Ⅱ和Ⅲ期直肠癌术后去氧氟尿苷加四氢叶酸钙同步放化疗的Ⅰ期临床研究

目的 探讨Ⅱ、Ⅲ期直肠癌患者根治术后去氧氟尿苷+四氢叶酸钙同步放化疗中去氧氟尿苷的剂量限制性毒性(DLT)和最大耐受剂量(MTD).方法 术后病理证实为Ⅱ、Ⅲ期的直肠癌患者16例行盆腔放疗5周(总剂量50 Gy分25次),同步口服去氧氟尿苷+四氢叶酸钙30 mg/(m2·d)化疗,从放疗第1天开始,3次/d,连续服用直至放疗结束.去氧氟尿苷DLT的定义为≥3级的血液学或非血液学毒性反应.结果 16例患者分别人去氧氟尿苷450 mg/(m2·d)组3例、550mg/(m2·d)组6例、650 mg/(m2·d)组7例.550 mg/(m2·d)组出现1例DLT(1例4级腹泻),补充3例后未发现DLT,继而进入650 mg/(m2·d)组.该组中第1例因治疗第3周出现3级腹痛拒绝化疗退出研究,随后入组3例中1例先后出现3级腹痛、腹泻、恶心、乏力和2级发热以及白细胞下降,以后再补充的3例均出现了3级腹泻,试验终止于650 mg/(m2·d)组.16例中12例完成预计的去氧氟尿苷+四氢叶酸钙同步放化疗计划,4例终止或中断放化疗者分别为550 mg/(m2·d)组1例和650mg/(m2·d)组3例.DLT主要表现为3级恶心或呕吐(1人次)、腹泻(4人次)、疲劳(1人次)和腹部绞痛(2人次)以及4级腹泻(1人次).结论 Ⅱ、Ⅲ期直肠癌根治术后采用去氧氟尿苷+四氢叶酸钙同步放化疗时,去氧氟尿苷的最大耐受剂量为550 mg/(m2·d); 恶心或呕吐、腹泻、腹部绞痛和疲劳是剂量限制性不良反应,患者耐受性较差.

A phase Ⅰ study of postoperative concurrent radiotherapy and oral doxifluridine and leucovorin for Ⅱ/Ⅲ stage rectal cancer

Objective A phase Ⅰ study was conducted to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity(DLT) of chemotherapy of oral doxifluridine(5-dFUR) and leucovorin with concurrent standard radiotherapy(RT) as adjuvant treatment in patients with rectal cancer. Methods Patients aged 18-75 years old, Karnofsky scored ≥70%, stage Ⅱ/Ⅲ rectal cancer after curative surgery were eligible. Total RT dose was delivered as DT 50 Gy in the fraction of 2.0 Gy per day for 5 weeks to the pelvic area. 5-dFUR was administered concurrently with radiotherapy in escalating doses, and oral leucovorin was The DLTs included grade 3 or grade 4 hematologic and nonhematologic toxicity. Results From Aug. 2005 the most common side effects although all neutropenia was less grade 3. The DLT was observed in 1 patient of RT. In the following 3 enrolled patients, one suffered grade 3 abdominal cramp pain, diarrhea, fatigue, nausea/vomit and grade 2 neutropinea and fever. Grade 3 diarrhea was also observed in all the additional 3 papatients didn't complete the scheduled concurrent chemoradiotherapy due to severe side effects,including 1 at grade 3 abdominal cramp pain,fatigue and nausea/vomit. Conclusions Diarrhea is the most common and severe side effect in this phase Ⅰ study. The MTD of doxifluridine, concurrently with RT and fixed dose of oral cramp pain is often accompanied with diarrhea and nauser/vomit when the dose of doxifluridine exceeds 550 mg/( m2 · d) or 900 mg/d,patients need to be observed carefully.