Figlin R A, Abi-Aad A S, Belldegrun A, deKernion J B
Department of Medicine, University of California-Los Angeles School of Medicine 90024-1738.
Semin Oncol. 1991 Oct;18(5 Suppl 7):102-7.
Approximately 24,000 cases of renal cell carcinoma are expected in the United States in 1990. Although approximately 50% of patients with local disease are cured by surgery, in patients with metastatic disease the median survival is only approximately 10 months. Neither chemotherapy nor radiation therapy has been shown to be effective against metastatic renal cell carcinoma. Immunotherapy has come to the forefront of clinical research for the treatment of metastatic renal cell carcinoma. In the past decade, the development of recombinant DNA techniques has enabled the production of large quantities of biologic response modifiers such as the interferons and interleukins. Following initial reports in 1983 by the University of California-Los Angeles (UCLA) group and the investigators at M. D. Anderson Hospital, in Houston, TX, numerous trials have demonstrated a reproducible objective response rate to interferon of 15% to 20%. These responses are independent of the interferon preparation used, and optimal dosage/schedule has not been determined. In general, responses have been correlated with the following patient factors: previous nephrectomy, good performance status, a long disease-free interval, and lung-predominant disease. Median response durations of from 8 to 10 months can be expected. The addition of vinblastine, gamma-interferon, or aspirin has not improved the therapeutic index. Interleukin-2 therapy has produced encouraging results in 10% to 15% of patients. Although high-dose therapy is associated with substantive side effects, a small cohort of patients have been in continuous remission for extended periods of time, raising the possibility of "true" complete remissions of clinical significance. Recent trials, including our trials at UCLA, have combined the interleukins and interferons in this patient population. This combination has a sound scientific basis and the results are encouraging, especially when the toxicity profile is considered. Most patients receive these combinations as outpatients and have not required hospitalization nor suffered the toxicities of the high-dosage regimens. Complete pathologic remissions have been observed using this lower dosage, outpatient schedule. Clinical trials suggest that interferon and interleukin-2 may have an expanding role in metastatic kidney cancer both as single agents and in combination outpatient biologic therapy. The future clinical trials of kidney cancer will continue to incorporate these biologic response modifiers into the therapeutic strategies of the 1990s.
1990年，美国预计将出现约24000例肾细胞癌病例。尽管约50%的局部疾病患者可通过手术治愈，但转移性疾病患者的中位生存期仅约为10个月。化疗和放疗均未显示对转移性肾细胞癌有效。免疫疗法已成为转移性肾细胞癌临床研究的前沿领域。在过去十年中，重组DNA技术的发展使得能够大量生产生物反应调节剂，如干扰素和白细胞介素。1983年加利福尼亚大学洛杉矶分校（UCLA）研究小组以及德克萨斯州休斯顿市MD安德森医院的研究人员首次发表报告后，众多试验证明，干扰素的客观缓解率可重复性地达到15%至20%。这些缓解与所使用的干扰素制剂无关，且尚未确定最佳剂量/疗程。一般来说，缓解与以下患者因素相关：既往肾切除术、良好的身体状况、较长的无病间期以及以肺部为主的疾病。预计中位缓解持续时间为8至10个月。加入长春碱、γ干扰素或阿司匹林并未提高治疗指数。白细胞介素-2疗法在10%至15%的患者中取得了令人鼓舞的结果。尽管高剂量疗法伴有大量副作用，但一小部分患者已长期持续缓解，这增加了出现具有临床意义的“真正”完全缓解的可能性。最近的试验，包括我们在UCLA进行的试验，在这类患者中联合使用了白细胞介素和干扰素。这种联合有坚实的科学依据，结果令人鼓舞，尤其是考虑到毒性特征时。大多数患者作为门诊患者接受这些联合治疗，无需住院，也未遭受高剂量方案的毒性反应。使用这种低剂量门诊方案已观察到完全病理缓解。临床试验表明，干扰素和白细胞介素-2在转移性肾癌中作为单一药物以及联合门诊生物治疗可能发挥越来越重要的作用。未来的肾癌临床试验将继续把这些生物反应调节剂纳入20世纪90年代的治疗策略中。
