Antineoplastics Hepatitis: case report

A 36-year-old woman with breast cancer and aXillary lymph node and spinal metastases , received doxorubicin 40mg + a fluorouracil analog ('Ftorofur ') 800mg on day 1 and 8 and cyclophosphamide 150 mgj day for 11 days ('FAC' regimen) The patient experienced nausea , weakness and a slightly raised temperature followed by stomatitis and a further increase In temperature . The leucocyte count fell from 7.1 to 2.0 g j L. The patient responded to steroids + antibiotics + antlmycotlcs. Two months after the start of course 1 the patient received a second course of doxorubicin 40mg + fluorouracil analog 400mg on day 1 and cyclophosphamide 50 mgjday for 8 days. Drugs due on day 8 were missed because of a continuous fall In white blood cell count On day 16 the patient was pyretic , nauseous , was vomiting , had right upper abdominal pain and was Jaundiced . The patient responded well to prednisolone

Two months after the start of course 2, the patient was re­hospitalised because of vertebral metastatic pain. Treatment Included doxorubicin and fluorouracil analog on days 1 and 8. By days 10 and 11 , stomatitis combined with previous symptoms and a continually decreasing white blood cell count suggested drug-induced hepatitis . Readmission in a further 2 months for hypercalcaemic symptoms necessitated diuretic, prednisolone and oral phosphate solution to maintain serum calcium levels. Chemotherapy was altered to etoposide 100mg for 4 days , but was followed by stomatitis , thrush, leucooenia and a deterioration of liver function , and the patient was subicteric . The patient died 3 months later. Ulcerous stomatitis, oesophageal candidiasIs, drug-induced hepatitis and malignant metastases Involving several vertebrae were confirmed by necropsy. The liver had no metastase s present Microscopic examination showed a distorted liver architecture with the parenchymal cells and bile capillaries displaying signs of cholestasls Baseline AST and AL T levels were 19 and 33 Uj L, respectively After Increasing dUring the first course of therapy, levels dropped to 43 and 120 Uj L. respectively , before the second course Levels peaked at 640 and 4000 Uj L, respectively , then fell to 360 and 440 Uj L, respectively Other laboratory measurements of liver function showed similar changes . HBsAg was consistently negative .

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'Hepatitis developed after combined Ftorofur [fluorouracil analog] + Adriamycin [doxorubicin] + cyclophosphamide ('FAC ') medication and also after subsequent Vepesid [etoposide] monochemotherapy. · It was believed that hepatitis of this type has not been reported with cytostatic agents.

The patient's death was precipitated by the drug-related process Pa takfa ivi A Gelencser E SipOS J Acta Medica Hungarrca 44 377 385 No 4 1987

REACTIONS 2 April 1988 5