Non-methotrexate based triple drug combination chemotherapy for untreated osteosarcoma

Abstract

20512 Background: Considering the high cost of intensive high-dose methotrexate based chemotherapy, a non-methotrexate based chemotherapy regimen was evaluated in newly diagnosed osteosarcoma patients Methods: A total of 54 patients of newly diagnosed osteosarcoma (2000 to 2005) were included in the study. Chemotherapy protocol included 3 drugs viz. Doxorubicin (20 mg/m2 on Day1 to Day3), Cisplatin (100 mg/m2 on Day 1) and Ifosfamide (2000 mg/m2 on Day1 to Day 5) in combination as A1 cycle - Ifosfamide + Doxorubicin, B1 cycle - Doxorubicin + Cisplatin, C1 cycle - Cisplatin + Ifosfamide. The sequence was repeated as A2, B2 and C2 (total 6 cycles). Surgical excision of primary tumor was done after 3 cycles of chemotherapy Results: The median age at diagnosis was 15.5 years with a slight male preponderance (n=38, 70.4 %). Axial skeleton (maxillary) was affected only in one patient. Lower end of femur was the most common appendicular skeletal site for the primary tumor (n=27, 50 %). Forty two out of 54 (77.8 %) patients had nonmetastatic disease at diagnosis. Lung was the most common site of distant metastasis at diagnosis (11 out of 12 patients). Fifty patients received all 6 chemotherapy cycles as planned. Limb salvage with reconstruction surgery was performed in 35 (64.8 %) patients. Complete (100%) tumor necrosis was seen in 18 (33.3 %) patients. The median duration of follow-up was 16 months. The actuarial disease free and overall survival at 3 years would be 41.4 % and 43.6 % respectively. The incidence of febrile neutropenia was 11.85 % and of grade III/IV thrombocytopenia was 10 % of all chemotherapy cycles. Easily controllable emesis was the commnoest non-hematological toxicity, experienced by 31.5 % of patients. Two patients died due to post chemotherapy neutropenic sepsis. With univariate analysis, complete histological response (100 % tumor necrosis) alone could be identified as independent favorable prognostic factor (3 year OS of 73.6 %, P=0.003). The overall survival outcome was not statistically different in subgroups of sex, age group and pathological tumor size. Conclusions: Non-methotrexate based triple drug combination chemotherapy is an effective treatment option for patients with newly diagnosed osteosarcoma in developing countries like India. No significant financial relationships to disclose.

Osteosarcoma journey over two decades in India: Small steps, big changes

“…Cumulative doses of each drug were Dox 240 mg /m 2 , CDDP 400 mg/m 2 , and Ifo 40 g/m 2 . This protocol did not mandate primary granulocyte colony stimulating factor (G‐CSF) support as the cost was a limiting factor in its uniform implementation (Figure ) …”

“…However, the results of the older protocols were suboptimal, with higher toxicity, dose reductions, and delays. 5 Hence, we worked on a step-wise approach and devised a dosedense and intense chemotherapy protocol based on tumor kinetic principles, 6,7 eliminating ineffective drugs based on emerging evidence and intensified supportive care to improve compliance. This perspective describes the journey of osteosarcoma care over a span of two decades, wherein we used three sequential non-HDMTXbased combination chemotherapy protocols at a single tertiary care center in India, in nonmetastatic osteosarcoma patients.…”

“…To circumvent these impediments, various non‐HDMTX‐based protocols have been used since long in LMICs, including at our center. However, the results of the older protocols were suboptimal, with higher toxicity, dose reductions, and delays . Hence, we worked on a step‐wise approach and devised a dose‐dense and intense chemotherapy protocol based on tumor kinetic principles, eliminating ineffective drugs based on emerging evidence and intensified supportive care to improve compliance.…”