title: Tesetaxel, a new oral taxane, in combination with capecitabine: a phase I, dose-escalation study in patients with advanced solid tumors.
abstract: OBJECTIVE
  This phase I study was conducted primarily to determine the maximum tolerated dose (MTD) of tesetaxel, a novel, orally active, semisynthetic microtubule inhibitor of the taxane class, administered with oral capecitabine to patients with advanced solid tumors.
  
  
  METHODS
  During each 21-day cycle, patients were to receive tesetaxel on Day 1 and capecitabine twice daily on Days 1 through 14. The starting dose was tesetaxel 18 mg/m(2) and capecitabine 1,250 mg/m(2)/day. These doses were increased based on tolerability during the first cycle according to the protocol-specified dose-escalation scheme. Response was evaluated every other treatment cycle according to RECIST. Serial blood samples were collected during the first and second cycles to explore possible pharmacokinetic drug interactions.
  
  
  RESULTS
  Twenty-seven patients were enrolled and treated. The most frequently reported dose-limiting toxicities were neutropenia and febrile neutropenia, with individual patients experiencing dose-limiting stomatitis and diarrhea. The MTD for the treatment regimen was defined as tesetaxel 27 mg/m(2) and capecitabine 2,500 mg/m(2)/day. The most common ≥ Grade 3 treatment-related adverse events included leukopenia (44% of patients) and neutropenia (41%). Of 22 evaluable patients, the best overall response was stable disease in 82% and progressive disease in 18%. No meaningful pharmacokinetic drug interactions were apparent.
  
  
  CONCLUSIONS
  The results of this study demonstrate that these two orally active agents can be combined at the individual MTD of each drug with acceptable toxicity. These data further support the continued clinical development of tesetaxel both as a single agent and in combination with other active cancer therapeutics.
authors.affiliation: University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, AL, USA. mws2138@columbia.edu
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
authors.forename: John
authors.initials: J
authors.lastname: Sarantopoulos
authors.forename: Amita
authors.initials: A
authors.lastname: Patnaik
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Tolcher
authors.forename: Chris
authors.initials: C
authors.lastname: Takimoto
authors.forename: Murali
authors.initials: M
authors.lastname: Beeram
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; C479543:tesetaxel