Doxorubicin and Cisplatin Dosing for Metastatic Osteosarcoma
For metastatic osteosarcoma, use doxorubicin 25 mg/m² on days 1-3 and cisplatin 100 mg/m² on day 1, repeated every 3 weeks for 6 cycles (18 weeks total). 1
Standard Dosing Regimen
The two-drug combination of doxorubicin and cisplatin is a well-established standard regimen that has demonstrated comparable efficacy to more complex multi-drug protocols while offering superior tolerability 2, 1.
Specific Dosing Schedule:
- Doxorubicin: 25 mg/m² IV on days 1,2, and 3 of each cycle 1
- Cisplatin: 100 mg/m² IV on day 1 of each cycle 1
- Cycle length: 21 days (3 weeks) 1
- Total duration: 6 cycles = 18 weeks 1
This regimen achieved 94% completion rates compared to only 51% for multi-drug regimens, with equivalent 5-year survival of 55% 1.
Alternative Dosing Considerations
Higher Intensity Regimens
For patients requiring more aggressive therapy, alternative dosing includes:
- Doxorubicin: 75 mg/m² as a single dose (preoperatively) or 90 mg/m² (postoperatively) 3, 4
- Cisplatin: 100-120 mg/m² as a single dose 3, 4
However, the standard 3-day doxorubicin schedule remains preferred for metastatic disease due to better tolerability 1.
Pegylated Liposomal Doxorubicin
For patients with prior doxorubicin exposure or cardiac concerns:
- PEG-LD: 50 mg/m² on day 1 (maximum tolerated dose) 5
- Cisplatin: 100 mg/m² on day 1 5
- This formulation reduces cardiac toxicity while maintaining efficacy 5
Critical Management Points
Supportive Care Requirements
- G-CSF prophylaxis: Essential to manage neutropenia, particularly with higher-intensity regimens 3
- Hydration: Rigorous IV hydration required for cisplatin administration 2
- Antiemetics: Aggressive prophylaxis needed for both agents 1
Toxicity Monitoring
- Hematologic: Expect grade 3-4 neutropenia, thrombocytopenia requiring close monitoring 3, 5
- Cardiac: Monitor cumulative doxorubicin dose to minimize cardiotoxicity 4
- Renal: Monitor creatinine clearance with cisplatin; dose adjustments may be needed 5
Treatment Duration and Surgery
Even with metastatic disease, aggressive surgical resection of all disease sites should be pursued if feasible after chemotherapy response 6. Approximately 30% of patients with metastatic osteosarcoma become long-term survivors if complete surgical resection is achieved 6. Without surgery, the disease is almost universally fatal despite chemotherapy 6.
Timing of Surgery
- Surgery typically scheduled at week 9 for the two-drug regimen 1
- Continue same chemotherapy regimen postoperatively 2
Common Pitfalls to Avoid
- Do not abandon curative intent: Even single metastases warrant aggressive treatment including surgery 2, 6
- Do not underdose: The 3-day doxorubicin schedule (75 mg/m² total per cycle) is critical for efficacy 1
- Do not delay cycles unnecessarily: Dose intensity matters; 89% of planned dose intensity was achieved in successful protocols 3
- Do not use cisplatin alone: The combination is superior to single-agent therapy for metastatic disease 7