ADM: 45 mg/m2/day as an 8 h infusion for 2 consecutive days
MTX: as in preoperative treatment
CDP: 150 mg/m2 as a 72 h continuous infusion
IFO: 2 g/m2/day as a 1 h infusion for 5 consecutive days.
In patients with localized disease and total necrosis the last 3 cycles of chemotherapy were omitted.
Fig. 21-5. Chemotherapy regimen as per Rizzoli's 4th protocol. (From Bacci G, Briccoli A, Ferrari S, Longhi A, Mercuri M, Capanna R, Donati D, Lari S, Forni C, DePaolis M. Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol. Eur J Cancer 2001;37:2030-9, with permission.)
Methotrexate is administered in 1 L of D5W 1/4 NS with 50 mEq of sodium bicarbonate per liter over 4 hours after urine pH is over 7.0. Hydration is administered to achieve a urine output of 1400-1600 mL/m2 for the first 24 hours after methotrexate and a minimum urine output of 2000 mL/m2 for each 24-hour period after that. Sodium bicarbonate is administered to achieve a urine pH greater than 7.0. Oral leu-covorin is begun 20 hours after the completion of the methotrexate infusion at a dose of 10 mg every 6 hours continuing until the 72-hour methotrexate level (and longer if necessary) is less than 1.0 x 10-7 mol/L. Patients whose methotrexate excretion is delayed require increased dose or duration of leucovorin (Figure 21-6).
Approximately 15-20% of patients with osteosarcoma present with metastatic disease. Etoposide and high-dose ifosfamide are effective neoadjuvant chemotherapy for metastatic osteosarcoma. The following is the management approach to patients who present with metastatic disease:
1. Preoperative induction chemotherapy is used to assess the chemoresponsive-ness of the primary and metastatic lesions (Figure 21-7).
2. Surgical amputation or limb salvage surgery of the primary lesion is performed. Surgical removal of metastatic sites is recommended, if feasible.
3. Figure 21-8 depicts details of an appropriate continuation adjuvant regimen utilizing high-dose ifosfamide, etoposide, high-dose methotrexate, doxorubicin, and cisplatin (CDDP).
4. With the above-mentioned chemotherapy protocol, 2-year PFS for the patients with pulmonary metastases is 39% ± 11%. The projected 2-year PFS for the patients with bone metastases is 58% ± 17%.
5. When a tumor arises in a site that is not resectable, radiation may be used for local control, even though osteogenic sarcoma is usually not radiosensitive.
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