Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease.

Abstract

PURPOSE:

The outlook for children and adolescents with Hodgkin disease (HD) is excellent with combined modality therapy. However, the long-term toxicities of multiagent therapy and radiation therapy remain of concern for these patients with curable disease. In an attempt to reduce long-term toxicities while preserving excellent cure rates, we developed a combined-modality protocol using a modified seven-drug hybrid and low-dose (2,000 cGy) involved field radiation therapy (RT). The hybrid used cumulative doses of alkylating agents and anthracyclines that were lower than those used in previous four-drug regimens and substituted a less leukemogenic agent, cyclophosphamide, for nitrogen mustard.

PATIENTS AND METHODS:

From 1991 through 1994 a cyclophosphamide, vincristine, procarbazine, and prednisone/adriamycin, bleomycin, and vinblastine hybrid was used to treat 29 patients with HD. Median age was 12 years (range 6-16 yrs). Patients who were postpubertal with early stage disease as determined by surgical staging were excluded. Treatment consisted of four cycles of therapy for stages I and IIA, six cycles for stages IIB and III, and eight cycles for stage IV. Twenty-two patients also received low-dose RT to areas of bulky disease.

RESULTS:

Twenty-eight patients (97%) had a complete response to chemotherapy. Five patients experienced relapse; two died from disease 27 and 29 months after initial diagnosis; three received additional therapy and are alive with no evidence of disease. Follow-up for all other patients is a median of 56 months (range 24-78 mos) from cessation of therapy and all have remained disease-free. At 5 years follow-up, actuarial disease-free survival is 82%, and the overall survival is 93%. There have been no clinically significant cardiac or pulmonary toxicities and no secondary malignancies.

CONCLUSIONS:

This therapy has resulted in 5-year overall survival and disease-free survival rates similar to regimens using higher doses of alkylating agents, anthracyclines, and radiation. Longer follow-up will be necessary to fully evaluate disease-free survival, organ damage, and quality of life.

• Authors: V M Hamilton, C Norris, N Bunin, J W Goldwein, G R Bunin, B Lange, A T Meadows
• Journal: Journal of pediatric hematology/oncology (J Pediatr Hematol Oncol) Vol. 23 Issue 2 Pg. 84-8 (Feb 2001) ISSN: 1077-4114 [Print] United States
• PMID: 11216711 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Bleomycin
• Procarbazine
• Vincristine
• Vinblastine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bleomycin (administration & dosage, adverse effects)
• Child
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage, adverse effects)
• Disease-Free Survival
• Doxorubicin (administration & dosage, adverse effects)
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation
• Hodgkin Disease (drug therapy, mortality, pathology, radiotherapy)
• Humans
• Hypothyroidism (etiology)
• Male
• Neoplasm Staging
• Neoplasms, Second Primary (etiology, prevention & control)
• Neutropenia (chemically induced)
• Prednisone (administration & dosage, adverse effects)
• Procarbazine (administration & dosage, adverse effects)
• Puberty, Delayed (etiology)
• Radiotherapy Dosage
• Radiotherapy, Adjuvant (adverse effects)
• Remission Induction
• Survival Rate
• Thrombocytopenia (chemically induced)
• Treatment Outcome
• Vinblastine (administration & dosage, adverse effects)
• Vincristine (administration & dosage, adverse effects)