Grem J L
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Semin Oncol. 1991 Feb;18(1 Suppl 1):17-26.
Fluorouracil (5-FU) is still the mainstay of adjuvant treatment for colorectal cancer. Two trials have shown a disease-free and overall survival benefit for 5-FU combined with levamisole in patients with node-positive colon cancer. This regimen is fairly well tolerated and devoid of long-term sequelae, and is now considered standard treatment for node-positive colon cancer. One trial showed a modest improvement in disease-free survival for the semustine/vincristine/5-FU combination; the leukemogenicity and renal toxicity caused by semustine have prevented this regimen from being adopted. Although administering 5-FU directly into the portal vein may improve disease-free survival, most trials have failed to demonstrate a reduction in the incidence of hepatic metastases. This technique, therefore, remains investigational. Several trials in rectal cancer show an advantage for 5-FU combined with semustine and radiation therapy in terms of disease-free survival, overall survival, or both; the contribution of semustine has been questioned and is currently being investigated. In patients with metastatic disease, hepatic arterial infusion of floxuridine produces a higher objective response rate than intravenous administration, but has not resulted in a survival benefit; hepatobiliary toxicity limits the duration of therapy. Biochemical modulation of 5-FU with leucovorin increases the response rate produced by 5-FU alone; a survival benefit has also been observed. N-(phosphonacetyl)-L-aspartate has shown initial promise in combination with high-dose 5-FU infusions. Among the many new drugs tested, only tauromustine seems worthy of further study.
氟尿嘧啶(5-FU)仍然是结直肠癌辅助治疗的主要药物。两项试验表明,5-FU联合左旋咪唑对淋巴结阳性结肠癌患者有无病生存和总生存获益。该方案耐受性良好且无长期后遗症,现被认为是淋巴结阳性结肠癌的标准治疗方案。一项试验显示司莫司汀/长春新碱/5-FU联合方案在无病生存方面有适度改善;司莫司汀引起的致白血病性和肾毒性使该方案未被采用。尽管将5-FU直接注入门静脉可能改善无病生存,但大多数试验未能证明肝转移发生率降低。因此,该技术仍处于研究阶段。几项直肠癌试验表明,5-FU联合司莫司汀和放疗在无病生存、总生存或两者方面有优势;司莫司汀的作用受到质疑,目前正在研究中。在转移性疾病患者中,肝动脉灌注氟尿苷产生的客观缓解率高于静脉给药,但未带来生存获益;肝胆毒性限制了治疗持续时间。亚叶酸对5-FU进行生化调节可提高5-FU单独使用时产生的缓解率;也观察到了生存获益。N-(磷酰乙酰基)-L-天冬氨酸与高剂量5-FU输注联合使用已显示出初步前景。在众多测试的新药中,只有牛磺莫司汀似乎值得进一步研究。