Concurrent Radiotherapy and Weekly Chemotherapy of PF for Postoperative Locoregional Recurrence of Esophageal Cancer

Concurrent Radiotherapy and Weekly Chemotherapy of 5-fluorouracil and Cisplatin for Postoperative Locoregional Recurrence of Oesophageal Squamous Cell Carcinoma

The purpose of this study is to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly chemotherapy of 5-FU and cisplatin in patients with postoperative locoregional recurrence of esophageal squamous cell carcinoma.

Study Overview

• Status: Unknown
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: fluorouracil; Drug: Cisplatin; Radiation: Intensity-modulated radiation therapy

Detailed Description

The most optimal management for postoperative locoregional recurrence of oesophageal squamous cell carcinoma is still controversial. Several studies have reported the feasibility and efficacy of concurrent chemoradiotherapy (CCRT), mostly with three-weekly or four-weekly schedule of chemotherapy. However, treatment compliance was not quite satisfactory, probably due to treatment-related toxicities. Since CCRT with weekly chemotherapy regimens have demonstrated a favorable toxicity profile as well as promising survival in certain types of cancer, the investigators aimed to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly chemotherapy with 5-fluorouracil (5-FU) and cisplatin for patients with postoperative locoregional recurrence of oesophageal squamous cell carcinoma in the investigators center.The prescribed dose of radiotherapy is generally 60Gy/28fr to tumor and 50Gy/28fr to the clinical target volume.The concomitant chemotherapy is cisplatin 25mg/m2 on day 1, 5-FU 1176mg/m2 on day 1-3, repeated weekly for 4 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yujia Zhu, MD; Phone Number: 86-20-87343385; Email: zhuyuj@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • SYSU Cancer Center
      • Contact: Yujia Zhu, Phd.; Phone Number: 18520121368; Email: sysucc@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. R0 resection for primary esophageal squamous cell carcinoma with two-incision esophagectomy (Ivor Lewis approach)25 or three-incision (right thoracotomy, midline laparotomy and left cervical incisions) esophagectomy with cervical esophagogastric anastomosis.
2. Absence of previous thoracic radiotherapy.
3. Cervical and/or thoracic postoperative recurrence (biopsy proven or positron emission tomography/computed tomography (PET/CT) proven or follow-up computed tomography (CT) showed progression of disease).
4. Absence of distant metastasis at recurrence.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2

Exclusion Criteria:

1. Younger than 18 or older than 70 years of age.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 3 or above
3. Other cancer history.
4. Serious cardiac, liver, or pulmonary disease.
5. Previous radiotherapy history

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Weekly PF with radiation; 4 cycles of weekly cisplatin and fluorouracil (cisplatin 25mg/m2 on day 1, fluorouracil 1176mg/m2 on day 1-3, repeated weekly for 4 weeks) concurrently with Intensity-modulated radiation therapy (60Gy/28fr).

Drug: fluorouracil; cisplatin 25mg/m2 on day 1, fluorouracil 1176mg/m2 on day 1-3，repeated weekly for 4 weeks concurrently with IMRT radiotherapy (60Gy/28fr); Other Names: 5-FU; Drug: Cisplatin; cisplatin 25mg/m2 on day 1, fluorouracil 1176mg/m2 on day 1-3，repeated weekly for 4 weeks concurrently with IMRT radiotherapy (60Gy/28fr); Radiation: Intensity-modulated radiation therapy; cisplatin 25mg/m2 on day 1, fluorouracil 1176mg/m2 on day 1-3，repeated weekly for 4 weeks concurrently with IMRT radiotherapy (60Gy/28fr); Other Names: IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate	RECIST (Response Evaluation Criteria in Solid Tumors) was used to determine the tumor response. Tumor response was evaluated by CT 8 weeks after chemoradiotherapy.	within 8 weeks after the treatment(plus or minus 5 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety: Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0).	A 3 years follow-up from the enrollment or to the date of death from any cause or date of lost follow-up	up to 3 years
overall survival	A 3 years follow-up from the enrollment or to the date of death from any cause or date of lost follow-up	up to 3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Yujia Zhu, MD, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China

Publications and helpful links

General Publications

• Rice TW, Rusch VW, Apperson-Hansen C, Allen MS, Chen LQ, Hunter JG, Kesler KA, Law S, Lerut TE, Reed CE, Salo JA, Scott WJ, Swisher SG, Watson TJ, Blackstone EH. Worldwide esophageal cancer collaboration. Dis Esophagus. 2009;22(1):1-8. doi: 10.1111/j.1442-2050.2008.00901.x.
• Kato H, Miyazaki T, Nakajima M, Sohda M, Fukai Y, Masuda N, Fukuchi M, Manda R, Tsukada K, Kuwano H. Prediction of hematogenous recurrence in patients with esophageal carcinoma. Jpn J Thorac Cardiovasc Surg. 2003 Nov;51(11):599-608. doi: 10.1007/BF02736700.
• Nakamura T, Ota M, Narumiya K, Sato T, Ohki T, Yamamoto M, Mitsuhashi N. Multimodal treatment for lymph node recurrence of esophageal carcinoma after curative resection. Ann Surg Oncol. 2008 Sep;15(9):2451-7. doi: 10.1245/s10434-008-0016-x. Epub 2008 Jul 1.
• Shioyama Y, Nakamura K, Ohga S, Nomoto S, Sasaki T, Yamaguchi T, Toba T, Yoshitake T, Terashima H, Honda H. Radiation therapy for recurrent esophageal cancer after surgery: clinical results and prognostic factors. Jpn J Clin Oncol. 2007 Dec;37(12):918-23. doi: 10.1093/jjco/hym138.
• Kobayashi R, Yamashita H, Okuma K, Shiraishi K, Ohtomo K, Nakagawa K. Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer. Dis Esophagus. 2014 Jan;27(1):72-8. doi: 10.1111/dote.12068. Epub 2013 Apr 2.
• Yuan G, Wu L, Huang M, Li N, An J. A phase II study of concurrent chemo-radiotherapy with weekly nedaplatin in advanced squamous cell carcinoma of the uterine cervix. Radiat Oncol. 2014 Feb 18;9:55. doi: 10.1186/1748-717X-9-55.
• Nakagawa S, Kanda T, Kosugi S, Ohashi M, Suzuki T, Hatakeyama K. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. J Am Coll Surg. 2004 Feb;198(2):205-11. doi: 10.1016/j.jamcollsurg.2003.10.005.
• Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, Klump B, Budach W, Teichmann R, Schmitt M, Schmitt G, Franke C, Wilke H. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005 Apr 1;23(10):2310-7. doi: 10.1200/JCO.2005.00.034. Erratum In: J Clin Oncol. 2006 Jan 20;24(3):531.
• Bao Y, Liu S, Zhou Q, Cai P, Anfossi S, Li Q, Hu Y, Liu M, Fu J, Rong T, Li Q, Liu H. Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern. Radiat Oncol. 2013 Oct 18;8:241. doi: 10.1186/1748-717X-8-241.
• Jingu K, Nemoto K, Matsushita H, Takahashi C, Ogawa Y, Sugawara T, Nakata E, Takai Y, Yamada S. Results of radiation therapy combined with nedaplatin (cis-diammine-glycoplatinum) and 5-fluorouracil for postoperative locoregional recurrent esophageal cancer. BMC Cancer. 2006 Mar 4;6:50. doi: 10.1186/1471-2407-6-50.
• Ma DY, Tan BX, Liu M, Li XF, Zhou YQ, Lu Y. Concurrent three-dimensional conformal radiotherapy and chemotherapy for postoperative recurrence of mediastinal lymph node metastases in patients with esophageal squamous cell carcinoma: a phase 2 single-institution study. Radiat Oncol. 2014 Jan 19;9:28. doi: 10.1186/1748-717X-9-28.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: December 16, 2014
• First Submitted That Met QC Criteria: December 19, 2014
• First Posted (Estimate): December 25, 2014

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 19, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: chemotherapy; radiotherapy; esophageal carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Recurrence; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cisplatin; Fluorouracil
• Other Study ID Numbers: GD-B2014157