Treatment of anaplastic thyroid carcinoma with paclitaxel: Phase 2 trial using ninety-six-hour infusion
Treatment of anaplastic thyroid carcinoma with paclitaxel: Phase 2 trial using ninety-six-hour infusion
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DOI：
10.1089/thy.2000.10.587
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发表时间：
2000-07-01
期刊：
影响因子：
6.6
通讯作者：
DeSimone, PA
中科院分区：
文献类型：
--
作者：
Ain, KB;Egorin, MJ;DeSimone, PA
甲状腺间变性癌是一种罕见的致死性疾病，目前尚无有效的全身治疗方法。临床前研究证实紫杉醇具有抗肿瘤活性。这促使了一项前瞻性2期临床试验，以确定紫杉醇对持续性或转移性甲状腺癌患者的活性，尽管手术或局部放疗。20例患者进入12个研究点中的6个，每3周连续输注96小时紫杉醇，持续1至6个周期；前7例患者每96小时接受120 mg/m(2)，其余患者每96小时接受140 mg/m(2)。由于该肿瘤的生长速度极快，使用改进的标准评估对治疗的总反应，反应持久性在2周或更长时间内是可接受的。取血浆样本进行药代动力学分析。方案外的数据显示，9例患者随后每周输注225mg /m(2)紫杉醇1小时。19例可评估患者表现出53%的总缓解率（95%置信区间，29%-76%），1例完全缓解和9例部分缓解（包括一次性方案）。历史结果。非方案审查显示，7例患者中有2例先前对96小时输注有部分反应，随后对每周治疗有部分反应，2例先前无反应的患者中有1例对每周治疗有部分反应。96小时输注未见大于2级的毒性，而周周输注最常见的是周围神经病变（高达3级）。紫杉醇似乎是唯一一种对甲状腺间变性癌具有显著临床全身活性的药物；然而，它不能改变这种恶性肿瘤的致命性，这表明需要进一步的治疗创新。减少紫杉醇输注之间的时间间隔可能更有效。
Anaplastic thyroid carcinoma is a rare, lethal disease with no effective systemic therapies. Preclinical studies demonstrated antineoplastic activity of paclitaxel. This prompted a prospective phase 2 clinical, trial to determine activity of paclitaxel against anaplastic thyroid carcinoma in patients with persistent or metastatic disease despite surgery or local radiation therapy. Twenty patients, entered through 6 of 12 study sites, were treated with 96-hour continuous infusion paclitaxel every 3 weeks for 1 to 6 cycles; the first 7 patients received 120 mg/m(2) per 96 hours and the rest received 140 mg/m(2) per 96 hours. Total responses to therapy were assessed using modified criteria with response durability acceptable at 2 or more weeks, due to the exceedingly rapid growth rate of this tumor. Plasma samples were obtained for pharmacokinetic analyses. Off-protocol, data showed that 9 patients were later treated with 225 mg/m(2) paclitaxel as weekly 1-hour infusions. Nineteen evaluable patients demonstrated a 53% total response rate (95% confidence interval, 29%-76%) with one complete response and nine partial responses (including one off protocol). Results of historical. review off-protocol showed 2 of 7 patients, with prior partial responses to the 96-hour infusion, had subsequent partial responses to weekly treatment and 1 of 2 prior nonresponders gained a partial response to weekly therapy. No toxicities greater than grade 2 were seen with 96-hour infusions, while peripheral neuropathy (up to grade 3) was most common with postprotocol weekly infusions. Paclitaxel appears to be the only agent with significant clinical systemic activity against anaplastic thyroid carcinoma; however, it is not capable of altering the lethality of this malignancy, suggesting the need for additional therapeutic innovations. Decreased time intervals between paclitaxel infusions may be more efficacious.