Age-stratified phase I trial of a combination of bortezomib, gemcitabine, and liposomal doxorubicin in patients with advanced malignancies
Age-stratified phase I trial of a combination of bortezomib, gemcitabine, and liposomal doxorubicin in patients with advanced malignancies
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DOI：
10.1007/s00280-011-1808-4
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发表时间：
2012-05-01
影响因子：
3
通讯作者：
Kurzrock, R.
中科院分区：
文献类型：
--
作者：
Falchook, G. S.;Duvic, M.;Kurzrock, R.
临床前数据表明硼替佐米、吉西他滨和多柔比星脂质体的协同活性。由于老年患者对治疗的耐受性可能会减弱，我们对该组合进行了年龄分层的I期试验，两个平行的年龄分层组（< 65岁和每千日元65岁）（3 + 3设计）。起始剂量包括硼替佐米0.7 mg/m（2）（第1天和第8天），吉西他滨500 mg/m（2）在< 65岁组中，65例患者接受了阿霉素脂质体20 mg/m2（第1天）治疗;最大耐受剂量为硼替佐米1.3 mg/m2、吉西他滨800 mg/m2和脂质体阿霉素35 mg/m2。在千分之一日元65岁组中，28例患者接受治疗;推荐的II期剂量为硼替佐米1.0 mg/m2，吉西他滨800 mg/m2和脂质体阿霉素20 mg/m2。剂量限制性毒性包括血小板减少和中性粒细胞减少。最常见的毒性反应为轻度血细胞减少、疲乏和神经病变。10例患者获得部分缓解（7例皮肤T细胞淋巴瘤患者中有6例; 16例小细胞癌患者中有4例，包括肺癌、前列腺癌、卵巢癌和鼻咽癌）。硼替佐米、吉西他滨和脂质体多柔比星联合治疗耐受性良好，但老年患者的II期推荐剂量较低，并显示出抗肿瘤活性，尤其是在T细胞和小细胞组织学恶性肿瘤中。
Preclinical data suggest synergistic activity of bortezomib, gemcitabine, and liposomal doxorubicin. Because tolerance to therapy may be attenuated in elderly patients, we performed an age-stratified phase I trial of this combination.Two parallel age-stratified arms (< 65 and a parts per thousand yen65 years old) were accrued (3 + 3 design). Starting doses included bortezomib 0.7 mg/m(2) (days 1 and 8), gemcitabine 500 mg/m(2) (days 1 and 8), and liposomal doxorubicin 20 mg/m(2) (day 1).In the < 65-year-old group, 65 patients were treated; the maximum-tolerated dose was bortezomib 1.3 mg/m(2), gemcitabine 800 mg/m(2), and liposomal doxorubicin 35 mg/m(2). In the a parts per thousand yen65-year-old group, 28 patients were treated; the recommended phase II dose was bortezomib 1.0 mg/m(2), gemcitabine 800 mg/m(2), and liposomal doxorubicin 20 mg/m(2). Dose-limiting toxicities included thrombocytopenia and neutropenia. The most common toxicities were mild cytopenias, fatigue, and neuropathy. Ten patients achieved partial responses (6 of 7 patients with cutaneous T-cell lymphoma; 4 of 16 patients with small cell carcinomas, including lung, prostate, ovarian, and nasopharyngeal).Combination of bortezomib, gemcitabine, and liposomal doxorubicin is well tolerated, but with a lower recommended phase II dose in elderly patients, and demonstrated antitumor activity, especially in T-cell and small cell histology malignancies.