Miller R C, Martenson J A, Sargent D J, Kahn M J, Krook J E
Division of Radiation Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Int J Radiat Oncol Biol Phys. 1998 Jun 1;41(3):593-8. doi: 10.1016/s0360-3016(98)00084-4.
The combination of pelvic radiotherapy and 5-fluorouracil-based chemotherapy is associated with an increase in acute gastrointestinal toxicity during rectal adjuvant therapy, most notably an increased incidence of diarrhea. Previous randomized, prospective studies have limited their analysis to presenting rates of severe and life-threatening diarrhea (Grade 3 or greater), and few data are available detailing the extent of mild to moderate diarrhea. To provide baseline data for future studies, we conducted a detailed analysis of diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer.
In a multiinstitutional clinical trial, 204 eligible patients with rectal carcinoma that either was deeply invasive (T3-T4) or involved regional lymph nodes were randomized to receive either postoperative pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5-fluorouracil-based chemotherapy. Toxicity was assessed prospectively.
For the 99 eligible patients who received pelvic radiotherapy alone, rates of Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%, respectively. For the 96 eligible patients who received radiotherapy and 5-fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34, 23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant rectal therapy were manifested across all toxicity levels for patients receiving chemotherapy and pelvic radiotherapy. Of primary clinical importance is the substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22 vs. 4%,p = 0.001) Additionally, increased rates of any diarrhea and also severe or life-threatening diarrhea were observed in patients who had a low anterior resection compared with those who had an abdominoperineal resection (p < 0.001 and p = 0.006, respectively).
These results will be of value as a baseline for investigators who want to use treatment toxicity as an end point in cancer control or cancer therapy trials utilizing similar treatment techniques. Patients receiving 5-fluorouracil and pelvic radiotherapy compared with patients receiving pelvic radiotherapy alone and patients with a prior history of a low anterior resection compared with patients who had a prior history of an abdominoperineal resection experienced increased rates of Grades 1 through 4 acute treatment-related diarrhea, and the most important increase occurred as Grade 3 toxicity.
盆腔放疗与基于5-氟尿嘧啶的化疗联合应用于直肠癌辅助治疗时，会增加急性胃肠道毒性，最显著的是腹泻发生率升高。既往的随机前瞻性研究仅分析了严重及危及生命的腹泻（3级或更高级别）发生率，而关于轻度至中度腹泻程度的详细数据较少。为了为未来研究提供基线数据，我们对一项既往直肠癌辅助治疗临床试验中的腹泻情况进行了详细分析。
在一项多机构临床试验中，204例符合条件的直肠癌患者（肿瘤为深度浸润性（T3 - T4）或累及区域淋巴结）被随机分为两组，一组仅接受术后盆腔放疗（45至50.4 Gy）；另一组接受盆腔放疗及推注式基于5-氟尿嘧啶的化疗。前瞻性评估毒性反应。
在仅接受盆腔放疗的99例符合条件的患者中，治疗期间0级、1级、2级、3级和4级腹泻的发生率分别为59%、20%、17%、4%和0%。在接受放疗及5-氟尿嘧啶治疗的96例符合条件的患者中，0级、1级、2级、3级和4级腹泻的总体发生率分别为21%、34%、23%、20%和2%。接受化疗及盆腔放疗的患者在辅助性直肠治疗期间腹泻发生率的增加在所有毒性级别均有体现。主要临床意义在于严重或危及生命的腹泻（3级或更高级别）显著增加（22%对4%，p = 0.001）。此外，与经腹会阴联合切除术患者相比，低位前切除术患者的任何腹泻以及严重或危及生命的腹泻发生率也有所增加（分别为p < 0.001和p = 0.006）。
对于那些希望在利用类似治疗技术的癌症控制或癌症治疗试验中，将治疗毒性作为终点的研究人员而言，这些结果可作为基线参考。与仅接受盆腔放疗的患者相比，接受5-氟尿嘧啶及盆腔放疗的患者，以及与有经腹会阴联合切除术病史的患者相比，有低位前切除术病史的患者1至4级急性治疗相关腹泻的发生率增加，且最重要的是3级毒性腹泻发生率增加。
