How is carboplatin dosed?

How Carboplatin is Dosed

Carboplatin should be dosed using the Calvert formula based on glomerular filtration rate (GFR) to achieve a target area under the curve (AUC), with the dose calculated as: Total Dose (mg) = target AUC × (GFR + 25). 1, 2, 3

The Calvert Formula: Standard Dosing Method

• The Calvert formula calculates the total dose in milligrams (mg), NOT mg/m², which is a critical distinction from traditional body surface area-based chemotherapy dosing 1, 2
• The formula has been prospectively validated to accurately predict carboplatin exposure across a wide range of renal function (GFR 33-136 mL/min) 1, 3
• The American Society of Clinical Oncology recommends this formula as the standard approach to prevent underdosing in patients with above-average renal function or overdosing in those with impaired renal function 1

Critical GFR Cap to Prevent Overdosing

• The GFR value used in the Calvert formula should NEVER exceed 125 mL/min, even if the measured GFR is higher, to prevent overdosing in patients with supranormal renal function 1
• The maximum carboplatin dose should not exceed AUC (mg·min/mL) × 150 mL/min 1

Target AUC Selection by Clinical Context

Single-Agent Carboplatin

• For previously treated patients: target AUC of 4-6 mg/mL·min (typically AUC 5) 1, 2, 3
• For previously untreated patients: target AUC of 6-8 mg/mL·min (typically AUC 7) 3
• Higher AUC values correlate with increased myelotoxicity: 16% experience grade 3-4 thrombocytopenia at AUC 4-5 versus 33% at AUC 6-7 1, 2

Combination Chemotherapy Regimens

• For carboplatin plus paclitaxel in ovarian cancer: AUC 5-7 mg/mL·min every 3 weeks for 6 cycles 4, 1
• Standard regimen: Paclitaxel 175 mg/m² IV over 3 hours followed by carboplatin AUC 5-6 IV over 1 hour on Day 1, every 3 weeks 4, 5
• Dose-dense regimen: Paclitaxel 80 mg/m² on Days 1,8,15 plus carboplatin AUC 6 on Day 1, every 3 weeks 4, 5
• Weekly regimen: Paclitaxel 60 mg/m² plus carboplatin AUC 2 weekly for 18 weeks 5

Testicular Cancer (Adjuvant Seminoma)

• One or two cycles of carboplatin AUC 7 as category 1 recommendation for stage IA and IB pure seminoma 4
• Dose calculated as: 7 × (GFR [mL/min] + 25 mg) 4

Renal Function Assessment Methods

• GFR should ideally be measured directly by ⁵¹Cr-EDTA clearance (the method used in original Calvert formula validation) 2, 3
• Alternative acceptable methods for adult Japanese patients (generalizable to other populations): 24-hour urinary creatinine clearance adjusted by adding 0.2 mg/dL to standardized serum creatinine, or equation-based GFR with back calculation to mL/min per subject 6
• Avoid using standardized serum creatinine values directly without adjustment, as this carries high risk of carboplatin overdosing 6

Special Population Considerations

Impaired Renal Function

• Patients with creatinine clearance below 60 mL/min are at increased risk of severe bone marrow suppression 2
• For creatinine clearance 41-59 mL/min: 250 mg/m² on Day 1 (if using empiric BSA dosing) 2
• For creatinine clearance 16-40 mL/min: 200 mg/m² on Day 1 (if using empiric BSA dosing) 2
• Data are too limited for patients with creatinine clearance below 15 mL/min to permit dosing recommendations 2

Elderly Patients

• Formula dosing based on GFR estimates should ALWAYS be used in elderly patients to provide predictable plasma carboplatin AUCs and minimize toxicity risk 1, 2
• Age-related decline in renal function may not be reflected in serum creatinine due to decreased muscle mass, making formula dosing essential 1

Obese Patients

• Dosing based on GFR is most reasonable because carboplatin clearance correlates with GFR, which correlates with body surface area 1

Empiric Body Surface Area Dosing (Alternative Method)

When the Calvert formula cannot be used:

Combination with Cyclophosphamide

• Carboplatin 300 mg/m² IV on Day 1 every 4 weeks for 6 cycles 2
• Cyclophosphamide 600 mg/m² IV on Day 1 every 4 weeks for 6 cycles 2

Dose Adjustments Based on Blood Counts

• If platelets >100,000 and neutrophils >2,000: increase dose to 125% of prior course 2
• If platelets 50,000-100,000 and neutrophils 500-2,000: no adjustment 2
• If platelets <50,000 and neutrophils <500: decrease dose to 75% of prior course 2

Administration Guidelines

• Standard infusion: carboplatin administered over 1 hour when given at AUC 5-6 7, 5
• Weekly regimens: carboplatin at AUC 2 administered over 30 minutes 7, 5
• No pre- or post-treatment hydration or forced diuresis is required (unlike cisplatin) 2

Critical Safety Warnings

• Patients with prior platinum exposure have 27-46% risk of hypersensitivity reactions, particularly after cycle 7 7, 5
• Monitor for hypersensitivity reactions during infusion, which occur in 1-30% of patients and typically manifest within minutes or during the infusion 7, 5
• For patients with mild hypersensitivity or anxiety, premedications and slowed infusion rates may be used without formal desensitization 7, 5

Common Pitfalls to Avoid

• Never use modified Calvert formulae with serum creatinine-based GFR estimates in combination regimens (particularly carboplatin-paclitaxel), as these can overestimate AUC by 27-33% with poor precision 8
• Do not misinterpret the Calvert formula output: the result is total dose in mg, not mg/m² 1, 9
• Do not exceed GFR cap of 125 mL/min in the formula calculation 1
• The target AUC must be adjusted for combination chemotherapy regimens, as the formula measures drug exposure, not toxicity 1