Gemcitabine-Induced Pulmonary Toxicity: A Case Report of Pulmonary Veno-Occlusive Disease

Abstract

INTRODUCTIONGemcitabine is a chemotherapeutic agent frequently used by for the treatment of several malignancies both in the adjuvant and metastatic setting. Although myelosuppression is the most adverse event of this therapy, gemcitabine might induce severe pulmonary toxicities. We describe a case of pulmonary veno-occlusive disease (PVOD) related to gemcitabine.CASE PRESENTATIONThe patient was an 83-year-old man with a metastatic pancreatic cancer who was treated by gemcitabine as first-line therapy. He was in good health and received no other chemotherapy. A dose of 1000 mg/m2 of gemcitabine was administered over a 30-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. After a period of 6 months, a complete response was observed. Nevertheless, the patient developed a severe dyspnea, with arterial hypoxemia and very low lung diffusion for carbon monoxide. A CT scan showed diffuse ground glass opacities with septal lines, bilateral pleural effusion, and lymph node enlargement. On echocardiography, there was a suspicion of pulmonary hypertension with elevated systolic pulmonary artery pressure and normal left ventricular pressures. Right heart catheterization confirmed pulmonary hypertension and normal pulmonary artery occlusion pressure. Diagnosis of PVOD was made, and a gemcitabine-induced toxicity was suspected. A symptomatic treatment was started. At last follow-up, patient was in functional class I with near-normal of CT scan, arterial blood gases, and echocardiography. A gemcitabine-induced PVOD is the more likely diagnosis.

Tumoral pulmonary hypertension

“…Clinical features include marked oxygen desaturation and very low gas transfer, with a radiographic triad of interlobular septal thickening, pleural effusions and lymphadenopathy. PVOD has been described in patients receiving chemotherapy including gemcitabine [83] and mitomycin-C [79,[84][85][86], and also in several reports following bone marrow transplantation [80,[86][87][88]. Radiotherapy has been reported to induce PVOD, with a potential delay in onset for several years, for example following mantle irradiation for Hodgkin's lymphoma.…”

Pulmonary tumour thrombotic microangiopathy

“…Chemotherapeutic agents including gemcitabine [45] and mitomycin-C may cause pulmonary veno-occlusive disease [46,47], and the PDGF inhibitor dasatinib may actually cause PAH [48]. In addition, chemotherapy and radiation-induced left heart dysfunction may cause group 2 pulmonary hypertension [49].…”

A Rare Case of Gemcitabine-Induced Pulmonary Hypertension

“…Various types of lung injuries have been reported with gemcitabine use including interstitial pneumonitis, diffuse alveolar damage, pulmonary fibrosis, and acute respiratory distress syndrome. 5,6 While the exact mechanism is unknown, several hypotheses have been proposed to explain the pathogenesis of GIPT. For example, the induction of pro-inflammatory cytokines and an enhanced expression of growth factors are linked to idiopathic pulmonary fibrosis related to gemcitabine use.…”