Evaluation of the Efficacy and Toxicity of Neo-adjuvant Short Course Radiation Therapy Concurrently With Continuous Infusion 5-fluorouracil in the Management of Locally Advanced Rectal Cancer Patients
试验速览
- 阶段
- 2 期
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Incidence of treatment adverse events as assessed by National Cancer Institute Common Terminology Criteria for adverse events version 4.0
研究概览
简要总结
- The primary objective of this trial is to assess the safety and feasibility of 5-FU when given concurrently with5 Gy x 5 fractions IMRT.
- The secondary endpoint is to assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery.
详细描述
Neo-adjuvant radiotherapy is associated with the improvement of local control for rectal cancer. For locally advanced stage II-III resectable rectal cancer, either preoperative short-course radiotherapy of 25 Gy in 5 consecutive days or long-course chemo-radiotherapy followed by radical Total Meso-rectal Excision is recommended. The Swedish Rectal Cancer Trial has demonstrated the lower rate of early toxicity of short course radiotherapy when compared to chemo-radiation. Short-course irradiation reduced the risk of local recurrence with evidence of overall survival improvement. Short-course regimen is less expensive and more convenient, especially in centers with long waiting lists. Two meta-analyses showed that short course is as effective as long course chemo-radiation in the management of locally advanced rectal cancer in the terms of sphincter preservation rates, down-staging, R0 resection, local control, and grade 3-4 toxicity. Despite reduction in local-regional recurrence risk with neo-adjuvant short course radiotherapy, distant disease recurrence remains a substantial risk for patients with locally advanced disease. In a controlled randomized trial, a short course radiotherapy followed by consolidation chemotherapy prior to surgery yielded superior overall survival outcomes compared to chemo-radiotherapy, without significant differences in disease-free survival, nor local or distant disease control rates. The phase III RAPIDO and STELLAR clinical trials are also evaluating short course radiotherapy and consolidation chemotherapy. The Stockholm III trial was a 3-arm trial that compared short-course RT with the standard 1-week delay to surgery, short-course RT with a 4- to 6-week delay to surgery, and long-course chemoradiation with a 4- to 6-week delay to surgery. The results show similar outcomes between the groups, but delaying the surgery after short-course RT decreased the rates of high-grade toxicity and allowed for an expedited treatment program.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathological confirmed cancer rectum
- •Age between 20-80
- •Clinical T3\4 or node positive disease by MRI
排除标准
- •Early stage cancer rectum
- •M1 disease confirmed by imaging or pathological
研究组 & 干预措施
neoadjuvant chemo-radiation
Short-course RT: 5 fractions of 5 Gy to a total dose of 25 Gy over 5 consecutive days. IMRT plans are generated with 6 MV photons.
Dose-escalated concurrent 5-FU: The 3 doses levels of 5-FU are 100, 150, and 200 mg/m2/d. 5-FU will be given by continuous infusion for 20 hours every day starting on the morning of radiation.
mFOLFOX: will be given 2 weeks after concurrent chemoradiation for a total of 4 cycles, with each cycle being 14 days. Surgery will be omitted in patients with complete pathological response and proceed to adjuvant chemotherapy. If patient develops progressive or metastatic disease, he/she will be omitted from the investigators study.
The surgery will be considered 4-8 weeks after end of therapy. Adjuvant mFOLFOX6: 6 cycles chemotherapy will begin between 4 weeks and 8 weeks after surgery.
Toxicities assessment: be using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
干预措施: short course chemo-radiation with 5-fluorouracil (Drug)
结局指标
主要结局
Incidence of treatment adverse events as assessed by National Cancer Institute Common Terminology Criteria for adverse events version 4.0
时间窗: baseline
Dose limiting toxicity is defined as any of the following occurring during chemo radiation or within 21 days from the completion of the treatment like grade 4 non hematological toxicity, grade 4 febrile neutropenia, grade 4 thrombocytopenia or neutropenia toxicity lasting 7 days, grade 3 non hematological toxicity preventing treatment more than 3 days, elevation of ALT or AST more than 10 the upper limit of normal for 7 days
次要结局
- assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery.(2 years)
研究者
Mariam Mohsen Khalil
principal investigator
Assiut University