Single agent high-dose ifosfamide in refractory or relapsed osteosarcoma.

Abstract

e22006 Background: Osteosarcoma (OS) is the most common primary malignant neoplasm of the bone in children and adolescents, typically occurring in the metaphysis of long bones. Historically, patients were treated with surgical resection, but the addition of neoadjuvant chemotherapy over the last 50 years has greatly improved prognosis, with survival rates increasing from 20% to almost 70% for non-metastatic tumors. However, prognosis remains poor for patients with refractory or recurrent disease, and Ifosfamide containing regimens are the standard 2nd line chemotherapy. Ifosfamide has been utilized in various combinations with other chemotherapeutic agents including methotrexate, cisplatin and epirubicin with variable reported results. Alternatively, it has been used as a single agent at an escalated dose of 12-14 gm/m2 with improved response. However, high dose Ifosfamide (HDI) is associated with nephrotoxicity. We aim to evaluate our institution’s experience with single agent HDI in terms of both outcome and safety. Methods: This is a single institutional retrospective study conducted at the Children’s Hospital of Michigan. All pediatric patients up to age 21 years with refractory or relapsed osteosarcoma who received at least 2 cycles of HDI therapy after MAP over the course of 20 years were included. Progression free and event free survival were calculated. Nephrotoxicity was documented as per common terminology criteria for adverse events (CTCAE) v.50 grading. Results: A total of 46 charts were screened, 19 patients were found to have recurrent or refractory OS. 3 patients were only treated surgically. 16 patients received 2nd line chemotherapy with/without surgical resection. 13 patients received single agent HDI and were included in our analysis. The mean age at diagnosis was 13.78, with 6 recurrent and 7 refractory patients. Patients received an average of 5 cycles of HDI. At end of therapy, objective response rate was 46% and disease control rate was 61%. 5 patients in our analysis had reported nephrotoxicity, with 3 patients having transient grade 1 elevations in creatinine that improved while remaining on chemotherapy. 2 patients developed persistent grade I elevation of creatinine, both developed this nephrotoxicity after being off therapy for more than 1 year. Nephrotoxicity was associated with higher number of cycles of HDI, with these patients receiving at least 4 cycles. At this point of follow up, 3 patients are alive without evidence of disease at least 2 years after completion of chemotherapy. Conclusions: Our experience is consistent with prior reports that HDI is efficacious as single agent therapy for patients with osteosarcoma that is refractory or recurrent with acceptable nephrotoxicity. In our experience, nephrotoxicity occasionally developed months after the cessation of therapy. As such, long term follow up of survivors is necessary.