Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease.
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.
Hamilton
V M
VM
Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Norris
C
C
Bunin
N
N
Goldwein
J W
JW
Bunin
G R
GR
Lange
B
B
Meadows
A T
AT
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
D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone