title: Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of masitinib combined with gemcitabine in patients with advanced pancreatic cancer.
  
  
  METHODS
  Twenty-two non-randomised patients with unresectable, locally advanced (n = 9) or metastatic pancreatic cancer (n = 13) received oral masitinib (9 mg/kg/day) combined with standard gemcitabine. All patients were naive to systemic chemotherapy or radiotherapy. The primary endpoint was time-to-progression (TTP) with efficacy and safety analyses performed on the intent-to-treat population. Secondary endpoints included overall survival (OS), as well as, subgroup analyses according to baseline disease, and performance status.
  
  
  RESULTS
  Overall median TTP was 6.4 months (95% CI [2.7-11.7]); 8.3 and 2.7 months, respectively, for locally advanced and metastatic patients; 6.4 and 0.8 months, respectively, for patients with KPS [80-100] or KPS [70]. Median OS was 7.1 months (95% CI [4.8-17.0]); 8.4 and 6.8 months for locally advanced or metastatic patients, respectively; 8.0 and 4.4 months in patients with KPS [80-100] or KPS [70], respectively. The 18-month observed survival rate was similar for locally advanced (22%) and metastatic patients (23%) and reached 28% for KPS [80-100] patients. The most common suspected adverse events were nausea, vomiting, rash, diarrhoea, peripheral oedema, anaemia, lymphopenia, thrombocytopenia, pyrexia, neutropenia, asthenia, leucopenia, and abdominal pain, and most were of grades 1-2 severity.
  
  
  CONCLUSIONS
  The efficacy and safety of masitinib combined with gemcitabine are encouraging, with extended survival and median TTP that support initiation of a phase 3 trial.
authors.affiliation: Hépato-gastroentérologie et oncologie digestive, Assistance Publique des Hôpitaux de Paris, Hôpital Ambroise Paré, 92104, Boulogne Billancourt, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mitry
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.forename: Gaël
authors.initials: G
authors.lastname: Deplanque
authors.forename: Françoise
authors.initials: F
authors.lastname: Mornex
authors.forename: Philippe
authors.initials: P
authors.lastname: Levy
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.forename: Alain
authors.initials: A
authors.lastname: Moussy
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kinet
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Philippe
authors.initials: P
authors.lastname: Rougier
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines; D011725:Pyridines; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D001549:Benzamides; D010880:Piperidines; D011725:Pyridines; D013844:Thiazoles; D003841:Deoxycytidine; C526575:masitinib; D000093542:Gemcitabine