title: A phase I trial of weekly paclitaxel, 13- cis-retinoic acid, and interferon alpha in patients with prostate cancer and other advanced malignancies.
abstract: OBJECTIVE
  Based on prior studies demonstrating the effect of 13- cis-retinoic acid and interferon alpha (CRA/IFN) in decreasing the expression of the antiapoptotic protein bcl-2, our prior clinical study of CRA/IFN with paclitaxel (TAX) administered every 3 weeks, and data demonstrating increased activity of weekly TAX against prostate cancer, we designed a phase I study of weekly TAX in combination with CRA/IFN in patients with prostate cancer and other advanced malignancies. To develop a marker of drug effect, we assessed bcl-2 downregulation in patient peripheral blood mononuclear cells (PBMC).
  
  
  METHODS
  Enrolled in the study were 14 patients with prostate cancer or other advanced malignancies, and 13 were treated with 1 mg/kg CRA on days 1 and 2, 6 MU/m(2) IFN subcutaneously on days 1 and 2, and TAX at increasing doses on day 2 each week for 6 weeks out of an 8-week cycle. The effect of CRA/IFN on bcl-2 expression was assessed in PBMCs by immunoblotting.
  
  
  RESULTS
  The combination of CRA/IFN and TAX was well tolerated. Dose-limiting toxicities (DLT) in the first cycle of therapy included one patient with fever and neutropenia, and one patient with grade 4 hypertriglyceridemia. The recommended phase II dose of TAX in this combination was 80 mg/m(2). Of 13 patients assessable by tumor markers or scans, 5 had stable disease and 2 had a biochemical partial response including a patient with a decrease in PSA of >50% while on study. The assessment of patient PBMC bcl-2 was feasible in ten patients.
  
  
  CONCLUSIONS
  This is the first study in which the safety and clinical activity of weekly TAX combined with CRA/IFN has been demonstrated. The assessment of PBMC bcl-2 is feasible in this weekly chemotherapy schedule
authors.affiliation: The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA.
authors.forename: A
authors.initials: A
authors.lastname: Thalasila
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Poplin
authors.forename: J
authors.initials: J
authors.lastname: Shih
authors.forename: Dmitri
authors.initials: D
authors.lastname: Dvorzhinski
authors.forename: T
authors.initials: T
authors.lastname: Capanna
authors.forename: S
authors.initials: S
authors.lastname: Doyle-Lindrud
authors.forename: S
authors.initials: S
authors.lastname: Beers
authors.forename: S
authors.initials: S
authors.lastname: Goodin
authors.forename: Eric
authors.initials: E
authors.lastname: Rubin
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D015474:Isotretinoin / Q000008:administration & dosage; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D015474:Isotretinoin; D017239:Paclitaxel