title: Interstitial pneumonia induced by combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma.
abstract: Previously we reported combined chemo-immunotherapy, using interferon (IFN)-alpha and 5-fluorouracil (5-FU) for patients with advanced hepatocellular carcinoma (HCC), and this regimen improved the prognosis. Recently, we experienced an HCC patient who died of severe interstitial pneumonia during the combined IFN-alpha and 5-FU therapy. This is the first report of the occurrence of interstitial pneumonia during combined IFN-alpha and 5-FU treatment. A 60-year-old-man was admitted to Osaka University Hospital to receive systemic chemo-immunotherapy for recurrent HCC. In the second week of the chemo-immunotherapy, he showed a decreased level of consciousness, and respiratory insufficiency. Emergency roentgenogram revealed diffuse infiltration in both lungs. Respiratory dysfunction due to interstitial pneumonia was suspected, and steroid pulse therapy was started. However, the patient showed respiratory failure, and he died 32 days after the start of the therapy. Autopsy findings showed atelectasis in the bilateral lungs, which showed elastic hard solidity and a dark red color; esophageal varices were also shown, and there was cirrhosis with a large tumor in the liver. Microscopically, the alveolar wall showed marked fibrous thickness and moderate inflammatory change, which is consistent with acute interstitial pneumonia, and the acute pulmonary change was suspected to have been the cause of death. The association of IFN with the development of interstitial pneumonia has been reported. However, the prognosis of IFN-induced interstitial pneumonia has mostly been favorable when the medication was discontinued. It has been postulated that interstitial pneumonia induced by the combination of IFN and 5-FU may be therapy-resistant. The combination of IFN-alpha and 5-FU is a useful therapy for patients with advanced HCC, such as that with portal vein invasion or multiple metastatic foci. Thus, interstitial pneumonia in these patients should be carefully managed.
authors.affiliation: Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871 Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Norishige
authors.initials: N
authors.lastname: Iizuka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.forename: Masato
authors.initials: M
authors.lastname: Sakon
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D017809:Fatal Outcome; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000009:adverse effects / Q000633:toxicity*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008168:Lung / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D011169:Portal Vein / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D016898:Interferon-alpha; D005472:Fluorouracil