The aim of the study is to test the feasibility of four-drug, interval-compressed regimen in osteosarcoma.

Primary objective is to explore the toxicity and mortality related to treatment. Secondary objectives are to examine tumor necrosis rates after neoadjuvant chemotherapy, and to evaluate the usefulness of circulating cell-free DNA, survivin, or transforming growth factor-beta1 levels as well as programmed cell death ligand 1 expression in tumor specimen as a predictive or prognostic biomarker in osteosarcoma patients.

In this study, the investigators will investigate the feasibility of interval compressed regimen using four-drugs in newly-diagnosed osteosarcoma patients. Four drugs will be adriamycin, high-dose methotrexate, cisplatin, ifosfamide. All these drugs will be given preoperatively in an interval-compressed schedule, but postoperatively at a regular interval. Neoadjuvant therapy will be composed of two courses, and adjuvant therapy of two or three courses depending on necrosis rates following neoadjuvant therapy.

Inclusion Criteria:

• Newly diagnosed osteosarcoma patients under age 40 years.

Exclusion Criteria:

• Patients who don't meet the organ function criteria as follows;

  1. renal function : CCr or GFR or eGFR ≥ 70 mL/min/1.73 m2
  2. liver function : AST/ALT ≤ 5 x upper limit, total bilirubin ≤ 1.5 x upper limit of normal for age
  3. cardiac function : shortening fraction ≥ 24% or ejection fraction ≥ 50% (Echo)
  4. lung function : No dyspnea on rest, If dyspnea exists, SpO2 95% or more in room air by pulse oximetry,
  5. hematologic : ANC ≥ 750/uL and platelet ≥ 75,000/uL

Clinical data of individual participants can be shared without personal information. Each participating center will submit the clinical data to the principal investigation center, after eliminating personal data.