Sinibaldi Victoria J, Elza-Brown Kathy, Schmidt Jill, Eisenberger Mario A, Rosenbaum Eli, Denmeade Samuel R, Pili Roberto, Walczak Janet, Baker Sharyn D, Zahurak Marianna, Carducci Michael A
Prostate Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Am J Clin Oncol. 2006 Aug;29(4):395-8. doi: 10.1097/01.coc.0000225411.95479.b4.
In this phase II study, the combination of docetaxel and exisulind (a GMP phosphodiesterase inhibitor) was given to patients with metastatic androgen independent prostate cancer (AIPC) to establish efficacy, assess toxicity, and determine pharmacokinetics of docetaxel administered alone and in combination with exisulind.
Fourteen patients with metastatic AIPC were registered to receive weekly docetaxel for 4 weeks, followed by 2 weeks of rest; repeated up to a maximum of 6 cycles. Exisulind 250 mg was given orally twice a day starting on day 8 of the study and taken continuously.
All patients were evaluable for toxicity, response and survival. Grade 3 reversible toxicities included: fatigue, nausea, diarrhea, abdominal pain, rash, syncope, pulmonary edema, deep vein thrombosis, congestive heart failure, and elevations in transaminases, requiring therapy delays and/or dose reductions, or removal from therapy. Only 3 out of 14 patients (21.4%) had a 50% decline in prostate specific antigen (PSA) level that lasted > or =4 weeks; 1 out of 14 patients (7%) had a lymph node response. Median survival was 17.28 months. Docetaxel pharmacokinetics for 11 patients demonstrated mean +/- SD clearance values that were similar during week 1 and week 3 when exisulind had been added.
: Overall, our trial indicated that the toxicity profile and efficacy of this regimen is unlikely to be substantially better than single agent docetaxel.
在这项II期研究中，多西他赛与依西美坦（一种GMP磷酸二酯酶抑制剂）联合应用于转移性雄激素非依赖性前列腺癌（AIPC）患者，以确定疗效、评估毒性，并测定单独使用及与依西美坦联合使用时多西他赛的药代动力学。
14例转移性AIPC患者登记入组，接受每周一次多西他赛治疗，共4周，随后休息2周；最多重复6个周期。从研究第8天开始，口服依西美坦250 mg，每日两次，并持续服用。
所有患者均可评估毒性、反应和生存情况。3级可逆性毒性包括：疲劳、恶心、腹泻、腹痛、皮疹、晕厥、肺水肿、深静脉血栓形成、充血性心力衰竭以及转氨酶升高，需要延迟治疗和/或降低剂量，或停止治疗。14例患者中只有3例（21.4%）前列腺特异性抗原（PSA）水平下降50%且持续≥4周；14例患者中有1例（7%）有淋巴结反应。中位生存期为17.28个月。11例患者的多西他赛药代动力学显示，在加用依西美坦的第1周和第3周，平均±标准差清除率值相似。
总体而言，我们的试验表明，该方案的毒性特征和疗效不太可能比单药多西他赛有显著改善。
