Phase II clinical trial of titanocene dichloride in patients with metastatic breast cancer
Phase II clinical trial of titanocene dichloride in patients with metastatic breast cancer
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DOI：
10.1159/000027075
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发表时间：
2000-02-01
期刊：
影响因子：
0.3
通讯作者：
Hossfeld, DK
中科院分区：
文献类型：
--
作者：
Kroger, N;Kleeberg, UR;Hossfeld, DK
背景资料：二氯化二茂钛（MKT 4）是最近开发的细胞生长抑制剂，对裸鼠人乳腺癌异种移植模型显示出临床前活性。进行了II期试验，以评估这种无机早期过渡金属络合物在转移性乳腺癌患者中的临床活性。患者和方法：15例患者入组本多中心II期试验。12例中位年龄为58岁的患者符合毒性和缓解条件。所有12例患者在入组研究时均有既往手术和转移性疾病。7例患者既往接受过放疗，9例患者既往接受过激素治疗，8例患者既往接受过辅助化疗。既往未接受过转移性疾病化疗。静脉注射二氯化二茂钛，剂量为270 mg/m2，每3周一次。结果：在12例符合条件的可评价反应的患者中，未观察到客观缓解。2名患者（17%）表现出“轻微缓解”：5名患者（42%）的疾病“无变化”。大多数患者发生影响胃肠道、神经系统、肝脏和肾脏系统的中度至重度药物相关毒性（CTC II-III级）。因此，在5例患者中，剂量不得不降低至240 mg/m2。结论：在该方案中，以240-270 mg/m2的剂量给予MKT 4对转移性乳腺癌患者无效。当MKT 4剂量降至240 mg/m2时，3周一次给药方案的耐受性可接受（2）。
Background: Titanocene dichloride (MKT4) is a recently developed cytostatic agent that shows preclinical activity against human breast cancer xenograft models in nude mice. A phase II trial was conducted to evaluate the clinical activity of this inorganic early-transition metal complex in patients with metastatic breast cancer. Patients and Methods: Fifteen patients were enrolled into this multicenter phase II trial. Twelve patients with a median age of 58 years were eligible for toxicity and response. All 12 patients had prior surgery and metastatic disease at study entry. Seven patients had prior radiotherapy, 9 patients had prior hormone therapy, and 8 patients had prior adjuvant chemotherapy. No previous chemotherapy for metastatic disease was allowed. Titanocene dichloride was intravenously administered at a dose of 270 mg/m(2) every 3 weeks. Results: Among the 12 eligible patients evaluable for response, no objective remission was observed. Two patients (17%) showed a 'minor remission: and 5 patients (42%) experienced a 'no change' situation of their disease. Moderate to severe drug-related toxicities (CTC grade II-III) affecting the gastrointestinal, neurological, hepatic and renal system occurred in the majority of patients. Therefore, in 5 patients the dose had to be reduced to 240 mg/m(2). Conclusion: MKT4, given at a dose of 240-270 mg/m(2) in this schedule, was not effective in patients with metastatic breast cancer. The tolerability of the 3-weekly dosing regimen was acceptable when the MKT4 dose was reduced to 240 mg/m(2).