Cyclophosphamide (Cytoxan)

Indications

Hematologic Malignances
Breast Cancer (see Breast Cancer, [[Breast Cancer]])
Wegener’s Granulomatosis (see Wegener’s Granulomatosis, [[Wegeners Granulomatosis]])

PO: 2 mg/kg/day
IV
- Rapid Induction (particularly vasculitis): 2-4 mg/kg/day x 3-4 days
- Pulsed Therapy: 15 mg/kg monthly x 1-6 months
Monitor
- CBC
- LFT’s
- Urinalysis: monitor for hematuria

Incidence of Pulmonary Toxicity: approximately 1%
- In 1996 Mayo clinic series, only 6 cases were identified where cyclophosphamide was the only identifiable etiology of lung toxicity

Epidemiology
- Typically early onset: within first 1-6 mo after start of cyclophosphamide
Diagnosis
- Open/VATS Lung Biopsy: non-specific interstitial pneumonitis
Clinical
- Cough
- Dyspnea
- Fever
- Fatigue
Treatment
- Withdraw Cyclophosphamide +/- Corticosteroids (see Corticosteroids, [[Corticosteroids]]): usually results in good clinical response
- Rechallenge: may be seen without signs of pulmonary toxicity in some cases with previous documented pulmonary toxicity

Epidemiology
- Onset of symptoms begins anywhere from 3 weeks to several years after therapy
- Pulmonary toxicity may be related to oxygen therapy and concomitant bleomcin, busulfan, or carmustine (typically prior to bone marrow transplant)
- Pulmonary toxicity is related to cyclophosphamide dose
Diagnosis
- CXR/Chest CT: interstitial reticulo-nodular infiltrates with lower-lobe predominance + pleural thickening
Clinical
- Cough
- Dyspnea
- Fever
Treatment/Prognosis
- Withdraw Cyclophosphamide + Corticosteroids (see Corticosteroids, [[Corticosteroids]]): minimal response

Lung toxicity associated with cyclophosphamide use. Two distinct patterns. Am. J. Respir. Crit. Care Med., Vol 154, No. 6, Dec 1996, 1851-1856
Interstitial pneumonitis in acute leukemia patients submitted to T-depleted matched and mismatched bone marrow transplantation. Int J Radiat Oncol Biol Phys 1998; 41: 651-657
Alveolar cells in cyclophosphamide-induced lung injury. II. Pathogenesis of experimental endogenous lipid pneumonia. Histol Histopathol 1999; 14: 1145-1152
Pulmonary toxicity of induction chemotherapy prior to standard or high-dose chemotherapy with autologous hematopoietic support. 2000; 161: 17-25
Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics 2000; 5: 1245-1259
Mileshkin L, Prince H M, Rischin D, Zimet A. Severe interstitial pneumonitis following high-dose cyclophosphamide, thiotepa and docetaxel: two case reports and a review of the literature. Bone Marrow Transplantation 2001; 27: 559-563
Segura A, Yuste A, Cercos A, al. e. Pulmonary fibrosis induced by cyclophosphamide. Annals of Pharmacotherapy 2001; 35: 894-897