title: A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway.
  
  
  METHODS
  This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca alkaloid microtubule inhibitor, with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with refractory solid tumors.
  
  
  RESULTS
  Seventeen patients were treated, 10 with continuous erlotinib, and 7 with intermittent erlotinib. At dose level 1, vinflunine 280 mg/m(2) IV day 1 and erlotinib 75 mg PO days 2-21 ("continuous erlotinib") in 21 day cycles, two of four patients experienced DLTs. At dose level -1 (vinflunine 250 mg/m(2) every 21 days and erlotinib 75 mg/day), two of six patients experienced DLTs. The study was amended to enroll to "intermittent erlotinib" dosing: vinflunine day 1 and erlotinib days 2-15 of a 21 day cycle. Two of seven experienced DLTs and the study was terminated. One patient with breast cancer had a partial response; three had stable disease ≥ 6 cycles. All were treated in the continuous erlotinib group.
  
  
  CONCLUSIONS
  Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, School of Medicine, University of North Carolina at Chapel Hill, 170 Manning Drive, 3rd Floor POB, CB 7305, Chapel Hill, NC 27599-7305, USA.
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Sanoff
authors.forename: Janine M
authors.initials: JM
authors.lastname: Davies
authors.forename: Christine
authors.initials: C
authors.lastname: Walko
authors.forename: William
authors.initials: W
authors.lastname: Irvin
authors.forename: Larry
authors.initials: L
authors.lastname: Buie
authors.forename: Kimberly
authors.initials: K
authors.lastname: Keller
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.forename: Wing-Keung
authors.initials: WK
authors.lastname: Chiu
authors.forename: Bert H
authors.initials: BH
authors.lastname: O'Neil
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010641:Phenotype; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C111217:vinflunine; D014747:Vinblastine; D000069347:Erlotinib Hydrochloride; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
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