What is the typical dose of cyclophosphamide (CYC) for chemotherapy and autoimmune disease treatment?

Cyclophosphamide Dosing

Cyclophosphamide dosing varies significantly by indication: for chemotherapy, use 40-50 mg/kg IV divided over 2-5 days or 600 mg/m² every 21 days in combination regimens; for autoimmune diseases, use either oral therapy at 1-3 mg/kg/day (maximum 200 mg/day) or IV pulse therapy at 15 mg/kg (maximum 1500 mg) every 2-4 weeks with mesna protection. 1, 2

Chemotherapy Dosing

Breast Cancer Regimens

• AC regimen: Cyclophosphamide 600 mg/m² IV on day 1, cycled every 21 days for 4 cycles 3
• TAC regimen: Cyclophosphamide 500 mg/m² IV on day 1 with doxorubicin and docetaxel, cycled every 21 days for 6 cycles (requires filgrastim support) 3
• TC regimen: Cyclophosphamide 600 mg/m² IV on day 1 with docetaxel, cycled every 21 days for 4 cycles 3
• Dose-dense AC: Cyclophosphamide 600 mg/m² IV every 14 days for 4 cycles with filgrastim support 3

Monotherapy for Malignancies

• Initial course: 40-50 mg/kg IV divided over 2-5 days for patients without hematologic deficiency 2
• Alternative regimens: 10-15 mg/kg IV every 7-10 days, or 3-5 mg/kg IV twice weekly 2

Autoimmune Disease Dosing

Oral Daily Therapy

• Adults: 1-3 mg/kg/day (maximum 200 mg/day) with dose adjustments based on white blood cell counts 1
• Pediatric patients: 1.5-3 mg/kg/day 1
• Treatment failure definition: Failure to achieve disease control after 3 months at 2 mg/kg/day 3

Intravenous Pulse Therapy

• Standard dose: 15 mg/kg (maximum 1500 mg) initially every 2 weeks, then reducing to every 3 weeks for maximum 6 months 3, 1
• Alternative fixed-dose regimens: 500-1000 mg monthly 3, 1

Disease-Specific Protocols

ANCA-Associated Vasculitis:

• 15 mg/kg IV (maximum 1500 mg) initially every 2 weeks, reducing to every 3 weeks, continued for 3-6 months for remission induction 3, 1
• Dose reductions required for age and renal function: patients >70 years with creatinine >300 mmol/L receive 7.5 mg/kg/pulse 3

Pemphigus Vulgaris (DCP Regimen):

• Phase 1: 500 mg IV cyclophosphamide on day 2 of monthly cycles with dexamethasone 100 mg IV on 3 consecutive days, plus oral cyclophosphamide 50 mg daily between pulses 3
• Phase 2: Continue monthly DCP for 6-9 months consolidation 3
• Phase 3: Oral cyclophosphamide alone for 9-12 months 3
• Alternative: 15 mg/kg IV monthly combined with conventional oral corticosteroids without daily oral cyclophosphamide 3

Critical Safety Measures

Mandatory Protective Interventions

• Mesna administration: Required for all patients receiving pulse cyclophosphamide to prevent hemorrhagic cystitis (occurs in 6% without protection) 3, 1
• Hydration: Adequate fluid intake (2-3 L in 24 hours) during and after administration to force diuresis 1, 2
• Morning administration: Cyclophosphamide should be given in the morning to allow daytime voiding and reduce bladder exposure to toxic metabolites 2

Infection Prophylaxis

• Pneumocystis jirovecii prophylaxis: Trimethoprim/sulfamethoxazole 800/160 mg on alternate days or 400/80 mg daily for all patients on cyclophosphamide 1

Administration Guidelines

Intravenous Preparation

• For direct IV injection: Dilute to 20 mg/mL using 0.9% sodium chloride, 0.45% sodium chloride, 5% dextrose, or 5% dextrose with 0.9% sodium chloride 2
• For IV infusion: Dilute to 2 mg/mL using the same diluents 2
• Infusion rate: Administer very slowly to reduce rate-dependent adverse reactions (facial swelling, headache, nasal congestion, scalp burning) 2
• Do not use sterile water for direct injection as it creates a hypotonic solution 2

Storage of Diluted Solutions

• Room temperature: up to 24 hours 2
• Refrigerated: up to 6 days 2

Dose Modifications

Renal Impairment

• Dose reductions required for moderate to severe renal impairment 2
• For ANCA vasculitis with creatinine 300-500 mmol/L in patients <60 years: reduce to 12.5 mg/kg/pulse 3
• For creatinine >500 mmol/L: further reductions necessary 3

Age-Related Adjustments

• Patients 60-70 years: reduce pulse dose by approximately 20% 3
• Patients >70 years: reduce pulse dose by approximately 30-50% depending on renal function 3

Hematologic Monitoring

• Adjust dose or discontinue for acute leukopenia or gradual decline in white blood cell counts 1
• Close hematological monitoring required due to severe myelosuppression risk 2

Major Toxicities to Monitor

Gonadal Toxicity

• Amenorrhea occurs in 20-85% of menstruating women 3, 1
• Azoospermia in men 3, 1
• Risk increases with cumulative dose and age 1
• Fertility preservation should be discussed before initiating therapy 1

Urinary Tract Toxicity

• Hemorrhagic cystitis in 6% without mesna protection 3, 1
• Exclude or correct urinary tract obstructions prior to treatment 2

Other Serious Toxicities

• Secondary malignancies with long-term use 1, 2
• Cardiotoxicity including myocarditis and congestive heart failure 2
• Pulmonary toxicity including pneumonitis and pulmonary fibrosis 2
• Veno-occlusive liver disease 2

Common Pitfalls

Avoid combining cyclophosphamide with trastuzumab and anthracyclines concurrently due to cardiac toxicity, except in specific neoadjuvant protocols 3. The mortality rate with DCP therapy ranges from 2-4%, emphasizing the need for careful patient selection and monitoring 3. Reserve cyclophosphamide for severe or recalcitrant autoimmune cases given long-term toxicity concerns and practical disadvantages of regular IV treatment 3.