A Phase II Trial Of Adjuvant Chemoradiation Following Pancreatic Resection For Adenocarcinomas Of The Pancreas Using 3-D Conformal Radiation With Cisplatin, 5FU, And Alpha-Interferon As Radiosensitizing Agents Followed By Gemcitabine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- To describe the overall survival and disease-free survival
研究概览
简要总结
To describe the overall survival and disease-free survival in pancreatic cancer patients treated with adjuvant chemoradiation with cisplatin, continuous infusion 5FU and interferon alpha followed by gemcitabine.
To describe the toxicities associated with adjuvant chemoradiation with cisplatin. 5FU and interferon alfa followed by gemcitabine in patients with pancreatic cancers.
详细描述
The adjuvant therapy of pancreas cancer has remained a challenge for oncology specialists from all disciplines since the initial development of the pancreaticoduodenectomy by Whipple in 1935 (Whipple, Ann Surg, 1935). A variety of phase II experiences utilizing radiation therapy and 5FU-based chemotherapy following curative surgery for pancreas cancer have consistently produced the disappointing survival results of 18-24 months median survival, 40%-50% 2-year survival and 10%-20% 5-year survival (Evans, in DeVita, et.al Cancer Principles and Practices of Oncology, 1997). Indeed, whether any adjuvant therapy following pancreaticoduodenectomy for pancreas cancer is of benefit to patients remains a debated question. The landmark study performed by the GITSG in patients with pancreatic cancer displayed a survival advantage for patients receiving postoperative radiation therapy and 5FU compared to those receiving pancreaticoduodenectomy only (2-year survival 43% vs. 18%, p=0.03). As a result, this study became to some the standard of care for patients with resected pancreas cancer in the US (GITSG, Cancer 1987). However, this study rightfully has been criticized from a variety of perspectives over the years; furthermore, recent experiences by the EROTC and ESPAC have failed to reproduce the GITSG results (Klinkenbijl, Ann Surg 1999,Neoptolemos, Proc ASCO 2000). However, the results of these two studies have also received significant criticisms. The EORTC data are underpowered and the study failed to use post-radiation chemotherapy to optimum advantage. The ESPAC data have been criticized as being statistically invalid by trial desig10/14/02n and analysis. Thus, the optimization of adjuvant therapy following pancreaticoduodenectomy for pancreas cancer remains a subject of debate and poses essentially the same challenge to oncology specialists at the beginning of the 21st century as it has for the past sixty years.
Confronted with these issues, investigators at the Virginia Mason Clinic began in 1995 a phase II trial utilizing cisplatin and alpha-interferon in conjunction with 5FU and radiation therapy following pancreaticoduodenectomy for pancreatic adenocarcinoma. The logic behind this protocol was as follows:
- Recurrence following surgery and adjuvant chemoradiation in protocols for resected pancreas cancer to that date had been associated with a high incidence of both local and systemic recurrence; thus treatment must focus on improvement in relapse rates in both areas.
- No chemotherapy regimens (as of 1995), either single agent or multi-agent, had shown response rates markedly different from that seen with single agent 5FU (typically on the order of 10%)
- Therapeutic advance in the adjuvant therapy of pancreas cancer must therefore focus on systemic agents that have the potential to synergize the tumoricidal activity of radiation therapy and/or each other.
- Cisplatin and alpha-interferon, like 5FU, do have radiosensitizing activity in experimental tumor systems and thus potentially could be added to 5FU to create a "combination" radiosensitizing agent analogous to the way chemotherapy agents are combined for systemic effect.
- These chemotherapeutic agents also have direct synergistic anticancer activity with respect to each other in experimental tumor systems .
- These agents also have, to a large extent, non-overlapping toxicities and can be delivered on an outpatient basis.
Using the above logic, a novel phase II protocol (with radiation therapy) for the adjuvant therapy of pancreas cancer was developed. The protocol was constructed as follows:
- XRT 5000cGy/200cGy fractions given daily M-F wks 1-5
- CDDP 30 mg/m2 d 1 wks 1-5
- IFN-A 3,000,000U sq qod wks 1-5 beginning d 1
- 5FU 200mg/m2 wks 1-5 beginning d 1; repeated wks 10-15 and wks 18-23 (2 6 wk chemotherapy courses post chemoradiation ).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1
Surgery (pancreaticoduodenectomy, either standard or pylorus-preserving, with either standard or extended lymph node dissection, with or without portal vein resection) should occur at 8 weeks (plus or minus 2, not to exceed 10)
Radiation therapy will occur 8 weeks (plus or minus 2, not to exceed 10) postoperatively. Daily dose of 1.8 Gy five days per week. The first 45 Gy will be given to planning target volume 1. After 45 Gy, portals will be reduced to encompass planning target volume 2. The boost dose will be 5.4 Gy.
Cisplatin IV 25 mg/m2 on days 1, 8, 15, 22, 29, and 36 during radiation.
5-FU CIVI at 175 mg/m2/d on days 1-38 without interruption during radiation.
Alpha-interferon SQ 3,000,000 units on Mondays, Wednesdays, and Fridays during radiation therapy.
Gemcitabine IV 1000 mg/m2 4 weeks after conclusion of radiation (on a 3 weeks on/1 week off schedule) on days 71, 78, 85, 99, 106, and 113.
干预措施: Pancreatic Surgery (Procedure)
Arm 1
Surgery (pancreaticoduodenectomy, either standard or pylorus-preserving, with either standard or extended lymph node dissection, with or without portal vein resection) should occur at 8 weeks (plus or minus 2, not to exceed 10)
Radiation therapy will occur 8 weeks (plus or minus 2, not to exceed 10) postoperatively. Daily dose of 1.8 Gy five days per week. The first 45 Gy will be given to planning target volume 1. After 45 Gy, portals will be reduced to encompass planning target volume 2. The boost dose will be 5.4 Gy.
Cisplatin IV 25 mg/m2 on days 1, 8, 15, 22, 29, and 36 during radiation.
5-FU CIVI at 175 mg/m2/d on days 1-38 without interruption during radiation.
Alpha-interferon SQ 3,000,000 units on Mondays, Wednesdays, and Fridays during radiation therapy.
Gemcitabine IV 1000 mg/m2 4 weeks after conclusion of radiation (on a 3 weeks on/1 week off schedule) on days 71, 78, 85, 99, 106, and 113.
干预措施: Radiation therapy (Radiation)
Arm 1
Surgery (pancreaticoduodenectomy, either standard or pylorus-preserving, with either standard or extended lymph node dissection, with or without portal vein resection) should occur at 8 weeks (plus or minus 2, not to exceed 10)
Radiation therapy will occur 8 weeks (plus or minus 2, not to exceed 10) postoperatively. Daily dose of 1.8 Gy five days per week. The first 45 Gy will be given to planning target volume 1. After 45 Gy, portals will be reduced to encompass planning target volume 2. The boost dose will be 5.4 Gy.
Cisplatin IV 25 mg/m2 on days 1, 8, 15, 22, 29, and 36 during radiation.
5-FU CIVI at 175 mg/m2/d on days 1-38 without interruption during radiation.
Alpha-interferon SQ 3,000,000 units on Mondays, Wednesdays, and Fridays during radiation therapy.
Gemcitabine IV 1000 mg/m2 4 weeks after conclusion of radiation (on a 3 weeks on/1 week off schedule) on days 71, 78, 85, 99, 106, and 113.
干预措施: Cisplatin (Drug)
Arm 1
Surgery (pancreaticoduodenectomy, either standard or pylorus-preserving, with either standard or extended lymph node dissection, with or without portal vein resection) should occur at 8 weeks (plus or minus 2, not to exceed 10)
Radiation therapy will occur 8 weeks (plus or minus 2, not to exceed 10) postoperatively. Daily dose of 1.8 Gy five days per week. The first 45 Gy will be given to planning target volume 1. After 45 Gy, portals will be reduced to encompass planning target volume 2. The boost dose will be 5.4 Gy.
Cisplatin IV 25 mg/m2 on days 1, 8, 15, 22, 29, and 36 during radiation.
5-FU CIVI at 175 mg/m2/d on days 1-38 without interruption during radiation.
Alpha-interferon SQ 3,000,000 units on Mondays, Wednesdays, and Fridays during radiation therapy.
Gemcitabine IV 1000 mg/m2 4 weeks after conclusion of radiation (on a 3 weeks on/1 week off schedule) on days 71, 78, 85, 99, 106, and 113.
干预措施: 5-FU (Drug)
Arm 1
Surgery (pancreaticoduodenectomy, either standard or pylorus-preserving, with either standard or extended lymph node dissection, with or without portal vein resection) should occur at 8 weeks (plus or minus 2, not to exceed 10)
Radiation therapy will occur 8 weeks (plus or minus 2, not to exceed 10) postoperatively. Daily dose of 1.8 Gy five days per week. The first 45 Gy will be given to planning target volume 1. After 45 Gy, portals will be reduced to encompass planning target volume 2. The boost dose will be 5.4 Gy.
Cisplatin IV 25 mg/m2 on days 1, 8, 15, 22, 29, and 36 during radiation.
5-FU CIVI at 175 mg/m2/d on days 1-38 without interruption during radiation.
Alpha-interferon SQ 3,000,000 units on Mondays, Wednesdays, and Fridays during radiation therapy.
Gemcitabine IV 1000 mg/m2 4 weeks after conclusion of radiation (on a 3 weeks on/1 week off schedule) on days 71, 78, 85, 99, 106, and 113.
干预措施: Alpha-interferon (Drug)
Arm 1
Surgery (pancreaticoduodenectomy, either standard or pylorus-preserving, with either standard or extended lymph node dissection, with or without portal vein resection) should occur at 8 weeks (plus or minus 2, not to exceed 10)
Radiation therapy will occur 8 weeks (plus or minus 2, not to exceed 10) postoperatively. Daily dose of 1.8 Gy five days per week. The first 45 Gy will be given to planning target volume 1. After 45 Gy, portals will be reduced to encompass planning target volume 2. The boost dose will be 5.4 Gy.
Cisplatin IV 25 mg/m2 on days 1, 8, 15, 22, 29, and 36 during radiation.
5-FU CIVI at 175 mg/m2/d on days 1-38 without interruption during radiation.
Alpha-interferon SQ 3,000,000 units on Mondays, Wednesdays, and Fridays during radiation therapy.
Gemcitabine IV 1000 mg/m2 4 weeks after conclusion of radiation (on a 3 weeks on/1 week off schedule) on days 71, 78, 85, 99, 106, and 113.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
To describe the overall survival and disease-free survival
时间窗: 2 years
次要结局
- To describe the toxicities associated with adjuvant chemoradiation with cisplatin, 5FU and interferon alfa followed by gemcitabine in patients with pancreatic cancers.(Week 15)