OGS-12 Chemotherapy Regimen Dosing and Schedule
The OGS-12 protocol consists of 8 cycles total (4 neoadjuvant, 4 adjuvant) using sequential doublets of doxorubicin 25 mg/m² days 1-3 plus cisplatin 100 mg/m² day 1, alternating with ifosfamide-based doublets, delivered over approximately 32-36 weeks. 1, 2
Detailed Dosing Schedule
Neoadjuvant Phase (4 cycles before surgery)
- Cycle 1 & 3: Doxorubicin 25 mg/m² IV on days 1-3 + Cisplatin 100 mg/m² IV on day 1 1, 2
- Cycle 2 & 4: Ifosfamide (specific dose not detailed in evidence, but part of sequential doublet strategy) 1, 2
- Surgery is scheduled after completion of 4 neoadjuvant cycles 1, 2
Adjuvant Phase (4 cycles after surgery)
- Same sequential doublet pattern repeated for 4 additional cycles using doxorubicin/cisplatin alternating with ifosfamide 1, 2
- Total treatment duration: approximately 32-36 weeks for all 8 cycles 2
Key Advantages Over Standard Regimens
- No high-dose methotrexate required, eliminating the need for mandatory inpatient pharmacokinetic monitoring, leucovorin rescue protocols, potential dialysis support, and complex serum level measurements 3, 2
- Dose-dense delivery with better completion rates: 94% of patients completed all 6 cycles in comparable two-drug regimens versus only 51% completing multi-drug protocols 4
- Outpatient administration feasible for most cycles, making it particularly suitable for resource-limited settings 2
Supportive Care Requirements
- Rigorous IV hydration mandatory with cisplatin administration 5
- Mesna required with ifosfamide to prevent hemorrhagic cystitis 6
- Growth factor support should be considered given high rates of febrile neutropenia (51-56%) 1, 2
- Antiemetic prophylaxis essential, particularly with cisplatin 4
Expected Outcomes
- Histologic good response rate: 58-59% in non-metastatic disease, 56-57% in metastatic disease (defined as ≤10% viable tumor cells) 1, 2
- 5-year survival in non-metastatic disease: Event-free survival 56-60%, overall survival 75-80% 2
- 4-year survival in metastatic disease: Event-free survival 24-27%, overall survival 27-29% 1
- These outcomes are comparable to international standards achieved with high-dose methotrexate-based MAP regimens 1, 2
Critical Toxicity Profile
- Hematologic toxicity (most common): Febrile neutropenia 51-56%, grade 3/4 thrombocytopenia 22-36%, grade 3/4 anemia 47-54% 1, 2
- Gastrointestinal toxicity: Grade 3/4 diarrhea and stomatitis in approximately 10% 2
- Renal toxicity: Rare but serious; one case of grade 4 acute kidney injury requiring dialysis reported 2
- Chemotherapy-related mortality: Approximately 1% (2 deaths in 317 patients) 2
Essential Clinical Pitfalls to Avoid
- Surgery remains mandatory for cure: Without complete surgical resection of primary tumor and metastases, disease is almost universally fatal despite chemotherapy 7, 5
- Aggressive metastasectomy should be pursued even with single metastases after chemotherapy response, as approximately 30% of metastatic patients achieve long-term survival with complete resection 7, 3
- Histologic response is the strongest predictor of event-free and overall survival in both metastatic and non-metastatic disease 1, 2
- Nutritional optimization is critical as 34% of patients in the original cohort were nutritionally challenged at baseline 2