Hussain M, Petrylak D, Fisher E, Tangen C, Crawford D
Department of Internal Medicine, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
Semin Oncol. 1999 Oct;26(5 Suppl 17):55-60.
Hormone-refractory prostate cancer is the terminal step in the natural history of prostate cancer. To date, no chemotherapeutic agents have been shown to impact clinical outcome at this stage. Recently, the Food and Drug Administration approved the combination of mitoxantrone and prednisone based solely on its superior palliative effects as compared to steroids alone in 2 randomized trials. Progress in biologically driven drug development has led to the identification of several estramustine-based regimens that, although based on single institution experience, appear to have at least a comparable but very promising level of activity in hormone-refractory prostate cancer patients. One such combination, estramustine plus docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA), is particularly attractive because of its convenient schedule and side effect profile. To objectively assess the therapeutic benefit of this combination, the Southwest Oncology Group is initiating a randomized phase III trial comparing estramustine and docetaxel with the standard arm of mitoxantrone and prednisone using time to progression and survival as the primary end points. Secondary end points will include toxicity profiles, assessments of quality of life parameters, and magnitude of decline of prostate-specific antigen levels between the two treatment arms.
激素难治性前列腺癌是前列腺癌自然病程中的终末阶段。迄今为止，尚无化疗药物被证实能在此阶段影响临床结局。最近，美国食品药品监督管理局仅基于米托蒽醌与泼尼松联合用药在两项随机试验中相较于单独使用类固醇具有更优的姑息治疗效果，批准了该联合用药方案。生物驱动的药物研发取得进展，已确定了几种基于雌莫司汀的治疗方案，尽管这些方案是基于单一机构的经验，但在激素难治性前列腺癌患者中似乎至少具有相当且前景十分可观的活性水平。其中一种联合用药方案，即雌莫司汀加多西他赛（泰索帝；罗纳普朗克·罗雷尔公司，宾夕法尼亚州考利奇维尔），因其给药方案便捷且副作用情况良好而格外具有吸引力。为客观评估该联合用药方案的治疗益处，西南肿瘤协作组正在开展一项随机III期试验，以疾病进展时间和生存期作为主要终点，将雌莫司汀与多西他赛联合用药方案与米托蒽醌和泼尼松的标准治疗方案进行比较。次要终点将包括毒性情况、生活质量参数评估以及两个治疗组之间前列腺特异性抗原水平下降的幅度。
