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

Purpose: This multicenter phase II trial investigated the efficacy and toxi city of a combination of the novel intracellular histamine antagonist, N,N- diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), and doxorubicin i n patients with anthracycline-naive metastatic breast cancer. Preclinical m odels and early single institutional studies suggested DPPE could potentiat e the cytotoxicity of doxorubicin. Patients and Methods: Forty-two women, 32 to 77 years old (median, 59 years ), with anthracycline-naive 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) wa s administered as an 80 minute intravenous infusion with doxorubicin (60 mg /m(2)) given intravenously over the last 20 minutes of the DPPE infusion. P atients were premedicated with an antiemetic and sedating regimen. The DPPE /doxorubicin treatment was given every 21 days for a maximum of seven cycle s. 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. Thirt y-five patients received four or more cycles of chemotherapy. The overall r esponse rate was 52.5% (95% confidence interval, 36% to 68%), with 9.5% com plete responses (n = 4), 43% partial responses (n = 18), and 38% of patient s with stable disease (n = 16). Conclusion: The antitumour effects of DPPE/doxorubicin the 52.5% response r ate seems encouraging, particularly in consideration of the fact that a rec ently reported randomized National Cancer Institute of Canada Clinical Tria ls Group trial using single-agent doxorubicin 60 mg/m(2) in one of the trea tment arms achieved a 31% response rate. Thus, a randomized phase III trial of doxorubicin versus doxorubicin plus DPPE is being conducted in this cli nical setting. (C) 1999 by American Society of Clinical Oncology.