Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy

Abstract

Vincristine, actinomycin D, and cyclophosphamide (VAC) were administered to 14 patients with Ewing's sarcoma. The primary tumors were treated with radiation therapy and concurrent chemotherapy. Nine patients had no visible metastases at diagnosis: two died following the development of pulmonary metastases and the rest have been free of disease for periods varying from 4 months to 4 1/2 years following completion of treatment. This contrasts with a 27% survival in patients previously treated at this center with single agent chemotherapy. Five other patients had demonstrable metastases at diagnosis: VAC chemotherapy achieved complete regression of pulmonary metastases in three for 9, 9+ and 24+ months, respectively. Following disappearance of tumor in the latter two, pulmonary irradiation was administered in an attempt to consolidate the response, but tumor recurred 6 months later. These patients eventually died of widespread disease although survival appeared prolonged in comparison to that seen in past experience. Chemotherapy was well tolerated, although three patients developed hemorrhagic cystitis, necessitating discontinuation of cyclophosphamide. The data suggest the potential for prolonged control and an increase in the cure rate with this therapeutic approach.

High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors

“…This tumor is chemosensitive, and multimodal therapy has significantly improved outcome for patients with EFT (3-year survival rates 55-80%). [6][7][8][9][10] Despite these encouraging results, subgroups of patients who have a poor prognosis can be identified (survival of 10-30% at 3 years). Poor prognostic features at initial presentation include metastatic disease, particularly those with bone or BM involvement, bulky disease (48 cm diameter) at diagnosis, primary tumor involving axial (pelvic) or proximal (femur and humerus), shorter interval of EFS between diagnosis and relapse 6 and age older than 16 years.…”

Therapy for Ewing’s Sarcoma: King Faisal Specialist Hospital and Research Centre Experience

“…The five-year survival rate of the patients without metastases at diagnosis was 47.5%, not different from that reported by several investigators, 6,17 but lower than that described by others. 5,7,12 The factors contributing to low long-term survival rate in our patients included advanced stage of tumor at diagnosis and shorter duration of chemotherapy (median 8 months) because of lack of compliance, instead of 18 months of therapy administered by other institutions.…”

“…2 Megavoltage irradiation has significantly improved the long-term survival in patients with localized Ewing's sarcoma. 4,7 The efficacy of chemotherapy in the management of Ewing's sarcoma was noted 20 years ago when several studies showed that chemotherapy can induce remission in patients with advanced disease. 8,.11 Since a fair number of patients with localized Ewing's sarcoma develop systemic metastases despite local therapy, such as surgical resection or radiotherapy, chemotherapy was used in conjunction with radiotherapy with the hope of improving the long-term survival of these patients.…”

“…8,.11 Since a fair number of patients with localized Ewing's sarcoma develop systemic metastases despite local therapy, such as surgical resection or radiotherapy, chemotherapy was used in conjunction with radiotherapy with the hope of improving the long-term survival of these patients. 4,6,7,12,13 This multimodality treatment took advantage of the additive therapeutic effect of chemotherapy and radiotherapy on the tumor, while their adverse side effects on the normal tissues remained essentially unchanged. This study is a review of the experience in the therapy of Ewing's sarcoma at King Faisal Specialist Hospital and Research Centre (KFSH&RC).…”

An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance Patterns in Ewing Sarcoma

“…Heretofore, simply referred to as Ewing sarcoma, this sarcoma subtype is a highly aggressive malignancy of adolescents and young adults (7) that is rapidly fatal without effective multimodality treatment that includes surgery and/or radiation and extensive use of systemic chemotherapy. Although polychemotherapy has led to marked improvement in 5-year survival for patients diagnosed with localized Ewing sarcoma-approaching 80% with current generation clinical trials-those with metastatic disease or rapid tumor recurrence fare poorly and often quickly succumb to their disease (8)(9)(10)(11).…”