Osteogenic Sarcoma Treatment Protocols 

Updated: Feb 10, 2016
  • Author: Edwin Choy, MD, PhD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Treatment Protocols

Treatment protocols for osteogenic sarcoma are provided below, including general and first-line treatment recommendations and recommendations for second-line therapy for relapsed or refractory disease.

General treatment recommendations for patients with osteosarcoma

Stages IA-IB (low grade):

  • Primary treatment for patients with low-grade osteogenic sarcoma includes wide excision only. Chemotherapy, either prior to excision or postoperatively, is not typically recommended [1, 2]

Stages IIA-IVB (high grade):

  • Chemotherapy is warranted for all stages of high-grade osteogenic sarcomas
  • For nonmetastatic osteosarcoma, 2-3 cycles of chemotherapy are typically given preoperatively; 3-4 cycles of chemotherapy are given postoperatively [1, 2]

First-line treatment recommendations

First-line treatment consists of any one of the regimens listed below, including the following [3, 4, 5] :

  • Doxorubicin and cisplatin
  • High-dose methotrexate, cisplatin, and doxorubicin (MAP)
  • Ifosfamide and etoposide
  • Ifosfamide, cisplatin, and epirubicin

Primary, neoadjuvant, or adjuvant therapy for metastatic disease:

Doxorubicin and cisplatin therapy:

  • Doxorubicin 75 mg/m 2 IV, divided over 1-3 d, plus  cisplatin 100 mg/m 2 IV on day 1; repeat cycle every 21d [1, 6, 7, 8]

MAP:

  • Neoadjuvant setting: High-dose methotrexate 8-12 g/m 2 IV given over 4h on weeks 0, 1, 5, 6, 13, 14, 18, 19, 23, 24, 37, and 38, alternating with cisplatin 60 mg/m 2 IV plus   doxorubicin 37.5 mg/m 2/day IV for 2 d each on weeks 2, 7, 25, and 28 [9]
  • Adjuvant setting: High-dose methotrexate 8-12 g/m 2 IV given over 4h on weeks 3, 4, 8, 9, 13, 14, 18, 19, 23, 24, 37, and 38, alternating with cisplatin 60 mg/m 2 IV plus  doxorubicin 37.5 mg/m 2/day IV for 2 d each on weeks 5, 10, 25, and 28 [9] ; two cycles are given preoperatively, and four cycles are usually given postoperatively
  • Requires administration of 15 mg leucovorin every 6 h for 12 doses, starting 24 h after initiation of high-dose methotrexate
  • If methotrexate elimination is delayed, immediately administer 150 mg IV leucovorin every 3 h until serum methotrexate levels are undetectable

Ifosfamide and etoposide:

  • Ifosfamide 9 g/m 2 over 5 d plus  etoposide 100 mg/m 2 given daily for 5 d [10]

Ifosfamide, cisplatin, and epirubicin:

  • Epirubicin 90 mg/m 2 plus  cisplatin 100 mg/m 2 on day 1 plus  ifosfamide 2 g/m 2/day plus  an equivalent dose of mesna on days 2-4, repeated every 21 d; administer six cycles (three cycles prior to surgery and three cycles postoperatively) [11]

Second-line therapy for relapsed or refractory disease

Patients with localized and metastatic osteosarcoma may relapse.

Treatment recommendations for patients with relapsed or refractory disease consist of any one of the following regimens:

  • Docetaxel and gemcitabine
  • Cyclophosphamide and etoposide
  • Cyclophosphamide and topotecan
  • Gemcitabine
  • Ifosfamide and etoposide
  • Ifosfamide, carboplatin, and etoposide
  • High-dose methotrexate, etoposide, and ifosfamide
  • Samarium-153–ethylene diamine tetramethylene phosphonate

Docetaxel and gemcitabine [12] :

Cyclophosphamide and etoposide [13] :

  • Cyclophosphamide 500 mg/m 2/day for 5d plus
  • Etoposide 100 mg/m 2/day for 5 d given with G-CSF

Cyclophosphamide and topotecan [14] :

  • Cyclophosphamide 250 mg/m 2 per dose followed by topotecan 0.75 mg/m 2 per dose, each given as a 30-min infusion daily for 5 d plus
  • Granulocyte colony-stimulating factor (G-CSF) support beginning >24 h after completion of chemotherapy

Gemcitabine [15] :

  • Gemcitabine 1000 mg/m 2 weekly for 7 wk followed by 1 wk of rest; then weekly for 3 wk out of every 4 wk

Ifosfamide and etoposide [16] :

  • Etoposide 100 mg/m 2 plus
  • Ifosfamide 3.5 g/m 2 for 5 d plus
  • G-CSF beginning >24 h after completion of chemotherapy

Ifosfamide, carboplatin, and etoposide [17] :

  • Ifosfamide 1.8 g/m 2/day plus
  • Carboplatin 400 mg/m 2/day plus
  • Etoposide 100 mg/m 2/day on days 1-3

High-dose methotrexate, etoposide, and ifosfamide [18] :

  • Ifosfamide 2.5 g/m 2 daily plus
  • Etoposide 150 mg/m 2 daily concurrently for 3 d plus
  • High-dose methotrexate 8-12 g/m 2 (with folinic acid rescue) on days 10-14 in a planned 21-d cycle

Samarium-153-ethylene diamine tetramethylene phosphonate (153 Sm-EDTMP) [19] :

  • 153 Sm-EDTMP is used for relapsed or refractory disease beyond second-line therapy (escalating doses up to 30 mCi/kg)

Special considerations

See the list below:

  • For localized, low-grade osteosarcomas, wide excision alone is typically sufficient to provide excellent overall prognosis
  • For localized, unresectable osteosarcomas, chemotherapy with radiation therapy can occasionally provide long-term, local control
  • For localized, resectable osteosarcomas, radiation therapy is used as adjuvant therapy only when there is microscopic or gross residual disease
  • Select patients with impending risk of pathologic fracture or comorbidities leading to high risk of toxicities from chemotherapy may benefit from immediate surgery
  • For high-grade sarcomas, giving chemotherapy preoperatively can offer prognostic information when the resected specimen is analyzed for degree of histologic necrosis. After 2 cycles of neoadjuvant MAP chemotherapy, if the resected specimen demonstrates necrosis <90%, prognosis is significantly poorer than if necrosis is >90% [20]
  • It is unclear if postoperative chemotherapy should be changed for poor responders or if MAP chemotherapy should be continued for another four cycles
  • For patients with particularly poor pathologic response to chemotherapy, ifosfamide and etoposide has been added to the postoperative chemotherapy regimen