title: Phase II trial of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl and doxorubicin chemotherapy in metastatic breast cancer: A National Cancer Institute of Canada clinical trials group study.
abstract: OBJECTIVE
  This multicenter phase II trial investigated the efficacy and toxicity of a combination of the novel intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), and doxorubicin in patients with anthracycline-naïve metastatic breast cancer. Preclinical models and early single institutional studies suggested DPPE could potentiate the cytotoxicity of doxorubicin.
  
  
  METHODS
  Forty-two women, 32 to 77 years old (median, 59 years), with anthracycline-naïve metastatic breast cancer were treated. Patients may have had one previous regimen of nonanthracycline chemotherapy, either in the adjuvant or metastatic disease treatment setting. DPPE (6 mg/kg) was administered as an 80 minute intravenous infusion with doxorubicin (60 mg/m(2)) given intravenously over the last 20 minutes of the DPPE infusion. Patients were premedicated with an antiemetic and sedating regimen. The DPPE/doxorubicin treatment was given every 21 days for a maximum of seven cycles.
  
  
  RESULTS
  All 42 patients were assessable. Overall, toxicity was comparable to that expected with doxorubicin alone, with the exception of DPPE-related motion sickness, mild hallucinations, and cerebellar signs at the time of the infusion. These CNS side effects were manageable in an ambulatory care setting, improved with subsequent cycles of treatment, and did not usually require hospitalization. Four patients developed febrile neutropenia. Thirty-five patients received four or more cycles of chemotherapy. The overall response rate was 52.5% (95% confidence interval, 36% to 68%), with 9.5% complete responses (n = 4), 43% partial responses (n = 18), and 38% of patients with stable disease (n = 16).
  
  
  CONCLUSIONS
  The antitumour effects of DPPE/doxorubicin the 52.5% response rate seems encouraging, particularly in consideration of the fact that a recently reported randomized National Cancer Institute of Canada Clinical Trials Group trial using single-agent doxorubicin 60 mg/m(2) in one of the treatment arms achieved a 31% response rate. Thus, a randomized phase III trial of doxorubicin versus doxorubicin plus DPPE is being conducted in this clinical setting.
authors.affiliation: National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), Queen's University, Kingston, ON. kkhoo@bccancer.bc.ca
authors.forename: K
authors.initials: K
authors.lastname: Khoo
authors.forename: L
authors.initials: L
authors.lastname: Brandes
authors.forename: L
authors.initials: L
authors.lastname: Reyno
authors.forename: A
authors.initials: A
authors.lastname: Arnold
authors.forename: S
authors.initials: S
authors.lastname: Dent
authors.forename: T
authors.initials: T
authors.lastname: Vandenberg
authors.forename: D
authors.initials: D
authors.lastname: Lebwohl
authors.forename: B
authors.initials: B
authors.lastname: Fisher
authors.forename: E
authors.initials: E
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D002170:Canada; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006633:Histamine Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D010647:Phenyl Ethers; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001559:Benzhydryl Compounds; D006633:Histamine Antagonists; D010647:Phenyl Ethers; D004317:Doxorubicin; C043062:tesmilifene