Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Cancer. 2013 Sep 1;119(17):3186-94. doi: 10.1002/cncr.28103. Epub 2013 Jun 13.
β-emitting bone-seeking radiopharmaceuticals have historically been administered for pain palliation whereas docetaxel prolongs life in patients with metastatic castration-resistant prostate cancer (mCRPC). In combination, these agents simultaneously target the bone stroma and cancer cell to optimize antitumor effects. The toxicity and efficacy when each agent is combined at full, recommended doses, in a repetitive fashion is not well established.
Patients with progressive mCRPC and ≥ 3 bone lesions received (153) Sm-EDTMP (samarium-153 ethylene diamine tetramethylene phosphonate) at a dose of 1.0 mCi/kg every 9 weeks and docetaxel at a dose of 75 mg/m(2) every 3 weeks. In the absence of unacceptable toxicity, patients were allowed to continue additional cycles, defined by 9 weeks of treatment, until intolerance or biochemical/radiographic disease progression.
Of the 30 patients treated, approximately 50% were considered to be taxane-naive, 36.7% were taxane-refractory, and 13.3% had previously been exposed to taxanes but were not considered refractory. Patients received on average 2.5 cycles of treatment (6.5 doses of docetaxel and 2.5 doses of (153) Sm-EDTMP). Twelve patients (40%) demonstrated a decline in their prostate-specific antigen level of ≥ 50%. The median progression-free survival (biochemical or radiographic) was 7.0 months and the overall survival was 14.3 months. Nine patients (30%) did not recover platelet counts >100 K/mm(3) after a median of 3 cycles to allow for additional treatment, with 4 patients experiencing prolonged thrombocytopenia. The most common reasons for trial discontinuation were progressive disease and hematologic toxicity.
The results of the current study indicate that (153) Sm-EDTMP can be safely combined with docetaxel at full doses on an ongoing basis in patients with mCRPC. Although thrombocytopenia limited therapy for some patients, preliminary efficacy supports the strategy of combining a radiopharmaceutical with chemotherapy, which is an appealing strategy given the anticipated availability of α emitters that can prolong survival.
β发射骨靶向放射性药物在历史上一直被用于缓解疼痛，而多西他赛可延长转移性去势抵抗性前列腺癌（mCRPC）患者的生命。联合使用时，这些药物同时靶向骨基质和癌细胞，以优化抗肿瘤效果。当以全剂量、重复方式联合使用每种药物时，其毒性和疗效尚未得到充分证实。
进展期 mCRPC 且≥3 处骨转移患者接受（153）Sm-EDTMP（锝-153 乙二胺四甲撑膦酸），剂量为 1.0mCi/kg，每 9 周一次；多西他赛，剂量为 75mg/m2，每 3 周一次。在无不可接受毒性的情况下，允许患者继续接受额外的周期治疗，即 9 周的治疗，直至无法耐受或出现生化/影像学疾病进展。
30 例患者中，约 50%被认为是紫杉烷初治患者，36.7%是紫杉烷耐药患者，13.3%之前接受过紫杉烷治疗，但不认为是耐药患者。患者平均接受了 2.5 个周期的治疗（6.5 剂多西他赛和 2.5 剂（153）Sm-EDTMP）。12 例患者（40%）的前列腺特异性抗原水平下降≥50%。中位无进展生存期（生化或影像学）为 7.0 个月，总生存期为 14.3 个月。9 例患者（30%）在中位数为 3 个周期后，血小板计数仍未恢复至>100 K/mm3，无法进行额外的治疗，其中 4 例患者出现持续性血小板减少。试验终止的最常见原因是疾病进展和血液学毒性。
本研究结果表明，（153）Sm-EDTMP 可在 mCRPC 患者中以全剂量持续安全地与多西他赛联合使用。虽然血小板减少限制了一些患者的治疗，但初步疗效支持联合使用放射性药物和化疗的策略，考虑到预期可用的α发射体可延长生存期，这是一种很有吸引力的策略。
