PHASE-II STUDY OF GEMCITABINE (2',2'-DIFLUORODEOXYCYTIDINE) IN PREVIOUSLY TREATED OVARIAN-CANCER PATIENTS
PHASE-II STUDY OF GEMCITABINE (2',2'-DIFLUORODEOXYCYTIDINE) IN PREVIOUSLY TREATED OVARIAN-CANCER PATIENTS
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DOI：
10.1093/jnci/86.20.1530
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发表时间：
1994-10-19
期刊：
影响因子：
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通讯作者：
NEIJT, JP
中科院分区：
文献类型：
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作者：
LUND, B;HANSEN, OP;NEIJT, JP
背景：含铂联合化疗提高了晚期卵巢癌患者的生存率，但大多数患者仍然死于疾病。因此，开发新的无交叉耐药药物非常重要。吉西他滨（2′，2′-二氟脱氧胞苷）在体外肿瘤细胞培养和动物肿瘤模型中显示出广谱的抗肿瘤活性。临床活动也已报道在各种实体瘤类型。目的：我们的目的是评估吉西他滨在先前治疗过的卵巢癌患者中的临床活性，并进一步表征该化合物的毒性。方法：吉西他滨（800 mg/m(2)）静脉滴注，每周1次，连续3周，休息1周。最多允许两种不同的先前治疗方案。每隔一个疗程通过盆腔检查和/或超声和计算机断层扫描评估疗效。结果：50例患者符合条件；35例（70%）肿瘤体积较大（肿瘤直径大于5cm）。所有患者既往均接受含铂联合化疗。42例患者可评估反应。42例患者中有8例（19%）（95%可信区间= 9%-34%）获得部分缓解，中位缓解持续时间为8.1个月（范围4.4-12.5个月）。所有应答者在治疗前6个月内开始使用吉西他滨治疗，8名应答者中有7名对一线含铂联合化疗耐药。总体中位进展时间为2.8个月（范围0.2-12.5个月），总体中位生存期为6.2个月（范围0.2-26.0个月）。48例患者可评估毒性。白细胞减少和血小板减少是导致剂量减少（分别为27%和14%）和剂量减少（分别为37%和21%）的主要毒性作用。28%的患者出现短暂的轻度流感样综合征，22%的患者出现治疗相关的外周水肿。还观察到1级血尿（53%的患者），1-2级蛋白尿（79%的患者），肝毒性主要为1-2级（59%的患者）。结论：吉西他滨是一种耐受性良好的新药，对铂耐药卵巢癌患者有治疗作用。意义：需要验证性试验，并且应该评估吉西他滨在先前未治疗的患者中的活性。
Background: Platinum-containing combination chemotherapy has resulted in improved survival rates in patients with advanced ovarian carcinoma, but the majority of the patients still die of their disease. It is therefore important to develop new non-cross-resistant drugs. Gemcitabine (2',2'-difluorodeoxycytidine) has shown a broad spectrum of antineoplastic activity in tumor cell cultures in vitro and in animal tumor models. Clinical activity also has been reported in a variety of solid tumor types. Purpose: Our purpose was to assess the clinical activity of gemcitabine in previously treated ovarian cancer patients and to further characterize the toxicity of the compound. Methods: Gemcitabine (800 mg/m(2)) was given intravenously once a week for 3 consecutive weeks, followed by 1 week of rest. A maximum of two different prior treatment regimens was allowed. Response was assessed by pelvic examination and/or ultrasound and computed tomography scans every other course. Results: Fifty patients were eligible; 35 (70%) had bulky disease (tumor greater than 5 cm in diameter). All patients had received prior platinum-containing combination chemotherapy. Forty-two patients were assessable for response. Eight (19%) of the 42 patients (95% confidence interval = 9%-34%) achieved a partial response, with a median response duration of 8.1 months (range, 4.4-12.5 months). All responders started treatment with gemcitabine within 6 months of prior treatment, and seven of the eight responders were resistant to first-line platinum-containing combination chemotherapy. Overall median time to progression was 2.8 months (range, 0.2-12.5 months), and overall median survival was 6.2 months (range, 0.2-26.0 months). Forty-eight patients were assessable for toxicity. Leukocytopenia and thrombocytopenia were the main toxic effects that caused dose omissions (27% and 14%, respectively) and dose reductions (37% and 21%, respectively). A transient mild flu-like syndrome occurred in 28% of the patients, and treatment-related peripheral edema developed in 22%. Grade 1 hematuria (53% of patients), grade 1-2 proteinuria (79% of patients), and liver toxicity that was mostly grade 1-2 (59% of patients) were also observed. Conclusions: Gemcitabine is a well-tolerated new drug with activity in platinum-resistant ovarian cancer patients. Implications: Confirmatory trials are needed, and the activity of gemcitabine in previously untreated patients should be assessed.