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.

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.

• Authors: Debra L Friedman, Lu Chen, Suzanne Wolden, Allen Buxton, Kathleen McCarten, Thomas J FitzGerald, Sandra Kessel, Pedro A De Alarcon, Allen R Chen, Nathan Kobrinsky, Peter Ehrlich, Robert E Hutchison, Louis S Constine, Cindy L Schwartz
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 32 Pg. 3651-8 (Nov 10 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25311218 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Cytarabine
• Bleomycin
• Vincristine
• Etoposide
• Dexamethasone
• Doxorubicin
• Cyclophosphamide
• Cisplatin
• Prednisone

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bleomycin (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Cisplatin (administration & dosage, adverse effects)
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage, adverse effects)
• Cytarabine (administration & dosage, adverse effects)
• Dexamethasone (administration & dosage, adverse effects)
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage, adverse effects)
• Etoposide (administration & dosage, adverse effects)
• Female
• Hodgkin Disease (drug therapy, pathology, radiotherapy)
• Humans
• Infant
• Infant, Newborn
• Male
• Prednisone (administration & dosage, adverse effects)
• Remission Induction
• Risk Factors
• Treatment Outcome
• Vincristine (administration & dosage, adverse effects)
• Young Adult