title: Gemcitabine-induced severe pulmonary toxicity.
abstract: Gemcitabine is a relatively new deoxycytidine analog (2',2'-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine-induced severe pulmonary toxicity (GISPT) were reported as for Ara-C. We performed a systematic review of reported cases on the GISPT. Twenty-nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X-ray are reticulo-nodular interstitial infiltrates. It was postulated that the physio-pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. Its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration.
authors.affiliation: Département des Maladies Respiratoires, Faculty of Medicine, University de la Méditerranée (Aix-Marseille II), Assistance Publique-Hôpitaux de Marseille, France. fabrice.barlesi@mail.ap-hm.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlési
authors.forename: Patrick
authors.initials: P
authors.lastname: Villani
authors.forename: Christophe
authors.initials: C
authors.lastname: Doddoli
authors.forename: Céline
authors.initials: C
authors.lastname: Gimenez
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kleisbauer
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy; D003841:Deoxycytidine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003937:Diagnosis, Differential; D018450:Disease Progression; D004347:Drug Interactions; D004417:Dyspnea / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000628:therapy; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary; D013902:Radiography, Thoracic / Q000009:adverse effects; D012307:Risk Factors; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine