Carmichael J, Fink U, Russell R C, Spittle M F, Harris A L, Spiessi G, Blatter J
ICRF Clinical Oncology Unit, Churchill Hospital, Oxford, UK.
Br J Cancer. 1996 Jan;73(1):101-5. doi: 10.1038/bjc.1996.18.
The efficacy and safety of gemcitabine at a starting dose of 800 mg m2 administered once a week for 3 weeks with 1 week's rest was investigated in chemonaive patients with advanced and/or metastatic pancreatic cancer. Of 34 patients, 32 were evaluable for efficacy, 20 patients had metastatic stage IV disease, 25 had a performance status of 1 and 26 (76%) patients has significant pain on presentation. All responses were independently validated by an external oncology review board: two patients achieved a partial response that lasted 5.8 and 5.2 months (6.3%) and six patients were stable for at least 4 weeks. The median duration of survival for evaluable patients was 6.3 months (range 1.6-19.2 months). The tumour markers, CEA, CA 19-9 and CA 195 were serially measured in 16 patients. There was a good correlation with tumour response when all three markers were significantly decreased. In 4 of 16 patients, tumour marker levels decreased by > or = 60%, including the two responders, one patient who survived for 12 months and one patient who showed objective tumour shrinkage but was deemed ineligible for response evaluation because the disease was considered not to be bidimensionally measurable. Symptomatic benefits included improvement in performance status (17.2%), analgesic requirement (7.4%), pain score (28.6%) and nausea (27.3%). The mean number of cycles administered was 2.5 and the mean dosage received was 890 mg m2 per injection. Seventy-four per cent of dose administrations were given on schedule. Toxicity, particularly haematological toxicity, reported as the maximum WHO grade experienced by patients was mild. Infective episodes were rare and limited to WHO grade 2 (6.7%). Nausea and vomiting was generally modest (WHO grade 3, 26.7%). Other side-effects included mild transient flu-like symptoms (seven patients) and peripheral oedema (three patients), which was not associated with abnormal cardiac hepatic or renal function. Gemcitabine has modest activity in pancreatic cancer, a limited positive improvement on a range of patient benefit parameters and has a mild toxicity profile. For these reasons and because of its novel mode of action, gemcitabine warrants further investigation in combination studies in pancreatic cancer.
在初治的晚期和/或转移性胰腺癌患者中，研究了吉西他滨起始剂量为800mg/m²、每周给药1次、共3周、休息1周的疗效和安全性。34例患者中，32例可评估疗效，20例为IV期转移性疾病，25例体能状态为1，26例（76%）患者就诊时伴有明显疼痛。所有反应均由外部肿瘤学审查委员会独立验证：2例患者获得部分缓解，持续时间分别为5.8个月和5.2个月（6.3%），6例患者病情稳定至少4周。可评估患者的中位生存期为6.3个月（范围1.6 - 19.2个月）。对16例患者连续检测肿瘤标志物CEA、CA 19 - 9和CA 195。当所有三种标志物均显著下降时，与肿瘤反应有良好相关性。16例患者中有4例肿瘤标志物水平下降≥60%，包括2例缓解者、1例存活12个月的患者和1例肿瘤出现客观缩小但因疾病被认为不可二维测量而被判定不适合进行反应评估的患者。症状改善包括体能状态改善（17.2%）、镇痛需求改善（7.4%）、疼痛评分改善（28.6%）和恶心改善（27.3%）。平均给药周期数为2.5个，平均每次注射剂量为890mg/m²。74%的剂量按计划给药。报告的毒性，尤其是血液学毒性，以患者经历的最高WHO分级计为轻度。感染性发作罕见，仅限于WHO 2级（6.7%）。恶心和呕吐一般较轻（WHO 3级，26.7%）。其他副作用包括轻度短暂的流感样症状（7例患者）和外周水肿（3例患者），外周水肿与心脏、肝脏或肾脏功能异常无关。吉西他滨在胰腺癌中有一定活性，对一系列患者获益参数有有限的正向改善，且毒性较轻。基于这些原因，并因其独特的作用方式，吉西他滨值得在胰腺癌联合研究中进一步探究。
