All-trans retinoic acid and interferon-alpha in the treatment of a patientwith resistant metastatic osteosarcoma - A case report

BACKGROUND. A boy age 14 years who was in complete remission from Stage IIB small cell osteosarcoma, which was misdiagnosed as Ewing sarcoma and conse quently was treated, developed inoperable lung metastases when he was off t herapy. He received second-line treatment for recurrent Ewing sarcoma, incl uding chemotherapy and radiotherapy, and obtained only a temporary response . A compassionate treatment with all-trans retinoic acid (ATRA) and interfe ron-cu (IFN alpha) was then undertaken. METHODS. The patient initially was treated according to the national SE91 p rotocol for nonmetastatic Ewing sarcoma. After a bilateral pulmonary recurr ence, he received second-line chemotherapy and irradiation of the largest m etastasis, with a temporary partial response. The patient was then treated with a combination of oral ATRA (90 mg/m(2) for 3 days per week) and subcut aneous IFN alpha (3 x 10(6) U/m(2) 5 days per week) for 4 months. The same therapy also was administered for the control of residual disease after sur gery for a total duration of 1 year of ATRA/IFN treatment. During the first 3 weeks of therapy ATRA pharmacokinetics were studied. RESULTS, After progression of the patient's disease, despite the administra tion of first-line and second-line chemotherapy, combined treatment with AT RA/IFN alpha( yielded a partial remission, which allowed surgical resection of the largest metastasis. The same therapy was effective in preventing tu mor recurrence after incomplete removal of the remaining metastases. Treatm ent was well tolerated, and the patient is in stable complete remission 14 months after the end of therapy. The pharmacokinetics results confirmed the indication of an intermittent schedule for oral ATRA therapy. CONCLUSIONS. ATRA/IFN alpha treatment may be considered as an alternative a pproach in the treatment of patients with metastatic osteosarcoma who have disease that is resistant to conventional chemotherapy and in the treatment of patients with minimal tumor residue. Cancer 2000;89:2661-6. (C) 2000 Am erican Cancer Society.