Mackler Niklas J, Pienta Kenneth J, Dunn Rodney L, Cooney Kathleen A, Redman Bruce G, Olson Karin B, Fardig Judith E, Smith David C
Department of Internal Medicine, Division of Hematology/Oncology University of Michigan Medical School.
Clin Genitourin Cancer. 2007 Jun;5(5):318-22. doi: 10.3816/CGC.2007.n.010.
The primary objective of this study was to assess the feasibility and efficacy of administering etoposide/estramustine/paclitaxel in hormone-sensitive metastatic prostate cancer responding to hormonal therapy.
Eligible patients had metastatic prostate cancer and had received combined androgen blockade for 6-8 months with a > or = 80% decrease in prostate-specific antigen from pretreatment. They received 4 cycles of chemotherapy consisting of estramustine 280 mg orally 3 times daily, etoposide 50 mg/m2 orally on days 1-14, and paclitaxel 135 mg/m2 intravenously for 1 hour on day 2 of each 21-day cycle and were then followed until time to treatment failure (TTF).
Twenty-six patients were evaluable for response and toxicity. Median TTF was 21.7 months (range, 11.9-64.5 months; 95% confidence interval, 15.3-26.2 months). Median survival from time of initiation of hormone therapy was 5.1 years. Neutropenia was the most common grade 3/4 toxicity, occurring in 3 patients. Significant toxicities were limited to nausea, diarrhea, and febrile neutropenia in 3 patients, respectively.
The administration of paclitaxel/estramustine/etoposide in this setting is feasible and well tolerated. Although the TTF of 21.7 months by prostate-specific antigen criteria is similar to historical controls in the emergence of clinically evident androgen-independent disease after starting hormone therapy, direct comparisons cannot be made. More trials are needed to investigate the timing of chemotherapy in patients with prostate cancer.
本研究的主要目的是评估在对激素治疗有反应的激素敏感性转移性前列腺癌中给予依托泊苷/雌莫司汀/紫杉醇的可行性和疗效。
符合条件的患者患有转移性前列腺癌，已接受联合雄激素阻断治疗6 - 8个月，前列腺特异性抗原较治疗前降低≥80%。他们接受4个周期的化疗，包括每天口服3次280 mg雌莫司汀，在每个21天周期的第1 - 14天口服50 mg/m²依托泊苷，在每个周期的第2天静脉输注135 mg/m²紫杉醇1小时，然后随访至治疗失败时间（TTF）。
26例患者可评估反应和毒性。中位TTF为21.7个月（范围11.9 - 64.5个月；95%置信区间15.3 - 26.2个月）。从激素治疗开始的中位生存期为5.1年。中性粒细胞减少是最常见的3/4级毒性，3例患者出现。严重毒性分别仅限于3例患者的恶心、腹泻和发热性中性粒细胞减少。
在这种情况下给予紫杉醇/雌莫司汀/依托泊苷是可行的且耐受性良好。尽管根据前列腺特异性抗原标准21.7个月的TTF与激素治疗开始后临床明显出现雄激素非依赖性疾病的历史对照相似，但无法进行直接比较。需要更多试验来研究前列腺癌患者化疗的时机。
