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Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol 2014 Nov 10;32(32):3651-8

Date

10/15/2014

Pubmed ID

25311218

Pubmed Central ID

PMC4220044

DOI

10.1200/JCO.2013.52.5410

Scopus ID

2-s2.0-84911866817   90 Citations

Abstract

PURPOSE: The Children's Oncology Group study AHOD0031, a randomized phase III study, was designed to evaluate the role of early chemotherapy response in tailoring subsequent therapy in pediatric intermediate-risk Hodgkin lymphoma. To avoid treatment-associated risks that compromise long-term health and to maintain high cure rates, dose-intensive chemotherapy with limited cumulative doses was used.

PATIENTS AND METHODS: Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, and prednisone (ABVE-PC) followed by response evaluation. Rapid early responders (RERs) received two additional ABVE-PC cycles, followed by complete response (CR) evaluation. RERs with CR were randomly assigned to involved-field radiotherapy (IFRT) or no additional therapy; RERs with less than CR were nonrandomly assigned to IFRT. Slow early responders (SERs) were randomly assigned to receive two additional ABVE-PC cycles with or without two cycles of dexamethasone, etoposide, cisplatin, and cytarabine (DECA). All SERs were assigned to receive IFRT.

RESULTS: Among 1,712 eligible patients, 4-year event-free survival (EFS) was 85.0%: 86.9% for RERs and 77.4% for SERs (P < .001). Four-year overall survival was 97.8%: 98.5% for RERs and 95.3% for SERs (P < .001). Four-year EFS was 87.9% versus 84.3% (P = .11) for RERs with CR who were randomly assigned to IFRT versus no IFRT, and 86.7% versus 87.3% (P = .87) for RERs with positron emission tomography (PET) -negative results at response assessment. Four-year EFS was 79.3% versus 75.2% (P = .11) for SERs who were randomly assigned to DECA versus no DECA, and 70.7% versus 54.6% (P = .05) for SERs with PET-positive results at response assessment.

CONCLUSION: This trial demonstrated that early response assessment supported therapeutic titration (omitting radiotherapy in RERs with CR; augmenting chemotherapy in SERs with PET-positive disease). Strategies directed toward improved response assessment and risk stratification may enhance tailoring of treatment to patient characteristics and response.

Author List

Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL

Author

Cindy L. Schwartz MD, MPH Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Antineoplastic Combined Chemotherapy Protocols
Bleomycin
Child
Child, Preschool
Cisplatin
Combined Modality Therapy
Cyclophosphamide
Cytarabine
Dexamethasone
Disease-Free Survival
Dose-Response Relationship, Drug
Doxorubicin
Etoposide
Female
Hodgkin Disease
Humans
Infant
Infant, Newborn
Male
Prednisone
Remission Induction
Risk Factors
Treatment Outcome
Vincristine
Young Adult
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab