STREPTOZOCIN DOXORUBICIN, STREPTOZOCIN FLUOROURACIL, OR CHLOROZOTOCIN IN THE TREATMENT OF ADVANCED ISLET-CELL CARCINOMA
STREPTOZOCIN DOXORUBICIN, STREPTOZOCIN FLUOROURACIL, OR CHLOROZOTOCIN IN THE TREATMENT OF ADVANCED ISLET-CELL CARCINOMA
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DOI：
10.1056/nejm199202203260804
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发表时间：
1992-02-20
影响因子：
158.5
通讯作者：
KLAASSEN, D
中科院分区：
文献类型：
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作者：
MOERTEL, CG;LEFKOPOULO, M;KLAASSEN, D
背景 链脲佐菌素联合氟尿嘧啶已成为晚期胰岛细胞癌的标准治疗方法。然而，阿霉素也被证明对这种类型的肿瘤是有效的，因为有chlorozotocin，一种药物，结构上类似于链脲佐菌素，但不太经常引起呕吐。 在这项多中心试验中，我们将105例晚期胰岛细胞癌患者随机分配接受三种治疗方案之一：链脲佐菌素联合氟尿嘧啶、链脲佐菌素联合阿霉素或单用氯脲佐菌素。31例对治疗无反应的患者交叉使用氯脲佐菌素单药或联合用药。 链脲佐菌素联合多柔比星在客观测量的肿瘤消退率（69% vs. 45%，P = 0.05）和肿瘤进展时间长度（中位数，20 vs. 6.9个月; P = 0.001）方面优于链脲佐菌素联合氟尿嘧啶上级。链脲佐菌素联合阿霉素在生存期方面也有显著优势（中位数，2.2 vs. 1.4年; P = 0.004），当我们考虑长期生存期（> 2年）时，这一优势更为突出。单用氯霉素产生30%的消退率，肿瘤进展时间和生存时间与链脲佐菌素加氟尿嘧啶相当。在单用氯脲霉素或其中一种联合治疗方案失败后进行交叉治疗，总的反应率仅为17%，而且反应是短暂的。所有治疗方案的毒性反应包括呕吐，氯脲佐菌素的毒性反应最轻;血液学抑制;以及长期治疗的肾功能不全。结论. 联合应用链脲佐菌素和阿霉素治疗晚期胰岛细胞癌上级优于目前标准的链脲佐菌素加氟尿嘧啶方案。单用氯霉素与链脲佐菌素加氟尿嘧啶的疗效相似，但其产生的胃肠道副作用比含链脲佐菌素的方案少。因此，它值得作为联合用药方案的一个组成部分进行研究。
Background. The combination of streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to streptozocin but less frequently causes vomiting.Methods. In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: streptozocin plus fluorouracil, streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens.Results. Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also had a significant advantage in terms of survival (median, 2.2 vs. 1.4 years; P = 0.004) that was accentuated when we considered long-term survival (> 2 years). Chlorozotocin alone produced a 30 percent regression rate, with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil. Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent, and the responses were transient. Toxic reactions to all regimens included vomiting, which was least severe with chlorozotocin; hematologic depression; and, with long-term therapy, renal insufficiency. Conclusions. The combination of streptozocin and doxorubicin is superior to the current standard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil, but it produces fewer gastrointestinal side effects than the regimens containing streptozocin. It therefore merits study as a constituent of combination drug regimens.