title: A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium.
abstract: BACKGROUND
  Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort).
  
  
  METHODS
  Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated.
  
  
  RESULTS
  45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m(-2) eribulin and 1000 mg m(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts - 2/21 (CP), 1/10 (G) and 2/14 (CN).
  
  
  CONCLUSIONS
  The combination of eribulin and gemcitabine was well tolerated at the RP2D.
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G2M9.
authors.forename: S
authors.initials: S
authors.lastname: Lheureux
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G2M9.
authors.forename: A M
authors.initials: AM
authors.lastname: Oza
authors.affiliation: Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada K1H8M5.
authors.forename: S A
authors.initials: SA
authors.lastname: Laurie
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G2M9.
authors.forename: R
authors.initials: R
authors.lastname: Halford
authors.affiliation: Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada K1H8M5.
authors.forename: D
authors.initials: D
authors.lastname: Jonker
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G2M9.
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada K1H8M5.
authors.forename: D
authors.initials: D
authors.lastname: Keller
authors.affiliation: Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada K1H8M5.
authors.forename: V
authors.initials: V
authors.lastname: Bourade
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G2M9.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: CTEP, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: L
authors.initials: L
authors.lastname: Doyle
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada M5G2M9.
authors.forename: L L
authors.initials: LL
authors.lastname: Siu
authors.affiliation: Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada K1H8M5.
authors.forename: R
authors.initials: R
authors.lastname: Goel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy; D005260:Female; D005663:Furans / Q000008:administration & dosage; D006801:Humans; D007659:Ketones / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D009864:Ontario; D010051:Ovarian Neoplasms / Q000188:drug therapy; D066066:Response Evaluation Criteria in Solid Tumors; D016896:Treatment Outcome; D000093542:Gemcitabine; D000095662:Polyether Polyketides
chemical_list: D003841:Deoxycytidine; D005663:Furans; D007659:Ketones; D000093542:Gemcitabine; C490954:eribulin; D000095662:Polyether Polyketides