title: A phase 1/1b study of satraplatin (JM-216) in combination with docetaxel in patients with advanced solid tumors and metastatic castrate-resistant prostate cancer.
abstract: BACKGROUND
  Satraplatin is an oral platinum with potential advantages over other platinum agents. This study investigated the combination of satraplatin and docetaxel in a phase 1 study of patients with advanced solid tumor malignancies followed by a phase 1b study in men with chemotherapy naïve metastatic castrate-resistant prostate cancer (CRPC).
  
  
  METHODS
  In this single institution phase 1/1b study, patients received docetaxel on day 1 and satraplatin on days 1-5 of a 21-day cycle ± granulocyte colony stimulating factor (GCSF). For phase 1b, prednisone 10 mg daily was added.
  
  
  RESULTS
  Twenty-nine patients received treatment. Based on 3 dose limiting toxicities (DLT) (grade 4 neutropenia) in 13 patients at dose levels 1 and -1 (docetaxel 60 mg/m(2) plus satraplatin 40 mg/m(2) and docetaxel 60 mg/m(2) plus satraplatin 50 mg/m(2)) GCSF was administered with subsequent cohorts. A dose level of docetaxel 60 mg/m(2) plus satraplatin 50 mg/m(2) with GCSF was the starting dose level for phase 1b. At the highest dose in the phase 1b (docetaxel 75 mg/m(2) plus satraplatin 50 mg/m(2)) there were no DLTs.
  
  
  CONCLUSIONS
  The combination of satraplatin and docetaxel is feasible in solid tumor malignancies. In advanced malignancies, the recommended phase 2 dose is docetaxel 60 mg/m(2) IV day 1 with satraplatin 40 mg/m(2)/d PO days 1-5, without G-CSF, and Docetaxel 70 mg/m(2) IV day 1 with Satraplatin 50 mg/m(2)/day PO days 1-5, with G-CSF support, repeated in 3-week cycles. For patients with CRPC the recommended phase 2 dose is docetaxel 75 mg/m(2) IV day 1 with satraplatin 50 mg/m(2)/d PO days 1--5, with G-CSF and prednisone 10 mg daily, repeated in 3-week cycles.
authors.affiliation: University of Wisconsin Carbone Cancer Center, Wisconsin Institutes for Medical Research, Madison, WI 53705, USA. jpcetnar@medicine.wisc.edu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Cetnar
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Douglas
authors.initials: D
authors.lastname: McNeel
authors.forename: Noelle K
authors.initials: NK
authors.lastname: LoConte
authors.forename: Thomas A
authors.initials: TA
authors.lastname: McFarland
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002369:Castration; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C081294:satraplatin