What is the recommended neoadjuvant chemotherapy regimen for osteosarcoma?

Neoadjuvant Chemotherapy Regimen for Osteosarcoma

The recommended neoadjuvant chemotherapy regimen for osteosarcoma is MAP (high-dose methotrexate, cisplatin, and doxorubicin), which is the standard of care for patients with high-grade osteosarcoma. 1

Standard Regimens for High-Grade Osteosarcoma

• MAP (high-dose methotrexate, cisplatin, and doxorubicin) is the preferred first-line neoadjuvant chemotherapy regimen for high-grade osteosarcoma 1
• Alternative regimens include:
  • Doxorubicin and cisplatin 1
  • Doxorubicin, cisplatin, ifosfamide, and high-dose methotrexate 1
  • Ifosfamide and etoposide 1
  • Ifosfamide, cisplatin, and epirubicin 1

Dosing and Administration

• For high-dose methotrexate, the starting dose is typically 12 g/m² IV as a 4-hour infusion, which may be escalated to 15 g/m² in subsequent treatments if peak serum methotrexate concentration is insufficient 2
• Leucovorin rescue (15 mg orally every six hours for 10 doses) should be started 24 hours after beginning methotrexate infusion 2
• Doxorubicin is typically administered at 30 mg/m²/day IV for 3 days 2
• Cisplatin is typically administered at 100 mg/m² IV 2

Treatment Algorithm

1. Initial Assessment:

   • Confirm high-grade osteosarcoma diagnosis 1
   • Complete staging workup including imaging of primary site and chest 1
   • Assess baseline laboratory values including alkaline phosphatase and LDH 1

2. Neoadjuvant Chemotherapy:

   • Begin with MAP regimen for most patients with high-grade osteosarcoma 1
   • Administer 2-4 cycles before surgical resection 1, 3
   • Monitor for response using appropriate imaging modalities 1

3. Surgical Planning:

   • Reassess tumor for resectability after neoadjuvant chemotherapy 1
   • Plan for wide excision with limb-sparing surgery when possible 1

4. Post-Surgical Assessment:

   • Evaluate histologic response to neoadjuvant chemotherapy 1
   • Good response: <10% viable tumor 1
   • Poor response: ≥10% viable tumor 1

5. Adjuvant Chemotherapy:

   • Good responders: Continue with same chemotherapy regimen 1
   • Poor responders: Consider continuing with preoperative regimen or switching to a different regimen (category 3 recommendation) 1

Special Considerations

• Selected older patients may benefit from immediate surgery without neoadjuvant chemotherapy 1
• For unresectable tumors after preoperative chemotherapy, consider radiation therapy or additional chemotherapy 1
• Histologic response to neoadjuvant chemotherapy is a significant prognostic factor, with good responders having better outcomes 1, 3
• The 5-year disease-free survival rates are significantly higher for good responders (67.9%) compared to poor responders (51.3%) 1

Treatment Challenges

• Attempts to improve outcomes in poor responders by modifying adjuvant chemotherapy have been largely unsuccessful 1, 4
• Increasing doses of preoperative chemotherapy does not necessarily improve the rate of good histologic response or survival 4
• For patients with metastatic disease at presentation, outcomes are significantly worse, with 2-year event-free survival rates of only 21% compared to 75% for non-metastatic disease 5

Monitoring and Supportive Care

• Chemotherapy should include appropriate growth factor support to manage myelosuppression 1
• Regular monitoring for toxicities is essential, particularly with high-dose methotrexate 2
• Repeat imaging using pre-treatment modalities should be performed to assess tumor response 1

The evidence strongly supports the use of neoadjuvant chemotherapy followed by surgery as the standard approach for high-grade osteosarcoma, with MAP being the preferred regimen based on the most recent NCCN guidelines 1.