What is the most appropriate chemotherapy agent for a 68‑year‑old woman with cervical cancer who is recovering from acute renal failure?

Optimal Chemotherapy for Cervical Cancer with Resolving Acute Renal Failure

For a 68-year-old woman with cervical cancer recovering from acute renal failure, carboplatin plus paclitaxel is the most appropriate chemotherapy regimen, as carboplatin preserves renal function while maintaining comparable efficacy to cisplatin-based therapy. 1

Primary Recommendation: Carboplatin/Paclitaxel

Carboplatin plus paclitaxel should be the first-line regimen in this clinical scenario because:

• Renal preservation is critical: Many clinicians prefer carboplatin over cisplatin specifically for ease of administration, tolerability, and preservation of renal function 1
• Comparable efficacy: The JCOG0505 phase III trial demonstrated non-inferiority of carboplatin/paclitaxel versus cisplatin/paclitaxel (median OS 17.5 vs 18.3 months; HR 0.994; 90% CI 0.79-1.25) 2
• Acceptable toxicity profile: Carboplatin/paclitaxel produces primarily hematologic toxicity rather than nephrotoxicity, with no incidence of renal toxicity reported in clinical studies 3, 4

Why Cisplatin-Based Regimens Are Contraindicated

While cisplatin/paclitaxel shows superior trends in progression-free survival and overall survival (12.9 vs 10 months) compared to other regimens 1, cisplatin is absolutely contraindicated in patients with compromised renal function:

• Cisplatin requires adequate renal function for safe administration 5
• The ability to express chemosensitivity may be modified by inadequate renal function 5
• Carboplatin is specifically recommended for patients with renal insufficiency or concern for nephrotoxicity 6

Clinical Evidence Supporting Carboplatin/Paclitaxel

Efficacy Data

• Overall response rate: 48.5% for carboplatin-based vs 49.3% for cisplatin-based chemotherapy (essentially equivalent) 4
• Median overall survival: Retrospective studies show 21 months in one cohort and 13 months in another 1
• Complete response rate: 26.7% with 60% overall clinical response rate in recurrent/persistent disease 3

Toxicity Profile

• Primary toxicity is hematologic: Grade 3-4 neutropenia occurs in 26.7% of patients 3
• No nephrotoxicity: Zero incidence of renal toxicity reported 3
• Manageable neuropathy: Grade 2-3 neuropathy in 26.7% of patients (less than cisplatin) 3
• Longer non-hospitalization periods: Significantly better quality of life compared to cisplatin regimens 2

Alternative Consideration: Gemcitabine-Based Chemoradiation

If the patient requires concurrent chemoradiation rather than systemic chemotherapy for metastatic disease, gemcitabine at 300 mg/m² weekly with pelvic radiotherapy is an acceptable alternative specifically validated in patients with renal dysfunction:

• All patients with pre-treatment creatinine ranging from 1.6 to 18.5 mg/100 mL showed improvement in creatinine clearance (pre-therapy 22.78 vs post-therapy 54.3 mg/ml/min; p=0.0058) 7
• 89% achieved complete response with this regimen 7
• Ureteral obstruction causing any degree of renal insufficiency should not be a contraindication to receive chemoradiation when gemcitabine is used instead of cisplatin 7

Critical Pitfalls to Avoid

• Do not use cisplatin in resolving acute renal failure: Even if renal function is improving, the nephrotoxic risk outweighs any potential efficacy benefit 5, 7
• Do not delay treatment waiting for complete renal recovery: Carboplatin/paclitaxel can be safely initiated with compromised renal function 1, 3
• Do not assume carboplatin is inferior: The systematic review demonstrates equivalent response rates (48.5% vs 49.3%) and acceptable survival outcomes 4
• Monitor hematologic toxicity closely: Grade 3-4 neutropenia is the primary concern, not renal toxicity 3

Practical Dosing Algorithm

Standard carboplatin/paclitaxel regimen:

• Paclitaxel 175 mg/m² over 3 hours on day 1
• Carboplatin AUC 5 mg/mL/min on day 1
• Repeat every 3 weeks 2

Monitoring requirements:

• Weekly CBC to assess for neutropenia 3
• Serial creatinine monitoring to ensure continued renal recovery 7
• Neuropathy assessment at each cycle 3

Nuance Regarding Prior Platinum Exposure

The JCOG0505 trial revealed an important caveat: among patients who had not received prior cisplatin, overall survival was shorter with carboplatin/paclitaxel (13.0 vs 23.2 months; HR 1.571) 2. However, this finding is not applicable to your patient because:

• The survival disadvantage only applies to platinum-naïve patients with normal renal function 2
• Your patient's resolving acute renal failure makes cisplatin contraindicated regardless of prior platinum exposure 5, 7
• The ESMO guidelines explicitly state carboplatin/paclitaxel is more attractive from the toxicity standpoint and should be used when cisplatin is not tolerated 1