Hainsworth J D, Raefsky E L, Greco F A
Sarah Cannon Cancer Center, Centennial Medical Center, Nashville, Tennessee 37203, USA.
Cancer J Sci Am. 1995 Nov-Dec;1(4):281-7.
Paclitaxel is currently administered by prolonged intravenous infusion primarily because of severe hypersensitivity reactions that occurred with rapid infusions during early clinical trails. This phase I-II study evaluates the feasibility of 1-hour paclitaxel administration and compares the toxicity and efficacy of two different 1-hour infusion schedules.
One hundred sixty-four patients with advanced, refractory cancer were randomized to receive one of two paclitaxel schedules: a 1-hour infusion or a 3-day, divided dose schedule, each daily dose administered by 1-hour infusion. The first 60 patients received a total paclitaxel dose of 135 mg/m2, and the remaining 104 patients received 200 mg/m2. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Cytokines were not routinely used.
No serious hypersensitivity reactions occurred in 620 courses of paclitaxel. Both doses were well tolerated; grade 3 or 4 leukopenia was produced in 22% of courses at 135 mg/m2 and 23% of courses at 200 mg/m2. Both schedules were well tolerated, but grade 3 and 4 leukopenia was more common with the 3-day schedule when paclitaxel 200 mg/m2 was administered. Myalagias were more common with the 1-day schedule. Major responses occurred in 35 of 153 evaluable patients (23%). Response rates in ovarian, breast, and non-small cell lung cancer were 45%, 33%, and 25%, respectively. At the 200 mg/m2 dose, 11 of 36 patients (31%) with non-small cell lung cancer responded, including 6 of 16 who had received previous chemotherapy. No major difference in response rates was observed when the 1-day and 3-day schedules were compared.
Paclitaxel can be safely administered by 1-hour infusion in an outpatient setting. A dose of 200 mg/m2 is well tolerated without the use of cytokines. Both schedules are well tolerated; however, the 3-day schedule produces more leukopenia when a 200 mg/m2 dose is administered. Antitumor activity was seen with both doses and schedules. Administration of paclitaxel over 1-hour is less toxic, easier, and less expensive than are prolonged infusions, and deserves continued investigation.
目前紫杉醇主要通过长时间静脉输注给药，这主要是因为在早期临床试验中快速输注时会发生严重的过敏反应。这项I-II期研究评估了1小时输注紫杉醇的可行性，并比较了两种不同的1小时输注方案的毒性和疗效。
164例晚期难治性癌症患者被随机分配接受两种紫杉醇方案之一：1小时输注或3天分次给药方案，每天剂量均通过1小时输注给药。前60例患者接受的紫杉醇总剂量为135mg/m²，其余104例患者接受200mg/m²。所有患者均接受地塞米松、苯海拉明和西咪替丁预处理。未常规使用细胞因子。
在620个紫杉醇疗程中未发生严重过敏反应。两种剂量的耐受性均良好；135mg/m²剂量组22%的疗程出现3级或4级白细胞减少，200mg/m²剂量组23%的疗程出现3级或4级白细胞减少。两种方案的耐受性均良好，但在给予200mg/m²紫杉醇时，3天方案的3级和4级白细胞减少更为常见。1天方案的肌肉痛更为常见。153例可评估患者中有35例（23%）出现主要缓解。卵巢癌、乳腺癌和非小细胞肺癌的缓解率分别为45%、33%和25%。在200mg/m²剂量组中，36例非小细胞肺癌患者中有11例（31%）有反应，其中16例接受过先前化疗的患者中有6例有反应。比较1天和3天方案时，未观察到缓解率有重大差异。
紫杉醇可以在门诊环境中通过1小时输注安全给药。200mg/m²的剂量在不使用细胞因子的情况下耐受性良好。两种方案的耐受性均良好；然而，在给予200mg/m²剂量时，3天方案会产生更多的白细胞减少。两种剂量和方案均显示出抗肿瘤活性。与长时间输注相比，1小时输注紫杉醇毒性更小、更简便且成本更低，值得继续研究。
