Use of 5-Fluorouracil in the Management of Advanced Malignancies in Childhood

Abstract

associates in 1957 specifically designed 5 \ x = r e q -\ fluorouracil as an antimetabolite for cancer chemotherapy.1,2 Beneficial effects of 5-x =r eq-\ fluorouracil on experimental animal cancers were obtained.3 Subsequent clinical trials have indicated the efficacy of 5-fluorouracil (5-FU) in treatment of hepatoma, cancer of colon, rectum, and breast.Murphy6 and Wolman7 have reported the use of 5-fluoro-2\m='\-deoxyuridine in the treatment of leukemia and neoplasms of childhood. Ansfield8 has noted that the 5-FU compounds produce less toxicity in children than in adults.This clinical study is a report of 16 children who have received 5-FU for advanced or disseminated malignancies. The disappearance and reduction in size of malignancies following 5-FU have been remarkable. Complete regression of tumor has been noted in one patient with sarcoma of the larynx and in one patient with lymphosarcoma of the abdomen. Methods and MaterialsAll the patients treated in this series had the diagnosis confirmed by microscopic section.* Surgical and radiation therapy have been fully utilized prior to the use of 5-FU. Fourteen patients have had métastases distant from the site of the origi¬ nal tumor. One had progressive local uncon¬ trollable growth of sarcoma of the larynx.Evidence of regression was considered when there was objective roentgenographic decrease or disappearance of bone and/or pulmonary metastases. Change in size of tumor as noted by pal¬ pation or visualization was accepted only when clearly supported by measurement and examination by several observers.The dosage of 5-FU was 15 mg/kg/day for five days, given intravenously. If no serious toxic signs were manifest, repeated courses of therapy were given. Dosage was also increased in several instances to 25 and 30 mg/kg/day. Toxicity was manifested most frequently by nausea and vomiting. Periodic examination of the mouth was done to determine the incidence of severe oral mucous membrane ulcers. Determina¬ tions of total white cells, differential, platelets, and hemoglobin were done at frequent intervals.

Phase II trial of sequential methotrexate and 5-fluorouracil with leucovorin in children with sarcomas

“…In these studies, the toxicity of this combination has been mild and myelosuppression was minimal. Gastrointestinal toxicity (mucositis or diarrhea) was generally dose-limiting.Although sporadic responses to 5-FU and MTX have been reported in Ewing's and soft tissue sarcomas of childhood [5,6], neither drug has been studied systematically in this group of small round blue cell tumors of childhood. We undertook a phase II trial of sequential MTX (with leucovorin rescue) and 5-FU administered by continuous infusion.…”

DNA flow cytometric study of 5-fluorouracil used to treat end stage non-Hodgkin's lymphoma

“…Although 5-FU is considered an inactive drug in the treatment of NHL (Heidelberger, 1982), the total number of patients treated and subsequently reported is small, and the earlier literature does in fact show some responses (Ansfield et al, 1962;Krivit & Bentley, 1960 Table I. Two had diffuse large cell lymphoma, and two well differentiated diffuse lymphocytic lymphoma.…”

Treatment of metastatic Ewing's sarcoma with BCNU

“…1). These 3-day courses of BCNU were repeated starting April 14 and June 8,1964. There was complete disappearance of lung metastasis by chest x-ray following his second course of BCNU.…”