Brandes L J, Bracken S P, Ramsey E W
Department of Medicine, Manitoba Cancer Treatment and Research Foundation, Winnipeg, Canada.
J Clin Oncol. 1995 Jun;13(6):1398-403. doi: 10.1200/JCO.1995.13.6.1398.
The intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine. HCl (DPPE), potentiates chemotherapy cytotoxicity to malignant cells but protects normal tissue, including bone marrow, gut, and hair. We assessed the response to and clinical toxicity of DPPE/cyclophosphamide therapy in 20 patients with advanced hormonally unresponsive prostate cancer, 19 of whom were symptomatic.
Subjects received a maximally tolerated dose of DPPE (6 mg/kg) intravenously (IV) over 80 minutes. Cyclophosphamide (600 to 800 mg/m2; maximum dose, 1,500 mg) was administered over the last 20 minutes of DPPE infusion. Treatments (usually outpatient) were given once weekly for 4 weeks, followed by a 1-week delay, and then 2 of every 3 weeks as long as the patient was deemed to benefit.
Five of seven patients (71%) with measurable soft tissue disease had a partial 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 more 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, respectively. 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 tiredness and mild nausea; one patient developed hemorrhagic cystitis. Bone marrow and hair follicle toxicity was negligible in 14 and 15 patients, respectively.
DPPE/cyclophosphamide appears to be an active regimen for metastatic prostate cancer, with the added benefit of relatively low toxicity.
细胞内组胺拮抗剂N，N - 二乙基 - 2 - [4 -（苯甲基）苯氧基]乙胺·盐酸盐（DPPE）可增强化疗对恶性细胞的细胞毒性，但能保护包括骨髓、肠道和毛发在内的正常组织。我们评估了20例晚期激素难治性前列腺癌患者接受DPPE/环磷酰胺治疗的反应及临床毒性，其中19例有症状。
受试者在80分钟内静脉注射最大耐受剂量的DPPE（6mg/kg）。在DPPE输注的最后20分钟给予环磷酰胺（600至800mg/m²；最大剂量1500mg）。治疗（通常为门诊治疗）每周进行1次，共4周，随后休息1周，然后只要患者被认为有益，每3周进行2次。
7例有可测量软组织疾病的患者中有5例（71%）部分缓解（PR）。16例可评估骨疾病患者中有3例（19%）有反应（1例完全缓解[CR]和2例PR）。18例前列腺特异性抗原（PSA）血清水平升高的患者中有9例（50%）下降超过50%（平均±标准差，78%±14%）。13例有骨痛的患者中有11例（85%）该症状部分或完全缓解；这些患者中有6例PSA水平改善，2例骨扫描改善。急性治疗毒性包括恶心/呕吐（20例中的6例）和共济失调（20例中的20例），这与DPPE的血清峰值水平相关。延迟效应（24至48小时）主要包括疲劳和轻度恶心；1例患者发生出血性膀胱炎。14例患者的骨髓毒性和15例患者的毛囊毒性可忽略不计。
DPPE/环磷酰胺似乎是转移性前列腺癌的一种有效治疗方案，且具有毒性相对较低的额外益处。
