Cyclophosphamide (Cytoxan)

Indications


Pharmacology

  • Alkylating Agent

Administration

  • 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

Adverse Effects

Hematalogic-Oncologic Adverse Effects

Myelodysplastic Syndrome (MDS)

  • Epidemiology: occurs in 8% of cases

Solid Malignancy

  • Epidemiology: occurs in 5% of cases

Pulmonary Adverse Effects

General Comments

  • 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

Early-Onset Acute Pneumonitis (see Pneumonia, [[Pneumonia]])

  • 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

Late-Onset Pneumonitis and Interstitial Pulmonary Fibrosis (see Pneumonia, [[Pneumonia]] and Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]]

  • 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

Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])

  • Epidemiology: xxx

Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])

  • Epidemiology: xxx

Cryptogenic Organizing Pneumonia (see Cryptogenic Organizing Pneumonia, [[Cryptogenic Organizing Pneumonia]] and Lung Nodule or Mass, [[Lung Nodule or Mass]])

  • Clinical: may appear as nodular infiltrates

Other Adverse Effects

Hemorrhagic Cystitis

  • Epidemiology: occurs in 12% of cases

References

  • 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