Cyclophosphamide
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Interstitial pneumonitis: case report A 59-year-old woman with breast cancer developed interstitial pneumonitis during chemotherapy with cyclophosphamide. The woman underwent modified radical mastectomy and tangential radiotherapy, and then received three courses of chemotherapy with cyclophosphamide 800mg and doxorubicin (12 December 2007, 9 January 2008, 30 January 2008). She developed dyspnoea, cough and fever on 13 February 2008. On presentation 1 week later, interstitial shadows were evident on x-ray and she was hospitalised. She had a BP of 93/55mm Hg and a pulse rate of 97/min. A chest x-ray revealed predominantly central ground glass opacities in both lungs, and a CT scan also identified a panlobular distribution. Laboratory investigations showed the following: WBC count 5200/mm3 with 7.1% lymphocytes, RBC count 312 × 104/mm3, haemoglobin 9.4 g/dL, platelet count 59.2 × 104/mm3, LDH 382 IU/L, CRP 1.9 mg/dL. Drug lymphocyte stimulation tests were negative for cyclophosphamide and doxorubicin. Arterial blood gas analysis disclosed mild hypoxaemia (pO2 68.3Torr). A slightly increased lymphocyte and neutrophil count, as well as an elevated CD4/CD8 count was identified in bronchoalveolar lavage fluid. A lung biopsy disclosed no significant findings. The woman received methylprednisolone pulse therapy followed by prednisolone, cotrimoxazole [trimethoprim/ sulfamethoxazole] and ganciclovir. Her symptoms, imaging findings and arterial blood gas values rapidly improved. Cotrimoxazole and ganciclovir were withdrawn after 2 weeks, and prednisolone was gradually withdrawn on 18 March; at that time, her PaO2 had normalised. The woman was rechallenged with IV cyclophosphamide 100mg; 100mg increases up to her therapeutic 800mg dose were scheduled. She was asymptomatic after the first 100mg infusion, and test results were negative; however, her PaO2 had decreased to 72.6Torr after 24 hours, and recovered to 83.0Torr after 48 hours. Additionally, her eosinophil counts transiently increased during the same time, but her general condition remained unchanged. Drug-induced lung injury secondary to cyclophosphamide was diagnosed. Author comment: In the present case, interstitial pneumonitis occurred approximately 2 weeks after 3 courses of chemotherapy with cyclophosphamide and doxorubicin following breast cancer surgery, and while we cannot rule out the possibility of infection, we think we were able to diagnose this as a case of drug-induced lung injury from cyclophosphamide due to the fact that there were no findings suggestive of infection in any of the tests, there was a positive challenge test for cyclophosphamide and we could not find any reports of drug-induced lung injury caused by doxorubicin. Toyoshima M, et al. [A case of early-onset cyclophosphamide-induced pneumonitis diagnosed by rechallenge test]. Nihon Kokyuki Gakkai Zasshi 47: 1082-6, No. 12, Dec 2009 [Japanese; summarised from a translation.] 803010857 Japan
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