title: Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Hamilton
authors.forename: C
authors.initials: C
authors.lastname: Norris
authors.forename: N
authors.initials: N
authors.lastname: Bunin
authors.forename: J W
authors.initials: JW
authors.lastname: Goldwein
authors.forename: G R
authors.initials: GR
authors.lastname: Bunin
authors.forename: B
authors.initials: B
authors.lastname: Lange
authors.forename: A T
authors.initials: AT
authors.lastname: Meadows
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology; D008297:Male; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000517:prevention & control; D009503:Neutropenia / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D011628:Puberty, Delayed / Q000209:etiology; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012074:Remission Induction; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone