Intra-arterial Cisplatin Plus Rh-endostatin Combined With Systematic Chemotherapy in Osteosarcoma

Osteosarcoma (OS) is the most common bone cancer in children and young adolescents. Despite the emergence of new therapeutic modalities such as targeted therapy and immunotherapy, chemotherapy remains the standard treatment. The current standard treatment for osteosarcoma is the preoperative chemotherapy, surgery and postoperative chemotherapy. Preoperative chemotherapy (or neoadjuvant chemotherapy) and neoadjuvant chemotherapeutic agents include cisplatin, adriamycin, methotrexate. The use of preoperative chemotherapy has increased the 5-year survival rate from 20% to 60%-70%. Over the past 40 years, limited progress has been made in improving survival outcomes in patients with OS.

Transcatheter arterial infusion (TAI) is the direct infusion of drugs in the tumor blood supply artery, which can overcome the physiological barrier that some intravenous drug can not pass, thus significantly increasing the local drug concentration in the tumor and improving the therapeutic efficacy. Studies have shown that the combination of intravenous doxorubicin and intra-arterial cisplatin infusion before surgery resulted in a favorable histological response in 87% of enrolled patients, with a 10-year survival rate of 93% and an event-free survival rate of 86%.

Recombinant endostatin, an anti-angiogenic drug approved by the National Medical Products Administration of China in 2005 for the treatment of non-small cell lung cancer. In preclinical studies, synergistic antitumor efficacy was observed in an osteosarcoma mouse model with the addition of rh-endostatin to doxorubicin. In the clinical study of osteosarcoma, after comparing 58 patients with stage IIB osteosarcoma treated with chemotherapy combined with endostatin and 272 patients treated with chemotherapy alone, results show that the 5-year DMFS (distant metastasis-free survival) of the control group (61%) was significantly lower than that of the rh-endostatin group (79%) (P = 0.013). The 5-year OS of the control group (74%) was significantly lower than that of the rh-endostatin treatment group (87%) (P = 0.029). These results suggest that endostatin combined with chemotherapy for osteosarcoma significantly improves distant metastasis-free survival, with tolerable adverse effects, and is worthy of further clinical investigation.

Therefore, the investigators propose that arterial infusion of endostatin and cisplatin combined with systematic therapy might improve the treatment efficacy in preoperative course.

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of osteosarcoma patients aged 12-40 years old;
• Accept to receive treatment with neoadjuvant chemotherapy regimen and completing the standard treatment course; Voluntary informed consent, joining the study with good compliance.
• Have detailed medical data (such as medical history data, laboratory reports of blood routine and liver and kidney functions, pathology reports, etc.), and complete records of postoperative follow-up.

Exclusion criteria

• Combined history of acute injury, infection and surgery in the last 3 months;
• Those with severe liver and kidney function abnormalities;
• Those who are using anti-inflammatory drugs;
• Pre-existing hematologic diseases before treatment;
• Combined with other malignant tumors;
• Diagnosed with autoimmune disease or using steroid drugs for more than 1 month before treatment;
• Suffering from mental illness or cognitive dysfunction.