Kuzel T M, Tallman M S, Shevrin D, Braud E, Kilton L, Johnson P, Kozlowski J, Vogelzang N J, Blough R, Benson A B
Illinois Cancer Center, Chicago.
Cancer. 1993 Sep 15;72(6):1965-8. doi: 10.1002/1097-0142(19930915)72:6<1965::aid-cncr2820720629>3.0.co;2-x.
5-Fluorouracil (5-FU) has been previously associated with therapeutic benefit in hormone refractory prostate cancer. However, no previous study has administered 5-FU as a prolonged continuous infusion, which may be the optimal schedule for this cell-cycle specific agent.
Therefore, 25 patients were treated with 5-FU administered as a continuous intravenous infusion at a dose of 1000 mg/m2/day for 5 days every 28 days. Eligibility required disease defined by bidimensionally measurable lesions or evaluable lesions on bone scan or radiograph with elevated serum levels of prostate-specific antigen (PSA), no severe cytopenias, and an Eastern Cooperative Oncology Group performance status less than 3. Prior chemotherapy was not allowed. Dose modifications were specified for mucositis and hematologic toxicity.
Eighteen of 22 patients were evaluable for response and toxicity, whereas 4 were evaluable for toxicity alone. Toxicity was significant using this dose and schedule and included episodes of sudden death (one patient), paroxysmal supraventricular tachycardia (one patient), and congestive heart failure (one patient). Other Grade 3 toxicities included stomatitis (two patients) and diarrhea (one patient). Significant myelosuppression did not occur. Objective responses were not observed, but 12 patients experienced stable disease with a median duration of 4 months.
Infusional 5-FU can not be recommended for the treatment of advanced hormone refractory prostate cancer.
5-氟尿嘧啶(5-FU)先前已被证明对激素难治性前列腺癌具有治疗益处。然而,此前尚无研究采用延长持续输注的方式给予5-FU,而这可能是这种细胞周期特异性药物的最佳给药方案。
因此,25例患者接受5-FU治疗,以1000 mg/m²/天的剂量持续静脉输注,每28天进行5天。入选标准要求疾病通过二维可测量病变或骨扫描或X光片上可评估病变定义,且血清前列腺特异性抗原(PSA)水平升高,无严重血细胞减少,东部肿瘤协作组(ECOG)体能状态评分小于3。不允许有先前化疗史。针对黏膜炎和血液学毒性制定了剂量调整方案。
22例患者中有18例可评估疗效和毒性,4例仅可评估毒性。采用此剂量和方案时毒性显著,包括猝死(1例患者)、阵发性室上性心动过速(1例患者)和充血性心力衰竭(1例患者)。其他3级毒性包括口腔炎(2例患者)和腹泻(1例患者)。未发生显著的骨髓抑制。未观察到客观缓解,但12例患者病情稳定,中位持续时间为4个月。
不推荐使用输注性5-FU治疗晚期激素难治性前列腺癌。