HIGH-DOSE IFOSFAMIDE WITH HEMATOPOIETIC GROWTH FACTOR SUPPORT IN ADVANCED BONE AND SOFT TISSUE SARCOMAS
Bulent Yalcin, Ali Pamir, Abdullah Buyukcelik,
Gungor Utkan, Hakan Akbulut, Ahmet Demirkazik, Fikri Icli
Department of Medical Oncology, Ankara University School of Medicine Sihhiye, Ankara 06100, Turkey
Abstract. Aim: Ifosfamide and doxorubicin are the most effective agents in the treatment of sarcomas, although their contributions to survival are usually limited.
High-dose ifosfamide can be used as a salvage treatment in patients with recurrent or advanced sarcoma. We evaluated efficacy and toxicity of high-dose
ifosfamide in the patients with recurrent or advanced sarcoma in this study. Methods: 39 patients with recurrent or advanced sarcoma were enrolled
onto the study between 1996 and 2002. All patients had histological proven high grade sarcoma with measurable or evaluable disease. Ifosfamide was
administered at the dose of 2 g/m2 as continuous intravenous infusion for 24 h on day 1–9, in conjuction with the continuous
infusion of mesna. Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor was given every cycle. The efficacy and toxicity
of high dose ifosfamide (HDI) were evaluated clinically before subsequent cycle. The objective response was evaluated every two cycles. Histopathologic response
was also evaluated in patients who underwent surgical resection. Results: Male/female ratio was 24/15, with a median age of 20 (11–48) years. 9 patients
had locally inoperable advanced disease and 30 patients had metastatic disease. 10 patients were chemo-naive. The total number of HDI-chemotherapy cycles
was 103 (median 2 cycles (range, 1 to 7)). 2 patients refused the further treatment after the first cycle and 1 patient died due to neutropenic sepsis in the first cycle
of treatment. 36 patients were avaliable for the evaluation of treatment efficacy. Overall response rates were 53.8% and 90% in pre-treated patients and in chemo-naive
patients, respectively. Median follow-up time was 43 months. 13 patients underwent total surgical tumor resection. Pathologic complete response was observed in
5 of 13 these patients who underwent surgery. Median progression-free survival (PFS) was 7 months (95%CI: 3.8-10.2). The median progression-free survival (PFS)
were 3 and 12 months in patients who did not have tumor resection, and in those having complete tumor resection (p = 0.002). Median overall survival (OS)
was 10 months (95%CI: 0.0-20) in all patients. Median OS times were 8 months in patients without tumor resection and 26.5 months in patients with those underwent
surgical treatment (p = 0.0369). 2 patients who underwent surgery are still alive and disease-free. Major toxicity was myelosupression. Conclusion: HDI
seems to be feasible and effective in selected patients with advanced or recurrent sarcomas. Survival advantage of HDI is better when the total tumor resection can be done.
Key Words:bone and soft tissue sarcoma, advanced disease, high-dose ifosfamide.
