, L, Bolis, S, Rapezzi, D, Battistini, R, Gottardi, D, Gavarotti, P, Corradini, P, Cimminiello, M, Schiavotto, C, Parvis, G, Zanotti, R, Gini, G, Ferreri, AJM, Viero, P, Miglino, M, Billio, A, Avigdor, A, Biggi, A, Fallanca, F, Ficola, U, Gregianin, M, Chiaravalloti, A, Prosperini, G, Bergesio, F, Chauvie, S, Pavoni, C, Gianni, AM & Rambaldi, A 2018, 'Early chemotherapy intensification with escalated beacopp in patients with advanced-stage hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two abvd cycles: Long-term results of the GITIL/FIL HD 0607 trial', Journal of Clinical Oncology, vol. 36, no. 5, pp. 454-462. https://doi.org/10.1200/JCO.2017.75.2543
Gallamini, A. ; Tarella, C. ; Viviani, S. ; Rossi, A. ; Patti, C. ; Mule, A. ; Picardi, M. ; Romano, A. ; Cantonetti, M. ; Nasa, G.L. ; Trentin, L. ; Bolis, S. ; Rapezzi, D. ; Battistini, R. ; Gottardi, D. ; Gavarotti, P. ; Corradini, P. ; Cimminiello, M. ; Schiavotto, C. ; Parvis, G. ; Zanotti, R. ; Gini, G. ; Ferreri, A.J.M. ; Viero, P. ; Miglino, M. ; Billio, A. ; Avigdor, A. ; Biggi, A. ; Fallanca, F. ; Ficola, U. ; Gregianin, M. ; Chiaravalloti, A. ; Prosperini, G. ; Bergesio, F. ; Chauvie, S. ; Pavoni, C. ; Gianni, A.M. ; Rambaldi, A. / Early chemotherapy intensification with escalated beacopp in patients with advanced-stage hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two abvd cycles: Long-term results of the GITIL/FIL HD 0607 trial. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 5. pp. 454-462.
@article{63feaccd2d1f4bfbbd6a6b9c97f8d25f,
title = "Early chemotherapy intensification with escalated beacopp in patients with advanced-stage hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two abvd cycles: Long-term results of the GITIL/FIL HD 0607 trial",
abstract = "Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≤ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19{\%}) had a positive and 630 (81{\%}) a negative PET2. The 3-year PFS of all patients was 82{\%}. The 3-year PFS of those with a positive and negative PET2 was 60{\%} and 87{\%}, respectively (P > .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63{\%} versus 57{\%} (P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97{\%} v 93{\%}, respectively; P = .29). The 3-year overall survival of all 782 patients was 97{\%} (99{\%} and 89{\%} for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL. {\circledC} 2018 by American Society of Clinical Oncology.",
keywords = "alanine aminotransferase, antineoplastic agent, aspartate aminotransferase, bleomycin, cyclophosphamide, dacarbazine, doxorubicin, etoposide, fluorodeoxyglucose f 18, prednisone, procarbazine, rituximab, vinblastine, vincristine, add on therapy, adolescent, adult, advanced cancer, alanine aminotransferase blood level, Article, aspartate aminotransferase blood level, blood clotting disorder, blood toxicity, bone marrow toxicity, cancer combination chemotherapy, cancer growth, cancer mortality, cancer patient, cancer radiotherapy, cancer regression, cancer survival, classical Hodgkin lymphoma, controlled study, drug dose escalation, drug dose intensification, drug hypersensitivity, drug substitution, drug treatment failure, drug withdrawal, early intervention, event free survival, female, gastrointestinal infection, heart failure, hepatobiliary disease, human, long term survival, lung fibrosis, lung infection, lung toxicity, male, metabolic disorder, multiple cycle treatment, musculoskeletal disease, nausea and vomiting, neurotoxicity, neutropenia, open study, overall survival, pain, pancreas disease, phase 2 clinical trial, positron emission tomography-computed tomography, priority journal, progression free survival, randomized controlled trial, side effect, skin toxicity, soft tissue disease, treatment response, vascular disease, young adult",
author = "A. Gallamini and C. Tarella and S. Viviani and A. Rossi and C. Patti and A. Mule and M. Picardi and A. Romano and M. Cantonetti and G.L. Nasa and L. Trentin and S. Bolis and D. Rapezzi and R. Battistini and D. Gottardi and P. Gavarotti and P. Corradini and M. Cimminiello and C. Schiavotto and G. Parvis and R. Zanotti and G. Gini and A.J.M. Ferreri and P. Viero and M. Miglino and A. Billio and A. Avigdor and A. Biggi and F. Fallanca and U. Ficola and M. Gregianin and A. Chiaravalloti and G. Prosperini and F. Bergesio and S. Chauvie and C. Pavoni and A.M. Gianni and A. Rambaldi",
note = "Cited By :17 Export Date: 5 February 2019 CODEN: JCOND Correspondence Address: Rambaldi, A.; Universita degli Studi di Milano, Piazza OMS, 1, Italy; email: alessandro.rambaldi@unimi.it Chemicals/CAS: alanine aminotransferase, 9000-86-6, 9014-30-6; aspartate aminotransferase, 9000-97-9; bleomycin, 11056-06-7, 9041-93-4; cyclophosphamide, 50-18-0; dacarbazine, 4342-03-4; doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0, 433304-61-1; fluorodeoxyglucose f 18, 63503-12-8; prednisone, 53-03-2; procarbazine, 366-70-1, 671-16-9; rituximab, 174722-31-7; vinblastine, 865-21-4; vincristine, 57-22-7 References: Canellos, G.P., Anderson, J.R., Propert, K.J., Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD (1992) N Engl J Med, 327, pp. 1478-1484; Diehl, V., Franklin, J., Pfreundschuh, M., Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease (2003) N Engl J Med, 348, pp. 2386-2395; (2005) N Engl J Med, 353, p. 744. , Erratum; Duggan, D.B., Petroni, G.R., Johnson, J.L., Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: Report of an intergroup trial (2003) J Clin Oncol, 21, pp. 607-614; Federico, M., Luminari, S., Iannitto, E., ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: Results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial (2009) J Clin Oncol, 27, pp. 805-811; Gordon, L.I., Hong, F., Fisher, R.I., Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: An intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496) (2013) J Clin Oncol, 31, pp. 684-691; Hoskin, P.J., Lowry, L., Horwich, A., Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin's lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 (2009) J Clin Oncol, 27, pp. 5390-5396; Viviani, S., Zinzani, P.L., Rambaldi, A., ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned (2011) N Engl J Med, 365, pp. 203-212; Bonfante, V., Santoro, A., Viviani, S., ABVD in the treatment of Hodgkin's disease (1992) Semin Oncol, 19, pp. 38-44. , discussion 44-45; Engert, A., Diehl, V., Franklin, J., Escalateddose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study (2009) J Clin Oncol, 27, pp. 4548-4554; Engert, A., Haverkamp, H., Kobe, C., Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial (2012) Lancet, 379, pp. 1791-1799; Behringer, K., Breuer, K., Reineke, T., Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: A report from the German Hodgkin's Lymphoma Study Group (2005) J Clin Oncol, 23, pp. 7555-7564; Behringer, K., Mueller, H., Goergen, H., Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials (2013) J Clin Oncol, 31, pp. 231-239; Sieniawski, M., Reineke, T., Nogova, L., Fertility in male patients with advanced Hodgkin lymphoma treated with BEACOPP: A report of the German Hodgkin Study Group (GHSG) (2008) Blood, 111, pp. 71-76; Josting, A., Wiedenmann, S., Franklin, J., Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: A report from the German Hodgkin's Lymphoma Study Group (2003) J Clin Oncol, 21, pp. 3440-3446; Kostakoglu, L., Goldsmith, S.J., Leonard, J.P., FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease (2006) Cancer, 107, pp. 2678-2687; Hutchings, M., Kostakoglu, L., Zaucha, J.M., In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma (2014) J Clin Oncol, 32, pp. 2705-2711; Hutchings, M., Loft, A., Hansen, M., FDGPET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma (2006) Blood, 107, pp. 52-59; Gallamini, A., Hutchings, M., Rigacci, L., Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: A report from a joint Italian-Danish study (2007) J Clin Oncol, 25, pp. 3746-3752; Hryniuk, W.M., Goodyear, M., The calculation of received dose intensity (1990) J Clin Oncol, 8, pp. 1935-1937; Longo, D.L., Duffey, P.L., DeVita, V.T., Jr., The calculation of actual or received dose intensity: A comparison of published methods (1991) J Clin Oncol, 9, pp. 2042-2051; Chauvie, S., Biggi, A., Stancu, A., WIDEN: A tool for medical image management in multicenter clinical trials (2014) Clin Trials, 11, pp. 355-361; Biggi, A., Gallamini, A., Chauvie, S., International validation study for interim PET in ABVDtreated, advanced-stage Hodgkin lymphoma: Interpretation criteria and concordance rate among reviewers (2013) J Nucl Med, 54, pp. 683-690; Meignan, M., Gallamini, A., Meignan, M., Report on the first international workshop on interim-PET-Scan in Lymphoma (2009) Leuk Lymphoma, 50, pp. 1257-1260; Dodd, L.E., Korn, E.L., Freidlin, B., Blinded independent central review of progression-free survival in phase III clinical trials: Important design element or unnecessary expense (2008) J Clin Oncol, 26, pp. 3791-3796; Press, O.W., Li, H., Sch{\"o}der, H., US intergroup trial of response-adapted therapy for stage III to IV Hodgkin lymphoma using early interim fluorodeoxyglucose-positron emission tomography imaging: Southwest Oncology Group S0816 (2016) J Clin Oncol, 34, pp. 2020-2027; Zinzani, P.L., Broccoli, A., Gioia, D.M., Interim positron emission tomography response-adapted therapy in advanced-stage Hodgkin lymphoma: Final results of the phase II part of the HD0801 study (2016) J Clin Oncol, 34, pp. 1376-1385; Ansell, S.M., Lesokhin, A.M., Borrello, I., PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma (2015) N Engl J Med, 372, pp. 311-319; Younes, A., Connors, J.M., Park, S.I., Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: A phase 1, open-label, dose-escalation study (2013) Lancet Oncol, 14, pp. 1348-1356; Avigdor, A., Bulvik, S., Levi, I., Two cycles of escalated BEACOPP followed by four cycles of ABVD utilizing early-interim PET/CT scan is an effective regimen for advanced high-risk Hodgkin's lymphoma (2010) Ann Oncol, 21, pp. 126-132; Hasenclever, D., Diehl, V., A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease (1998) N Engl J Med, 339, pp. 1506-1514; Moccia, A.A., Donaldson, J., Chhanabhai, M., International Prognostic Score in advanced-stage Hodgkin's lymphoma: Altered utility in the modern era (2012) J Clin Oncol, 30, pp. 3383-3388; Johnson, P., Federico, M., Kirkwood, A., Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma (2016) N Engl J Med, 374, pp. 2419-2429; Younes, A., Oki, Y., McLaughlin, P., Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma (2012) Blood, 119, pp. 4123-4128; Borchmann, P., Haverkamp, H., Lohri, A., Progression-free survival of early interim PETpositive patients with advanced stage Hodgkin's lymphoma treated with BEACOPP escalated alone or in combination with rituximab (HD18): An open-label, international, randomised phase 3 study by the German Hodgkin Study Group (2017) Lancet Oncol, 18, pp. 454-463; Van Nimwegen, F.A., Ntentas, G., Darby, S.C., Risk of heart failure in survivors of Hodgkin lymphoma: Effects of cardiac exposure to radiation and anthracyclines (2017) Blood, 129, pp. 2257-2265; Schaapveld, M., Aleman, B.M.P., Van Eggermond, A.M., Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma (2015) N Engl J Med, 373, pp. 2499-2511; Borchmann, P., Haverkamp, H., Diehl, V., 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 (2011) J Clin Oncol, 29, pp. 4234-4242; Johnson, P.W., Response-adapted frontline therapy for Hodgkin lymphoma: Are we there yet (2016) Hematology (Am Soc Hematol Educ Program), 2016, pp. 316-322",
year = "2018",
doi = "10.1200/JCO.2017.75.2543",
language = "English",
volume = "36",
pages = "454--462",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "5",

}

TY - JOUR

T1 - Early chemotherapy intensification with escalated beacopp in patients with advanced-stage hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two abvd cycles: Long-term results of the GITIL/FIL HD 0607 trial

AU - Gallamini, A.

AU - Tarella, C.

AU - Viviani, S.

AU - Rossi, A.

AU - Patti, C.

AU - Mule, A.

AU - Picardi, M.

AU - Romano, A.

AU - Cantonetti, M.

AU - Nasa, G.L.

AU - Trentin, L.

AU - Bolis, S.

AU - Rapezzi, D.

AU - Battistini, R.

AU - Gottardi, D.

AU - Gavarotti, P.

AU - Corradini, P.

AU - Cimminiello, M.

AU - Schiavotto, C.

AU - Parvis, G.

AU - Zanotti, R.

AU - Gini, G.

AU - Ferreri, A.J.M.

AU - Viero, P.

AU - Miglino, M.

AU - Billio, A.

AU - Avigdor, A.

AU - Biggi, A.

AU - Fallanca, F.

AU - Ficola, U.

AU - Gregianin, M.

AU - Chiaravalloti, A.

AU - Prosperini, G.

AU - Bergesio, F.

AU - Chauvie, S.

AU - Pavoni, C.

AU - Gianni, A.M.

AU - Rambaldi, A.

N1 - Cited By :17 Export Date: 5 February 2019 CODEN: JCOND Correspondence Address: Rambaldi, A.; Universita degli Studi di Milano, Piazza OMS, 1, Italy; email: alessandro.rambaldi@unimi.it Chemicals/CAS: alanine aminotransferase, 9000-86-6, 9014-30-6; aspartate aminotransferase, 9000-97-9; bleomycin, 11056-06-7, 9041-93-4; cyclophosphamide, 50-18-0; dacarbazine, 4342-03-4; doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0, 433304-61-1; fluorodeoxyglucose f 18, 63503-12-8; prednisone, 53-03-2; procarbazine, 366-70-1, 671-16-9; rituximab, 174722-31-7; vinblastine, 865-21-4; vincristine, 57-22-7 References: Canellos, G.P., Anderson, J.R., Propert, K.J., Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD (1992) N Engl J Med, 327, pp. 1478-1484; Diehl, V., Franklin, J., Pfreundschuh, M., Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease (2003) N Engl J Med, 348, pp. 2386-2395; (2005) N Engl J Med, 353, p. 744. , Erratum; Duggan, D.B., Petroni, G.R., Johnson, J.L., Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: Report of an intergroup trial (2003) J Clin Oncol, 21, pp. 607-614; Federico, M., Luminari, S., Iannitto, E., ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: Results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial (2009) J Clin Oncol, 27, pp. 805-811; Gordon, L.I., Hong, F., Fisher, R.I., Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: An intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496) (2013) J Clin Oncol, 31, pp. 684-691; Hoskin, P.J., Lowry, L., Horwich, A., Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin's lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 (2009) J Clin Oncol, 27, pp. 5390-5396; Viviani, S., Zinzani, P.L., Rambaldi, A., ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned (2011) N Engl J Med, 365, pp. 203-212; Bonfante, V., Santoro, A., Viviani, S., ABVD in the treatment of Hodgkin's disease (1992) Semin Oncol, 19, pp. 38-44. , discussion 44-45; Engert, A., Diehl, V., Franklin, J., Escalateddose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study (2009) J Clin Oncol, 27, pp. 4548-4554; Engert, A., Haverkamp, H., Kobe, C., Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial (2012) Lancet, 379, pp. 1791-1799; Behringer, K., Breuer, K., Reineke, T., Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: A report from the German Hodgkin's Lymphoma Study Group (2005) J Clin Oncol, 23, pp. 7555-7564; Behringer, K., Mueller, H., Goergen, H., Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials (2013) J Clin Oncol, 31, pp. 231-239; Sieniawski, M., Reineke, T., Nogova, L., Fertility in male patients with advanced Hodgkin lymphoma treated with BEACOPP: A report of the German Hodgkin Study Group (GHSG) (2008) Blood, 111, pp. 71-76; Josting, A., Wiedenmann, S., Franklin, J., Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: A report from the German Hodgkin's Lymphoma Study Group (2003) J Clin Oncol, 21, pp. 3440-3446; Kostakoglu, L., Goldsmith, S.J., Leonard, J.P., FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease (2006) Cancer, 107, pp. 2678-2687; Hutchings, M., Kostakoglu, L., Zaucha, J.M., In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma (2014) J Clin Oncol, 32, pp. 2705-2711; Hutchings, M., Loft, A., Hansen, M., FDGPET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma (2006) Blood, 107, pp. 52-59; Gallamini, A., Hutchings, M., Rigacci, L., Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: A report from a joint Italian-Danish study (2007) J Clin Oncol, 25, pp. 3746-3752; Hryniuk, W.M., Goodyear, M., The calculation of received dose intensity (1990) J Clin Oncol, 8, pp. 1935-1937; Longo, D.L., Duffey, P.L., DeVita, V.T., Jr., The calculation of actual or received dose intensity: A comparison of published methods (1991) J Clin Oncol, 9, pp. 2042-2051; Chauvie, S., Biggi, A., Stancu, A., WIDEN: A tool for medical image management in multicenter clinical trials (2014) Clin Trials, 11, pp. 355-361; Biggi, A., Gallamini, A., Chauvie, S., International validation study for interim PET in ABVDtreated, advanced-stage Hodgkin lymphoma: Interpretation criteria and concordance rate among reviewers (2013) J Nucl Med, 54, pp. 683-690; Meignan, M., Gallamini, A., Meignan, M., Report on the first international workshop on interim-PET-Scan in Lymphoma (2009) Leuk Lymphoma, 50, pp. 1257-1260; Dodd, L.E., Korn, E.L., Freidlin, B., Blinded independent central review of progression-free survival in phase III clinical trials: Important design element or unnecessary expense (2008) J Clin Oncol, 26, pp. 3791-3796; Press, O.W., Li, H., Schöder, H., US intergroup trial of response-adapted therapy for stage III to IV Hodgkin lymphoma using early interim fluorodeoxyglucose-positron emission tomography imaging: Southwest Oncology Group S0816 (2016) J Clin Oncol, 34, pp. 2020-2027; Zinzani, P.L., Broccoli, A., Gioia, D.M., Interim positron emission tomography response-adapted therapy in advanced-stage Hodgkin lymphoma: Final results of the phase II part of the HD0801 study (2016) J Clin Oncol, 34, pp. 1376-1385; Ansell, S.M., Lesokhin, A.M., Borrello, I., PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma (2015) N Engl J Med, 372, pp. 311-319; Younes, A., Connors, J.M., Park, S.I., Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: A phase 1, open-label, dose-escalation study (2013) Lancet Oncol, 14, pp. 1348-1356; Avigdor, A., Bulvik, S., Levi, I., Two cycles of escalated BEACOPP followed by four cycles of ABVD utilizing early-interim PET/CT scan is an effective regimen for advanced high-risk Hodgkin's lymphoma (2010) Ann Oncol, 21, pp. 126-132; Hasenclever, D., Diehl, V., A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease (1998) N Engl J Med, 339, pp. 1506-1514; Moccia, A.A., Donaldson, J., Chhanabhai, M., International Prognostic Score in advanced-stage Hodgkin's lymphoma: Altered utility in the modern era (2012) J Clin Oncol, 30, pp. 3383-3388; Johnson, P., Federico, M., Kirkwood, A., Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma (2016) N Engl J Med, 374, pp. 2419-2429; Younes, A., Oki, Y., McLaughlin, P., Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma (2012) Blood, 119, pp. 4123-4128; Borchmann, P., Haverkamp, H., Lohri, A., Progression-free survival of early interim PETpositive patients with advanced stage Hodgkin's lymphoma treated with BEACOPP escalated alone or in combination with rituximab (HD18): An open-label, international, randomised phase 3 study by the German Hodgkin Study Group (2017) Lancet Oncol, 18, pp. 454-463; Van Nimwegen, F.A., Ntentas, G., Darby, S.C., Risk of heart failure in survivors of Hodgkin lymphoma: Effects of cardiac exposure to radiation and anthracyclines (2017) Blood, 129, pp. 2257-2265; Schaapveld, M., Aleman, B.M.P., Van Eggermond, A.M., Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma (2015) N Engl J Med, 373, pp. 2499-2511; Borchmann, P., Haverkamp, H., Diehl, V., 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 (2011) J Clin Oncol, 29, pp. 4234-4242; Johnson, P.W., Response-adapted frontline therapy for Hodgkin lymphoma: Are we there yet (2016) Hematology (Am Soc Hematol Educ Program), 2016, pp. 316-322

PY - 2018

Y1 - 2018

N2 - Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≤ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively (P > .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% (P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL. © 2018 by American Society of Clinical Oncology.

AB - Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≤ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively (P > .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% (P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL. © 2018 by American Society of Clinical Oncology.

KW - alanine aminotransferase

KW - antineoplastic agent

KW - aspartate aminotransferase

KW - bleomycin

KW - cyclophosphamide

KW - dacarbazine

KW - doxorubicin

KW - etoposide

KW - fluorodeoxyglucose f 18

KW - prednisone

KW - procarbazine

KW - rituximab

KW - vinblastine

KW - vincristine

KW - add on therapy

KW - adolescent

KW - adult

KW - advanced cancer

KW - alanine aminotransferase blood level

KW - Article

KW - aspartate aminotransferase blood level

KW - blood clotting disorder

KW - blood toxicity

KW - bone marrow toxicity

KW - cancer combination chemotherapy

KW - cancer growth

KW - cancer mortality

KW - cancer patient

KW - cancer radiotherapy

KW - cancer regression

KW - cancer survival

KW - classical Hodgkin lymphoma

KW - controlled study

KW - drug dose escalation

KW - drug dose intensification

KW - drug hypersensitivity

KW - drug substitution

KW - drug treatment failure

KW - drug withdrawal

KW - early intervention

KW - event free survival

KW - female

KW - gastrointestinal infection

KW - heart failure

KW - hepatobiliary disease

KW - human

KW - long term survival

KW - lung fibrosis

KW - lung infection

KW - lung toxicity

KW - male

KW - metabolic disorder

KW - multiple cycle treatment

KW - musculoskeletal disease

KW - nausea and vomiting

KW - neurotoxicity

KW - neutropenia

KW - open study

KW - overall survival

KW - pain

KW - pancreas disease

KW - phase 2 clinical trial

KW - positron emission tomography-computed tomography

KW - priority journal

KW - progression free survival

KW - randomized controlled trial

KW - side effect

KW - skin toxicity

KW - soft tissue disease

KW - treatment response

KW - vascular disease

KW - young adult

U2 - 10.1200/JCO.2017.75.2543

DO - 10.1200/JCO.2017.75.2543

M3 - Article

VL - 36

SP - 454

EP - 462

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 5

ER -