title: Pazopanib and pancreatic toxicity: a case report.
abstract: BACKGROUND
  Pazopanib is an oral multitargeted tyrosine-kinase inhibitor, used as a single agent to treat advanced renal cell carcinoma. Treatment with other tyrosine-kinase inhibitors is known to be associated with asymptomatic elevations of serum amylase and lipase levels. As regards the pazopanib, data are lacking in literature.
  
  
  METHODS
  We report one case of pancreatic toxicity associated with pazopanib administration. Before starting treatment, patient had no risk factors for pancreatitis. The patient, an Italian 68 years old woman, started pazopanib at doses of 800 mg daily as first-line therapy for metastatic renal cell carcinoma. Six months after the start of treatment, blood tests showed for the first time a significant increase in serum lipase and amylase in the absence of symptoms and radiological findings of pancreatitis. The patient continued treatment without interruptions or dose reductions. However, the continuation of the treatment led to a further increase of pancreatic enzymes. We tried to continue the treatment by reducing the dose but only the discontinuation was associated with normalization of amylase and lipase's levels. On the other hand the treatment with pazopanib got prolonged response of the disease in the absence of signs of pancreatitis. We therefore decided to continue treatment with pazopanib 400 mg daily with close monitoring of blood levels of pancreatic enzymes.
  
  
  CONCLUSIONS
  We hypothesize that the increase of pancreatic enzymes is not a dose-dependent event. The mechanism for pancreatic toxicity induced by tyrosine-kinase inhibitors is unknown and no predictive factors have been identified. There are no clear guidelines on the management of the drug in the presence of pancreatic enzyme increase. In any case, we believe that a careful monitoring of pancreatic enzymes during treatment with pazopanib is advisable.
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. m.russano@unicampus.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Russano
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. b.vincenzi@unicampus.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. o.venditti@unicampus.it.
authors.forename: Olga
authors.initials: O
authors.lastname: Venditti
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. l.donofrio@unicampus.it.
authors.forename: Loretta
authors.initials: L
authors.lastname: D'Onofrio
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. r.ratta@unicampus.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ratta
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. f.guida@unicampus.it.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Guida
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. g.tonini@unicampus.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. d.santini@unicampus.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
mesh_terms: D000368:Aged; D000681:Amylases / Q000097:blood; D005260:Female; D006801:Humans; D007191:Indazoles; D008049:Lipase / Q000097:blood; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D008049:Lipase; D000681:Amylases