How is chemotherapy dosing determined for a patient with cancer?

Chemotherapy Dosing Determination

Primary Dosing Method

Chemotherapy is dosed using actual body weight to calculate body surface area (BSA), with doses typically expressed as mg/m² of BSA, and this approach should be used for all patients including those who are obese or morbidly obese. 1

Standard Dosing Algorithm

Step 1: Calculate Body Surface Area

• Use actual body weight (not ideal or adjusted body weight) to calculate BSA 1
• Multiple BSA formulas exist (Mosteller, DuBois, etc.), though they may differ by ≥10% at extremes of weight/height 1
• Critical pitfall: Do not cap BSA at 2.0 m² or use ideal body weight for standard cytotoxic chemotherapy, as this results in underdosing and compromises efficacy 1, 2

Step 2: Apply the Standard Dose

• Multiply the drug's standard dose (mg/m²) by the calculated BSA 3
• For oral chemotherapy: use the same actual body weight-based approach as IV formulations 1
• Typical oral dosing ranges from 1-5 mg/kg daily for drugs like cyclophosphamide 4

Step 3: Adjust for Specific Agents with Fixed Dosing

Only these select agents use fixed or alternative dosing 1:

• Carboplatin: Dose using Calvert formula based on GFR (total dose [mg] = AUC × [GFR + 25]), with GFR capped at 125 mL/min and maximum dose not exceeding AUC × 150 mL/min 1
• Vincristine: Cap at 2 mg maximum when used in CHOP or CVP regimens due to neurotoxicity concerns 1
• Bleomycin: Fixed dose in BEP regimen for testicular cancer 1

Special Population Considerations

Obese Patients (BMI ≥30 kg/m²)

• Use full actual body weight for BSA calculation 1, 2
• Evidence shows no increase in toxicity with full weight-based dosing 1
• Febrile neutropenia risk actually decreases as BMI increases with proper dosing 2
• Dose reduction in obese patients compromises disease-free survival and overall survival, particularly in curative settings 1

Morbidly Obese Patients (BMI ≥40 kg/m²)

• Continue using actual body weight 1
• Apply same principles as for obese patients, with appropriate consideration of comorbidities 1

Underweight Patients

• Use actual body weight for BSA calculation 5
• 95% of oncologists routinely use actual weight in this population 5

Dose Modification for Toxicity

Managing Treatment-Related Toxicity

• Respond to toxicity identically in obese and non-obese patients 1
• Reduce doses for Grade 3-4 toxicity (neutrophils <1,500/mm³, platelets <50,000/mm³, hemoglobin <8 g/dL) 1, 4
• After toxicity resolves, resume full weight-based doses if the cause of toxicity has been corrected (e.g., improved renal function, normalized bilirubin, improved performance status) 1
• Obesity status alone should never influence dose modification decisions 1

When to Hold or Reduce Doses

• Hold treatment if neutrophils ≤1,500/mm³ and platelets <50,000/mm³ 4
• Reduce doses based on antitumor activity, myelosuppression severity, or other severe adverse reactions 4
• Consider G-CSF prophylaxis rather than dose reduction to maintain dose intensity 1, 4

Factors That Should NOT Alter Standard Dosing

Do not adjust doses based on 1:

• Obesity status alone
• Arbitrary BSA caps (e.g., 2.0 m²)
• Drug procurement costs or vial sizes
• Ideal body weight calculations (except for select non-chemotherapy agents)

Factors Requiring Dose Adjustment

Adjust doses for 1, 4:

• Patient performance status and goals of therapy 1
• Organ dysfunction (renal, hepatic impairment) 1
• Severe myelosuppression or documented toxicity 1, 4
• Combination regimens where multiple agents may require coordinated reductions 4

Maintaining Dose Intensity

• Relative dose intensity (RDI) <85% of standard is associated with worse outcomes in curative settings 1
• Approximately 50% of patients in community practice receive suboptimal RDI, primarily due to unplanned dose reductions from myelosuppression 1
• Maintaining dose intensity is crucial for survival in chemosensitive cancers like early-stage breast cancer 1

Emerging Approaches (Not Yet Standard Practice)

• Pharmacokinetic-guided dosing to target specific drug exposures (AUC) remains investigational 1, 6, 7
• Pharmacogenetic factors may inform future dosing strategies but lack sufficient evidence for routine use 1
• Therapeutic drug monitoring shows promise but is not currently standard for most cytotoxic agents 7, 8