Sandler A B, Kindler H L, Einhorn L H, Mitchell E, Masters G, Kraut M, Nicol S, Raghavan D
Department of Medicine, Indiana University, Indianapolis, USA.
Ann Oncol. 2000 Sep;11(9):1161-4. doi: 10.1023/a:1008369718242.
There were approximately 12,500 cases of esophageal carcinoma diagnosed in the US in 1992 and 12,200 deaths. The impact of chemotherapy on patients with metastatic disease is marginal with a median survival of only five months. Gemcitabine (LY188011,2,2,-difluorodeoxycytidine: dFdC), an analog of cytosine arabinoside (ara-C), is a pyrimidine antimetabolite. Gemcitabine has shown interesting clinical activity in initial phase II clinical trials in a variety of malignancies, including the aerodigestive malignancies, squamous-cell carcinoma of the head/neck and both non-small-cell and small-cell lung cancer.
A total of 21 patients with chemotherapy-naïve metastatic esophageal carcinoma were entered. Nineteen patients were evaluable for toxicity and seventeen patients were evaluable for response. Gemcitabine was administered intravenously at 1250 mg/m2 over 30-60 minutes on days 1, 8, and 15 followed by 1 week of rest. This four-week schedule defined a cycle of treatment. Patients may have received a maximum of six cycles.
Gemcitabine was well tolerated with minimal non-hematologic toxicity and grade 3-4 anemia, granulocytopenia, and thrombocytopenia occurring in 10.5%, 21%, and 0% of patients, respectively. No responses were seen in the seventeen evaluable patients.
At the dose and schedule studied it would appear that gemcitabine has no activity in patients with chemotherapy-naïve esophageal carcinoma.
1992年美国约有12,500例食管癌确诊病例，12,200例死亡病例。化疗对转移性疾病患者的影响有限，中位生存期仅为5个月。吉西他滨（LY188011，2,2 - 二氟脱氧胞苷：dFdC）是阿糖胞苷（ara - C）的类似物，属于嘧啶抗代谢物。在包括气消化道恶性肿瘤、头颈部鳞状细胞癌以及非小细胞肺癌和小细胞肺癌在内的多种恶性肿瘤的初始II期临床试验中，吉西他滨已显示出有趣的临床活性。
共纳入21例未经化疗的转移性食管癌患者。19例患者可评估毒性，17例患者可评估疗效。在第1、8和15天，吉西他滨以1250mg/m²的剂量静脉输注30 - 60分钟，随后休息1周。这个四周的疗程定义为一个治疗周期。患者最多可接受六个周期的治疗。
吉西他滨耐受性良好，非血液学毒性极小，3 - 4级贫血、粒细胞减少和血小板减少分别发生在10.5%、21%和0%的患者中。17例可评估疗效的患者均未出现缓解。
在所研究的剂量和疗程下，吉西他滨对未经化疗的食管癌患者似乎没有活性。
