EFFECTIVE SURGICAL ADJUVANT THERAPY FOR HIGH-RISK RECTAL-CARCINOMA
EFFECTIVE SURGICAL ADJUVANT THERAPY FOR HIGH-RISK RECTAL-CARCINOMA
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DOI：
10.1056/nejm199103143241101
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发表时间：
1991-03-14
影响因子：
158.5
通讯作者：
VIDYARTHI, SC
中科院分区：
文献类型：
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作者：
KROOK, JE;MOERTEL, CG;VIDYARTHI, SC
背景放射治疗作为直肠癌手术的辅助治疗已被证明可以减少局部复发，但不能提高生存率。在先前的研究中，与单独手术相比，联合放疗和化疗显著提高了生存率，但与许多人认为是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，与单纯辅助放疗相比，优化了化疗的作用，降低了复发率，提高了生存率。204例直肠癌患者，无论是深度浸润还是区域淋巴结转移，均随机分为术后单纯放疗组（4500 ~ 5040 cGy）或放疗加氟尿嘧啶组，放疗前后均给予氟尿嘧啶加司莫司汀（methyl-CCNU）系统治疗。在中位随访超过7年后，联合治疗使直肠癌复发率降低了34%（P = 0.0016; 95%置信区间为12%至50%）。初始局部复发减少了46%（P = 0.036; 95%置信区间，2%至70%），远处转移减少了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%）。其急性毒性反应包括恶心、呕吐、腹泻、白细胞减少和血小板减少。这些影响很少严重。严重的、延迟的治疗相关反应，通常是需要手术的小肠梗阻，发生在所有接受放射治疗的患者中的6.7%，这些并发症的发生率在两个治疗组中相当。与术后单纯放疗相比，术后局部放疗加氟尿嘧啶和以氟尿嘧啶为基础的全身治疗方案的联合应用显著且实质性地改善了预后不良的直肠癌的治疗结果。
Background. 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.Methods. 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).Results. 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 severs. 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.Conclusions. 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.