Krook J E, Moertel C G, Gunderson L L, Wieand H S, Collins R T, Beart R W, Kubista T P, Poon M A, Meyers W C, Mailliard J A
Duluth Community Clinical Oncology Program, Minn.
N Engl J Med. 1991 Mar 14;324(11):709-15. doi: 10.1056/NEJM199103143241101.
Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone.
Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU).
After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups.
The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis, as compared with postoperative radiation alone.
放射治疗作为直肠癌手术的辅助治疗手段，已被证明可降低局部复发率，但未提高生存率。在先前的一项研究中，与单纯手术相比，放化疗联合显著提高了生存率，但与许多人视为标准治疗的辅助放疗相比则不然。我们设计了一种联合方案，以优化化疗的作用，降低复发率，并与单纯辅助放疗相比提高生存率。
204例直肠癌患者，肿瘤为深度浸润或区域淋巴结转移，被随机分为单纯术后放疗组（4500至5040厘戈瑞）或放疗加氟尿嘧啶组，氟尿嘧啶前后均加用氟尿嘧啶加司莫司汀（甲基环己亚硝脲）的全身治疗周期。
中位随访超过7年后，联合治疗使直肠癌复发率降低了34%（P = 0.0016；95%置信区间，12%至50%）。初始局部复发率降低了46%（P = 0.036；95%置信区间，2%至70%），远处转移率降低了37%（P = 0.011；95%置信区间，9%至57%）。此外，联合治疗使癌症相关死亡率降低了36%（P = 0.0071；95%置信区间，14%至53%），总死亡率降低了29%（P = 0.025；95%置信区间，7%至45%）。其急性毒性作用包括恶心、呕吐、腹泻、白细胞减少和血小板减少。这些作用很少严重。严重的、延迟的治疗相关反应，通常是需要手术的小肠梗阻，在所有接受放疗的患者中发生率为6.7%，且两个治疗组这些并发症的发生率相当。
与单纯术后放疗相比，术后局部放疗加氟尿嘧啶与基于氟尿嘧啶方案的全身治疗联合，显著且实质性地改善了预后不良的直肠癌的治疗效果。
