Beck T M
Mountain States Tumor Institute, Boise, ID 82712-6297.
Semin Oncol. 1992 Dec;19(6 Suppl 15):20-5.
The selective 5-hydroxytryptamine3 antagonist ondansetron has been shown to be effective in preventing nausea and vomiting associated with highly emetogenic cisplatin chemotherapy. Two multicenter, placebo-controlled, dose-comparison studies (S3A-361 and S3A-362) were undertaken to investigate the efficacy and safety of oral ondansetron in patients receiving non-cisplatin, cyclophosphamide-based regimens in the outpatient setting. Chemotherapy-naive patients undergoing their first cycle of cyclophosphamide-based (> or = 500 mg/m2) chemotherapy were randomized to receive placebo or ondansetron, 1, 4, or 8 mg, three times per day for 3 days. In addition to cyclophosphamide, all patients received doxorubicin, methotrexate, or another low-to-moderately emetogenic agent. In study S3A-361, 318 of 349 patients were evaluable for efficacy; 297 of 324 patients in study S3A-362 were evaluable for efficacy. All patients in both studies were evaluable for safety. All ondansetron groups were superior to placebo groups in both studies for all measured efficacy parameters. In the two studies combined, 14%, 47%, 65%, and 66% of patients in the placebo, 1-, 4-, and 8-mg ondansetron groups, respectively, experienced no emetic episodes. The rate of therapeutic failure was statistically lower in the ondansetron groups in both studies compared with the placebo groups. In addition, therapeutic failure decreased in a dose-dependent manner. Severity of nausea, food intake, time to first emetic episode, and need for rescue antiemetics were also improved for the ondansetron groups. When the patients were stratified for doxorubicin-containing regimens, those patients receiving doxorubicin had a lower response rate with placebo and ondansetron than those on non-doxorubicin regimens. However, a dose-related improvement in efficacy was still observed with ondansetron in this subset of patients. In patients receiving the more emetogenic high-dose cyclophosphamide (> or = 600 mg/m2) regimens, a dose-related improvement in efficacy also was observed. In conclusion, oral ondansetron was found to be an effective and safe antiemetic for patients receiving cyclophosphamide-based chemotherapy in the outpatient setting. The 8-mg dose was optimal, particularly in patients receiving doxorubicin-containing or high-dose cyclophosphamide regimens.
选择性5-羟色胺3拮抗剂昂丹司琼已被证明可有效预防与高致吐性顺铂化疗相关的恶心和呕吐。开展了两项多中心、安慰剂对照、剂量比较研究（S3A-361和S3A-362），以调查口服昂丹司琼在门诊接受非顺铂、基于环磷酰胺方案治疗的患者中的疗效和安全性。初次接受化疗的患者在接受首个基于环磷酰胺（≥500mg/m²）的化疗周期时，被随机分配接受安慰剂或1、4或8mg昂丹司琼，每日3次，共3天。除环磷酰胺外，所有患者还接受了阿霉素、甲氨蝶呤或另一种低至中度致吐药物。在研究S3A-361中，349例患者中有318例可进行疗效评估；在研究S3A-362中，324例患者中有297例可进行疗效评估。两项研究中的所有患者均可进行安全性评估。在两项研究中，所有测量的疗效参数方面，所有昂丹司琼组均优于安慰剂组。两项研究合并后，安慰剂组、1mg、4mg和8mg昂丹司琼组分别有14%、47%、65%和66%的患者未发生呕吐发作。两项研究中，昂丹司琼组的治疗失败率在统计学上低于安慰剂组。此外，治疗失败率呈剂量依赖性降低。昂丹司琼组的恶心严重程度、食物摄入量、首次呕吐发作时间以及使用急救止吐药的需求也有所改善。当根据含阿霉素方案对患者进行分层时，接受阿霉素治疗的患者使用安慰剂和昂丹司琼的缓解率低于接受非阿霉素方案治疗的患者。然而，在这部分患者中，仍观察到昂丹司琼疗效呈剂量相关改善。在接受更高致吐性高剂量环磷酰胺（≥600mg/m²）方案治疗的患者中，也观察到疗效呈剂量相关改善。总之，对于门诊接受基于环磷酰胺化疗的患者，口服昂丹司琼被发现是一种有效且安全的止吐药。8mg剂量是最佳剂量，尤其在接受含阿霉素方案或高剂量环磷酰胺方案治疗的患者中。
