Intraperitoneal (IP) Chemotherapy Regimen
For optimally debulked stage III epithelial ovarian cancer, the recommended IP chemotherapy regimen is: paclitaxel 135 mg/m² IV continuous infusion over 24 hours on day 1, followed by cisplatin 75-100 mg/m² IP on day 2, and paclitaxel 60 mg/m² IP on day 8, repeated every 3 weeks for 6 cycles. 1
Patient Selection Criteria
This regimen is specifically indicated for:
- Stage III epithelial ovarian cancer with optimal debulking (<1 cm residual disease) 1
- Stage II disease may also be considered, though randomized evidence is lacking 1
- High-grade serous, grade 2/3 endometrioid, and clear cell carcinoma 1
Required Patient Characteristics Before Starting
Patients must meet ALL of the following criteria 1:
- Normal renal function at baseline
- Medically appropriate performance status to tolerate increased toxicity
- No pre-existing neuropathy
- No medical conditions that could significantly worsen during treatment
Detailed Dosing Schedule
The complete regimen per 21-day cycle: 1
- Day 1: Paclitaxel 135 mg/m² IV continuous infusion over 24 hours (or 3 hours per some protocols)
- Day 2: Cisplatin 75-100 mg/m² IP (after IV paclitaxel completion)
- Day 8: Paclitaxel 60 mg/m² IP (maximum body surface area 2.0 m²)
- Total cycles: 6 cycles
Cisplatin Dosing Considerations
Use the lower cisplatin dose of 75 mg/m² to decrease toxicity 1. The GOG-0252 trial used 75 mg/m² (versus 100 mg/m² in GOG-172), though this lower dose did not demonstrate improved outcomes compared to IV therapy 1. However, the 75 mg/m² dose may improve tolerability while maintaining the Category 1 recommendation 1.
Survival Benefit
This IP regimen demonstrated a 16-month overall survival advantage over standard IV therapy (65.6 vs 49.7 months; P = .03) in the GOG-172 trial 1. This represents a Category 1 recommendation based on randomized controlled trial evidence 1.
Toxicity Profile and Management
Expected Toxicities
The IP paclitaxel/cisplatin regimen is associated with 1:
- Leukopenia and infection
- Fatigue
- Renal toxicity
- Abdominal discomfort and pain
- Neurotoxicity
- Nausea/vomiting/dehydration
- Catheter complications
Critical Management Strategies
Aggressive hydration is mandatory to prevent renal toxicity: 1
- Administer IV hydration BEFORE each IP cisplatin dose
- Administer IV hydration AFTER each IP cisplatin dose
- Patients often require outpatient IV fluids for 5-7 days after each cycle
- Monitor carefully for dehydration, electrolyte loss, and end-organ toxicities 1
Completion Rates and Dose Modifications
Only 42% of patients completed all 6 cycles in initial studies due to toxicity 1. However, completion rates have improved at major cancer centers with experience 1.
Common reasons for discontinuation: 1
- Catheter complications
- Abdominal pain
- Nausea/vomiting/dehydration
- Abdominal discomfort
If patients cannot complete IP therapy, switch to IV chemotherapy 1. The standard IV alternative is paclitaxel 175 mg/m² IV over 3 hours followed by carboplatin AUC 5-7.5 IV every 3 weeks 1.
Alternative Considerations
Modified IP Regimen
A feasibility study demonstrated that administering both IV paclitaxel and IP cisplatin on day 1, followed by IP paclitaxel on day 8, is feasible with 95% of patients completing all 6 cycles 2. This modification may improve tolerability compared to the 24-hour paclitaxel infusion.
Current Guideline Status (2020-2021)
The NCCN downgraded IP chemotherapy to Category 2A ("useful in certain circumstances") in their 2020 guidelines 1, reflecting ongoing controversy about its use 1. This downgrade occurred after GOG-0252 failed to show superiority of IP chemotherapy when bevacizumab was added to both arms 1.
ESMO Perspective
ESMO guidelines consider IP therapy experimental and recommend its use only in clinical trials 1. The absence of current standard IV control arms in historical trials and greater toxicity have limited widespread adoption outside the United States 1.
Important Caveats
- Catheter choice and timing of insertion are critical to minimize complications 1
- Expert nursing care may help decrease complications 1
- The regimen requires significant institutional experience and infrastructure for optimal outcomes 1
- Whether to use IP versus IV chemotherapy remains controversial despite survival data 1