Casper E S, Green M R, Kelsen D P, Heelan R T, Brown T D, Flombaum C D, Trochanowski B, Tarassoff P G
Memorial Sloan-Kettering Cancer Center, New York, NY.
Invest New Drugs. 1994;12(1):29-34. doi: 10.1007/BF00873232.
Gemcitabine is a novel nucleoside analog which demonstrated a broad spectrum of preclinical activity in solid tumor models, and responses in patients with pancreas cancer during phase I evaluation. Patients with measurable adenocarcinoma of the pancreas who had received no previous chemotherapy were eligible for this multicenter phase II clinical trial. Gemcitabine 800 mg/m2 was administered intravenously weekly for 3 consecutive weeks, followed by one week rest, every 4 weeks. Forty-four patients entered the trial; 35 had at least 2 cycles of therapy. Partial response was observed in 5 patients (11%, estimated 95% confidence interval 2-20%), with a median duration of 13 months. All responding patients had stabilization or improvement in performance status. Fourteen patients had stable disease of 4 or more months. The median WBC nadir was 3.8 x 10(3)/microliters (range 1.6-9.3) and the median absolute neutrophil (ANC) nadir was 2.0 x 10(3)/microliters (range 0.4-7.2). Thrombocytopenia - 100.0 x 10(3)/microliters was observed in 15 patients; the median platelet nadir was 123.0 (range 30.0-245.0). All patients experienced a mild to moderate flu-like syndrome. In addition, one patient had a mild hemolytic-uremic syndrome which appeared related to gemcitabine therapy. Gemicitabine demonstrated marginal activity in this resistant neoplasm, without excessive toxicity. Further evaluation, including the use of more intense dosing and/or combination therapy, is warranted.
吉西他滨是一种新型核苷类似物，在实体瘤模型中显示出广泛的临床前活性，并在I期评估中使胰腺癌患者产生反应。未曾接受过化疗的可测量胰腺腺癌患者符合这项多中心II期临床试验的条件。吉西他滨800mg/m²静脉注射，每周1次，连续3周，随后休息1周，每4周重复。44例患者进入试验；35例至少接受了2个周期的治疗。5例患者出现部分缓解（11%，估计95%置信区间2-20%），中位缓解持续时间为13个月。所有有反应的患者的体能状态均稳定或改善。14例患者疾病稳定达4个月或更长时间。白细胞计数最低点的中位数为3.8×10³/微升（范围1.6-9.3），绝对中性粒细胞计数最低点的中位数为2.0×10³/微升（范围0.4-7.2）。15例患者出现血小板减少（血小板计数<100.0×10³/微升）；血小板最低点的中位数为123.0（范围30.0-245.0）。所有患者均经历了轻至中度的流感样综合征。此外，1例患者出现轻度溶血尿毒综合征，似乎与吉西他滨治疗有关。吉西他滨在这种难治性肿瘤中显示出一定活性，且无过度毒性。有必要进行进一步评估，包括采用更强的剂量和/或联合治疗。
