Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer
Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer
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DOI：
10.1089/hum.2007.074
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发表时间：
2007-12-01
影响因子：
4.2
通讯作者：
Gotoh, Akinobu
中科院分区：
文献类型：
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作者：
Shirakawa, Toshiro;Terao, Shuji;Gotoh, Akinobu
我们评估了Ad-OC-TK（携带骨钙素启动子驱动的单纯疱疹病毒胸苷激酶基因的重组腺病毒载体）联合瓦尔（伐昔洛韦）基因治疗难治性前列腺癌的长期安全性和有效性。Ad-OC-TK/瓦尔疗法是第一种用于治疗转移性前列腺癌（包括骨转移）的体内腺病毒介导的基因疗法。本试验入组了6名患者，在第1天和第8天将两个剂量的Ad-OC-TK（2.5 × 10（9）或2.5 × 10（10）空斑形成单位）注射到局部复发性肿瘤或骨转移瘤中。患者还接受瓦尔（3 g/天）治疗21天。对每例患者进行至少8个月的安全性和有效性评价。所有患者均耐受该治疗，无严重不良事件。观察到1例前列腺特异性抗原（PSA）缓解（从318.3至4.9 ng/ml），至PSA进展时间（TTP）为12个月。对3例基因治疗后PSA失败的紫杉醇初治患者给予多西他赛（30 mg/m2/周）和雌莫司汀（560 mg/天）联合化疗（DE）。所有3例患者均对DE治疗有PSA应答，TTP分别为21、7和4个月。这些结果表明，需要进行更多的试验。
We evaluated the long-term safety and efficacy of Ad-OC-TK (recombinant adenoviral vector carrying an osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) gene therapy for hormone-refractory prostate cancer. Ad-OC-TK/VAL therapy is the first in vivo adenovirus-mediated gene therapy to be used to treat metastatic prostate cancer, including bone metastasis. Six patients were enrolled in this trial, and two doses of Ad-OC-TK (2.5 x 10(9) or 2.5 x 10(10) plaque-forming units) were injected into locally recurrent tumor or bone metastasis on day 1 and day 8. Patients were also given VAL (3 g/day) for 21 days. Safety and efficacy were evaluated for at least 8 months in each patient. All patients tolerated this therapy with no serious adverse events. One prostate-specific antigen (PSA) response (from 318.3 to 4.9 ng/ml) was observed with a time to PSA progression (TTP) of 12 months. Docetaxel (30 mg/m(2) per week) and estramustine (560 mg/day) combination chemotherapy (DE) was given to three docetaxel-naive patients on PSA failure after gene therapy. All three patients had a PSA response to DE therapy with 21, 7, and 4 months of TTP. These results suggest that additional trials are warranted.