Neoadjuvant and adjuvant chemotherapy with high-dose ifosfamide, doxorubicin, cisplatin and high-dose methotrexate in non-metastatic osteosarcoma of the extremities: a phase II trial in Japan

Abstract

From 1997 to 2003, 40 patients (all <40 years of age) with non-metastatic osteosarcoma of the extremities were treated with OOS-D and definitive surgery. Two cycles of doxorubicin 90 mg/m(2) plus cisplatin 120 mg/m(2) and ifosfamide 15 g/m(2) were given as neoadjuvant chemotherapy, and two cycles of doxorubicin/cisplatin and ifosfamide, and two cycles of high-dose methotrexate (10-12 g/m(2)) were given post-operatively. All patients underwent limb salvage surgeries, and 66% showed good response to neoadjuvant chemotherapy. With a median follow-up period of 117 months, 31 of the evaluable 40 patients were continuously disease-free, 7 were currently alive with no evidence of disease, and 2 died of disease. There was no local recurrence. The 5-year event-free and overall survival rates were 83 and 98%, respectively. The 10-year event-free and overall survival rates were 80 and 95%, respectively. The major form of toxicity was haematological one.

Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway

“…Generally, it is considered an aggressive malignancy that arises from mesenchymal origin which exhibits osteoblastic differentiation and produces malignant osteoid matrix (2). The 10-year overall survival rate has improved to ~65% attributed to neoadjuvant chemotherapy and improved surgical techniques which nevertheless remains essentially unchanged during the past two decades (3,4). However, 10-year survival rates continue to be unsatisfactory for patients with metastatic and recurrent disease, respectively, 25% (5) and <20% (6).…”

“…Sinomenine (C 19 H 23 NO 4 , Fig. 1A), an alkaloid isolated from the Chinese medicinal herb, has been successfully utilized to treat rheumatoid arthritis for centuries (10).…”

Ifosfamide-containing Regimens for Treating Patients with Osteosarcomas

“…However, the role of ifosfamide containing combination therapy in recurrent or refractory osteosarcoma has not bee well defined, and the results differed very much. The response rate of Zhao et al was (Harris et al, 1995;Basaran et al, 2007;Zhao et al, 2010;Kudawara et al, 2013).…”

“…Some evidence suggested that a more prolonged infusion may have an improved cytotoxicity and tolerability profile although it is associated with worse urothelial toxicity compared with the three day infusion (Lorigan et al, 2007). There is clinical investigation for the use of ifosfamide in combination with other chemotherapeutic agents, eg., cisplatin, epirubicin , methotrexate etc (Harris et al, 1995;Basaran et al, 2007;Zhao et al, 2010;Kudawara et al, 2013). However, the role of ifosfamide containing combination therapy in recurrent or refractory osteosarcoma has not bee well defined, and the results differed very much.…”

Clinicopathologic Features and Prognosis of Osteosarcoma in Turkish Adults

“…But 80-90% of patients treated with only surgery develop metastasis. With the use of preoperative and postoperative chemotherapy it is possible to achive cure in two-thirds of patients (Kudawara et al, 2013). In metastatic patients the choice of treatment is chemotherapy.…”