levoleucovorin and Sarcoma--Ewing

5-Fluorouracil (5-FU) activity for various carcinomas of adults has been enhanced through the synergistic effect of leucovorin. Few pediatric studies of 5-FU in pediatric patients have been previously reported.. Fifty-eight patients were treated with a 4-hour infusion of leucovorin, 400 mg/m2, administered daily for 5 days every 3-4 weeks. 5-Fluorouracil was administered by bolus injection 1 hour into each leucovorin infusion. Eleven adolescent patients with colorectal carcinoma, Stage 3 or 4, were treated with therapeutic intent, and other patients with a variety of drug-resistant pediatric solid neoplasms received similar treatment.. Patients with measurable disease of colorectal carcinoma responded favorably to 5-FU/leucovorin. Stable disease activity was seen with other tumor types. Specifically, there were no objective responses in 12 patients with Ewing's Sarcoma or 11 with osteosarcoma. There were 4 deaths in this study from causes related to toxicity. Nonfatal grade 3/4 toxicities included mucositis, rash, myelosuppression, nausea, vomiting, diarrhea, and infection.. The authors do not plan further evaluation of 5-FU/leucovorin in additional pediatric patients with colon cancer or other heavily pretreated malignant solid tumors and are presently treating their patients with colon carcinoma with 5-FU/leucovorin/interferon-alpha 2a.

Topics: Adolescent; Carcinoma; Child; Child, Preschool; Colorectal Neoplasms; Drug Administration Schedule; Drug Synergism; Female; Fluorouracil; Humans; Infant; Leucovorin; Male; Neoplasms; Osteosarcoma; Sarcoma, Ewing; Treatment Outcome

The authors propose alternative chemotherapy of osteosarcoma and Ewing's sarcoma in children. The aim of this proposal was elaboration of effective and, at the same time, less expensive and less toxic therapeutic regimens. The authors recommend open surgical biopsy with doxorubicin for 3 consecutive days as a protection against the released circulating neoplastic cells. After completion of histopathologic examination, one of two types of chemotherapy is chosen randomly. In osteosarcoma, there was induction chemotherapy for 4 or 9 weeks (according to the type of operation--conservative amputation or limb salvage surgery). In the I type of induction chemotherapy, high doses of methotrexate with vincristine and citrovorum factor rescue are administrated weekly, in the II type--the combination of BCD (bleomycin, cytoxan, actinomycin D) and CDDP (cisplatin). On the regimen of intensification chemotherapy decides the degree of tumour response to induction chemotherapy assessed as tumour necrosis in histopathologic examination. Maintenance chemotherapy is the same in two types of regimen and is continued for the period up to 2 years. The authors elaborated concomitantly the regimen of high methotrexate doses administration with rescue procedure in the case of elevated serum methotrexate levels, and regimen of cisplatin administration aiming at maximal patients protecting against the toxic effects of both drugs. In Ewing's sarcoma the randomisation differentiates between T-9 Rosen's regimen of chemotherapy and own modification of Memphis group regimen. The primary tumour is treated by radiotherapy with lower doses adjusted to the tumor response to induction chemotherapy (30-50 Gy or 50 Gy) and the irradiation port limited to the residual bone lesion plus a 2-3 centimeter margin. Surgical excision of bone with tumor depends on special tumor localisation as the clavicula, rib or fibula. The results of discussed treatment regimens will be subsequently published.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Neoplasms; Child; Combined Modality Therapy; Cyclophosphamide; Dactinomycin; Doxorubicin; Humans; Leucovorin; Methotrexate; Organoplatinum Compounds; Osteosarcoma; Sarcoma, Ewing; Vincristine

This is a retrospective review of five children with post-irradiation bone sarcoma (PIS). Age at PIS onset ranged between 10 and 17 years (median 11). They were treated with a chemotherapy regimen, similar to that in use for primary osteogenic sarcoma, consisting of vincristine and high-dose methotrexate alternated with cisplatinum and ifosfamide, given for 12 months.. In all children chemotherapy induced a complete clinical remission. Four of them were alive in continuous complete remission at 1, 2, 4, and 12 years from the diagnosis of bone sarcoma. One girl recurred 3 years from PIS diagnosis and was salvaged by repeating the same chemotherapy program: she remained alive in second complete remission 8 years from relapse.. In spite of an intensive treatment previously given for the primary tumor, this drug schedule proved to be feasible and short-term side effects were manageable. Chemotherapy alone, using an intensive regimen effective for primary osteogenic sarcoma, may be an adequate therapy for childhood post-irradiation sarcoma.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Female; Humans; Ifosfamide; Leucovorin; Male; Methotrexate; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Remission Induction; Retrospective Studies; Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing; Survivors; Vincristine

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Chromatography, High Pressure Liquid; Drug Administration Schedule; Drug Evaluation; Drug Synergism; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Methotrexate; Rhabdomyosarcoma; Sarcoma, Ewing

Topics: Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Leucovorin; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Remission, Spontaneous; Sarcoma, Ewing; Vincristine

Surgical extirpation of the primary tumor has traditionally been utilized as initial treatment for sarcomas in children. The present report, however, demonstrates that sarcomas are optimally treated by means of a coordianted multidisciplinary approach. The latter offers the potential for achieving improved survival and preservation of organs and limbs, particularly for structures of the head and neck, for extremities, and in the genitourinary system.

Topics: Adolescent; Age Factors; Antineoplastic Agents; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Doxorubicin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Leucovorin; Lymphatic Metastasis; Male; Methods; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms; Vincristine

Disseminated malignant disease should be approached with the intention of curing the patient. This requires a multidisciplinary approach. Essential to the successful application of multidisciplinary treatment is the administration of effective chemotherapy, which may achieve reduction in both microscopic disease and overt tumour. In Ewing's sarcoma, the latter should be treated also by irradiation. Limited areas of bulk tumour that have failed to respond or have responded only partially may be removed surgically. Chemotherapy and radiation therapy should be used extensively for palliation; surgery may be required occasionally for control of pain. The decision to treat palliatively should be reached only after patients have received multidisciplinary consultation.

Topics: Bone Neoplasms; Child; Cyclophosphamide; Dactinomycin; Doxorubicin; Humans; Leucovorin; Methotrexate; Osteosarcoma; Sarcoma, Ewing; Vincristine

The evolution of treatment for osteogenic sarcoma at the Memorial Sloan-Kettering Cancer Center is reviewed. The possible control of micrometastases by chemotherapy and the excision of macrometastases at single or multiple thoracotomies by the thoracic surgeon have added greatly to the salvage rate of this tumour. Intensive chemotherapy has made possible en bloc resection of bones involved by tumour, with preservation of the limb. Despite advances, however, amputation or en bloc resection is still necessary to control the primary tumour.

Topics: Adult; Amputation, Surgical; Bone Neoplasms; Child; Chondrosarcoma; Fibrosarcoma; Humans; Leucovorin; Methotrexate; Osteosarcoma; Sarcoma, Ewing

Topics: Age Factors; Bone Neoplasms; Chondrosarcoma; Cyclophosphamide; Dactinomycin; Doxorubicin; Humans; Leucovorin; Osteosarcoma; Sarcoma, Ewing; Vincristine

We have reviewed the literature and described experience in treating Ewing's sarcoma and osteosarcoma before and during the era of intensive systemic chemotherapy. Local control of Ewing's sarcoma may relate to increasing doses of radiation, especially when intensive chemotherapy is administered also. Problems of radiation enhancement by chemotherapy have caused us to reconsider time-dose and volume parameters in treating these patients. The role of radiation in osteogenic sarcoma is limited to patients with inoperable lesions and metastases.

Topics: Bone Neoplasms; Child; Cyclophosphamide; Dactinomycin; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Radiation Tolerance; Radiotherapy Dosage; Radiotherapy, High-Energy; Sarcoma, Ewing; Vincristine

Topics: Adolescent; Age Factors; Aspartate Aminotransferases; Child; Child, Preschool; Female; Half-Life; Hematopoiesis; Humans; Kidney; Leucovorin; Liposarcoma; Methotrexate; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Ovarian Neoplasms; Rhabdomyosarcoma; Sarcoma, Ewing; Teratoma