N,N-DIETHYL-2-[4-(PHENYLMETHYL)PHENOXY]ETHANAMINE IN COMBINATION WITHCYCLOPHOSPHAMIDE - AN ACTIVE, LOW-TOXICITY REGIMEN FOR METASTATIC HORMONALLY UNRESPONSIVE PROSTATE-CANCER

Purpose: The intracellular histamine antagonist, N,N-diethyl-2-[4-(phe nylmethyl)phenoxy]ethanamine. HCl (DPPE), potentiates chemotherapy cyt otoxicity to malignant cells but protects normal tissue, including bon e marrow, gut and hair. We assessed the response to and clinical toxic ity of DPPE/cyclophosphamide therapy in 20 patients with advanced horm onally unresponsive prostate cancer, 19 of whom were symptomatic. Pati ents and Methods: Subjects received a maximally tolerated dose of DPPE (6 mg/kg) intravenously (IV) over 80 minutes. Cyclophosphamide (600 t o 800 mg/m(2); maximum dose, 1,500 mg) was administered over the last 20 minutes of DPPE infusion. Treatments (usually outpatient) were give n once weekly for 4 weeks, followed by a 1-week delay, and then 2 of e very 3 weeks as long as the patient was deemed to benefit. Results: Fi ve of seven patients (71%) with measurable soft tissue disease had a p artial remission (PR). Three of 16 (19%) with assessable bone disease responded (one complete remission [CR] and two PRs). Nine of 18 (50%) with an elevated serum level of prostate-specific antigen (PSA) had mo re than a 50% (mean +/- SD, 78% +/- 14%) decrease. Eleven of 13 (85%) with bone pain had partial or complete resolution of this symptom; the PSA level and bone scan improved in six and two of these subjects, re spectively. Acute treatment toxicity consisted of nausea/vomiting (six of 20) and ataxia (20 of 20), which correlated with peak serum levels of DPPE. Delayed effects (24 to 48 hours) consisted mainly of tiredne ss and mild nausea; one patient developed hemorrhagic cystitis. Bone m arrow and hair follicle toxicity was negligible in 14 and 15 patients, respectively. Conclusion: DPPE/cyclophosphamide appears to be an acti ve regimen for metastatic prostate cancer, with the added benefit of r elatively low toxicity. (C) 1995 by American Society of Clinical Oncol ogy.