S0356 Oxaliplatin, 5-FU, Radiation Therapy (RT), Surgery for Pts With Stage II or III Cancer of Esophagus or Gastroesophageal (GE) Junction

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00086996
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 98
• Locations: 143
• Arm: 1
• Duration (Months): 83
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Oxaliplatin and fluorouracil may make tumor cells more sensitive to radiation therapy and may kill more tumor cells. Giving chemotherapy and radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving oxaliplatin together with fluorouracil and radiation therapy works in treating patients who are undergoing surgery for stage II or stage III cancer of the esophagus or gastroesophageal junction.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: fluorouracil; Drug: oxaliplatin; Procedure: conventional surgery; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the pathologic complete response probability in patients with stage II or III adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant oxaliplatin, fluorouracil, and radiotherapy followed by definitive surgical resection.

Secondary

• Determine the frequency and severity of toxic effects associated with this neoadjuvant regimen in these patients.

• Determine the overall survival and progression-free survival of patients treated with this regimen.

Exploratory Analyses (subject to funding availability)

• Correlate, preliminarily, initial messenger ribonucleic acid (mRNA) levels of the genes for thymidylate synthase (TS), γ-glutamyl transpeptidase (γGT), γ-glutamyl cysteine (γ-GCS), DNA excision repair cross-complementing (ERCC-1), and xeroderma pigmentosum (XPA) with response and survival of patients treated with this regimen.

• Correlate, preliminarily, the mRNA levels of TS, γGT, γ-GCS, ERCC-1, and XPA before and after treatment with this regimen with survival of these patients.

• Correlate, preliminarily, specific genetic polymorphisms of TS and ERCC-1 with tumor response and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil (5-FU) IV continuously on days 8-43. Beginning on day 8, patients also undergo radiotherapy once daily, 5 days a week, for 5 weeks.

• Surgery: Patients with stable disease or better undergo surgical resection 4-10 weeks after completion of chemoradiotherapy.

• Adjuvant chemotherapy: Beginning 4-10 weeks after surgery, patients receive chemotherapy comprising oxaliplatin IV over 2 hours on days 1, 15, and 29 and 5-FU IV continuously on days 1-36.

Treatment continues in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 45-85 patients will be accrued for this study within 17-21 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Chemo Plus RT, Surgery, Chemo neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin

Drug: fluorouracil; Before surgery: 180 mg/m2/day by 24-hour infusion days 8 through 43. After surgery:180 mg/m2/day by 24-hour infusion days 1 through 36.; Other Names: 5-FU ; Drug: oxaliplatin; Before surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29. After surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29.; Other Names: eloxatin ; Procedure: conventional surgery; The surgical technique will depend upon the location and extent of tumor and individual surgeon preference.; Radiation: radiation therapy; Starting Day 8, patients will be treated 5 days/week at 180 centigray (cGy)/day times 25 fractions to a total dose of 4,500 cGy.

Outcome Measures

Primary Outcome Measures

1. Pathological Complete Response [10-16 weeks after beginning study treatment]

   Complete pathologic response assessed after chemoradiotherapy and surgery, defined as no evidence of residual disease on path review. Patients who did not receive surgery are assumed to have not responded.

Secondary Outcome Measures

1. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [Up to 3 years]

   Only adverse events that are possibly, probably or definitely related to study drug are reported.

2. Overall Survival [0-5 years]

   Measured from time of registration to death, or last contact date

3. Progression-free Survival [0-3 years]

   measured from date of registration to time of first documentation of progression by Response Evaluation Criteria in Solid Tumors (RECIST), death, or last contact date.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed primary adenocarcinoma of the thoracic esophagus or gastroesophageal junction

• No recurrent disease

• Primary esophageal tumor at least 20 cm below the incisors (if < 26 cm below the incisors, a bronchoscopy must be performed and cytology must be negative)

• Esophageal disease confined to esophagus and peri-esophageal soft tissue

• Gastroesophageal junction disease extending ≤ 2 cm into the gastric cardia

• Clinical stage II or III disease by CT scan or MRI

• If no esophageal mass is detected by these methods, esophageal endoscopic ultrasound is required to determine stage

• Positron-emission tomography scan is required to confirm stage

• Measurable or non-measurable disease by x-ray, scanning, or physical examination

• No celiac axis nodes ≥ 1.5 cm

• Measurable regional lymph nodes ≥ 1.5 cm at stations 2-10=N1 OR subdiaphragmatic lymph nodes at stations 15-19 ≤ 1.5 cm by CT scan or MRI allowed

• Palpable supraclavicular lymph nodes must be free of metastatic esophageal cancer by biopsy

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3

• White blood cell (WBC) count ≥ 3,000/mm^3

• Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

• Albumin ≥ 3 g/dL

• Bilirubin normal

Renal

• Creatinine ≤ 1.5 times upper limit of normal

Cardiovascular

• No myocardial infarction or cerebrovascular event within the past 6 months

Pulmonary

• No active pneumonia or inflammatory lung infiltrate

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

• No peripheral neuropathy ≥ grade 2

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for esophageal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for esophageal cancer

• No concurrent intensity-modulated radiotherapy

Surgery

• No prior surgical resection or attempted surgical resection of esophageal cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36652-2144
2	Providence Cancer Center	Anchorage	Alaska	United States	99508
3	Highlands Oncology Group - Springdale	Bentonville	Arkansas	United States	72712
4	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
5	Eden Medical Center	Castro Valley	California	United States	94546
6	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California	United States	94546
7	Valley Medical Oncology	Fremont	California	United States	94538
8	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
9	Highland General Hospital	Oakland	California	United States	94602
10	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
11	Bay Area Breast Surgeons, Incorporated	Oakland	California	United States	94609
12	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
13	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
14	Tom K Lee, Incorporated	Oakland	California	United States	94609
15	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California	United States	92262
16	Valley Care Medical Center	Pleasanton	California	United States	94588
17	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California	United States	94588
18	University of California Davis Cancer Center	Sacramento	California	United States	95817
19	Doctors Medical Center - San Pablo Campus	San Pablo	California	United States	94806
20	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
21	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
22	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
23	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
24	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
25	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
26	Good Samaritan Regional Health Center	Mt. Vernon	Illinois	United States	62864
27	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
28	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
29	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
30	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
31	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
32	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
33	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
34	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
35	Southwest Medical Center	Liberal	Kansas	United States	67901
36	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
37	Olathe Cancer Center	Olathe	Kansas	United States	66061
38	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
39	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
40	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
41	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
42	St. Francis Comprehensive Cancer Center	Topeka	Kansas	United States	66606
43	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
44	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
45	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
46	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
47	CCOP - Wichita	Wichita	Kansas	United States	67214
48	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
49	Wesley Medical Center	Wichita	Kansas	United States	67214
50	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
51	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
52	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118
53	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
54	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
55	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
56	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
57	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
58	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
59	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
60	Metro Health Hospital	Grand Rapids	Michigan	United States	49506
61	Holland Community Hospital	Holland	Michigan	United States	49423
62	Hackley Hospital	Muskegon	Michigan	United States	49442
63	Munson Medical Center	Traverse City	Michigan	United States	49684
64	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
65	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri	United States	63701
66	St. John's Regional Medical Center	Joplin	Missouri	United States	64804
67	CCOP - Kansas City	Kansas City	Missouri	United States	64131
68	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
69	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
70	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
71	St. John's Regional Health Center	Springfield	Missouri	United States	65804
72	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
73	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
74	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
75	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
76	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
77	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
78	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
79	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
80	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
81	Frontier Cancer Center	Great Falls	Montana	United States	59405
82	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
83	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
84	St. Peter's Hospital	Helena	Montana	United States	59601
85	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
86	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
87	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
88	Community Medical Center	Missoula	Montana	United States	59801
89	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
90	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
91	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
92	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
93	Tucker Center for Cancer Care at Orange Regional Medical Center	Middletown	New York	United States	10940-4199
94	Randolph Hospital	Asheboro	North Carolina	United States	27203-5400
95	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
96	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina	United States	27403-1198
97	Annie Penn Cancer Center	Reidsville	North Carolina	United States	27320
98	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
99	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
100	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
101	Grandview Hospital	Dayton	Ohio	United States	45405
102	Good Samaritan Hospital	Dayton	Ohio	United States	45406
103	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
104	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
105	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
106	CCOP - Dayton	Dayton	Ohio	United States	45429
107	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
108	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
109	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
110	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
111	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
112	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
113	AnMed Cancer Center	Anderson	South Carolina	United States	29621
114	CCOP - Greenville	Greenville	South Carolina	United States	29615
115	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
116	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
117	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
118	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
119	American Fork Hospital	American Fork	Utah	United States	84003
120	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
121	Logan Regional Hospital	Logan	Utah	United States	84321
122	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
123	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
124	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
125	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
126	LDS Hospital	Salt Lake City	Utah	United States	84103
127	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
128	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia	United States	24273
129	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
130	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
131	Columbia Basin Hematology	Kennewick	Washington	United States	99336
132	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
133	Harborview Medical Center	Seattle	Washington	United States	98104
134	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
135	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
136	Group Health Central Hospital	Seattle	Washington	United States	98112
137	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
138	Polyclinic First Hill	Seattle	Washington	United States	98122
139	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
140	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
141	Rockwood Clinic Cancer Treatment Center	Spokane	Washington	United States	99204-2967
142	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
143	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Lawrence P. Leichman, MD, Desert Regional Medical Center Comprehensive Cancer Center
• Study Chair: Charles R. Thomas, MD, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00086996
• Other Study ID Numbers: CDR0000371963; U10CA032102; S0356
• First Posted: Jul 12, 2004
• Last Update Posted: Oct 11, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Southwest Oncology Group: adenocarcinoma of the esophagus; stage II esophageal cancer; stage III esophageal cancer
• Additional relevant MeSH terms: Esophageal Neoplasms; Fluorouracil; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	Chemo Plus RT, Surgery, Chemo
Arm/Group Description	Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin 85 mg/m^2 by 2-hour IV infusion days 1, 15, and 29 and fluorouracil (5-FU) 180 mg/m^2/day infusion continuously on days 8-43. Beginning on day 8, patients also undergo radiotherapy at 180 centigray (cGy)/day, 5 days a week, for 5 weeks to a total dose of 4,500 cGy. Surgery: Patients with stable disease or better undergo surgical resection 4-10 weeks after completion of chemoradiotherapy. The surgical technique will depend upon the location and extent of tumor and individual surgeon preference. Adjuvant chemotherapy: Beginning 4-10 weeks after surgery, patients receive chemotherapy comprising oxaliplatin 85 mg/m^2 by 2-hour IV infusion days 1, 15, and 29 and 5-FU 180 mg/m^2/day by 24-hour infusion continuously on days 1-36.
Period Title: Overall Study
STARTED	98
Eligible	93
Eligible and Began Protocol Therapy	93
COMPLETED	34
NOT COMPLETED	64

Baseline Characteristics

Arm/Group Title	Chemo Plus RT, Surgery, Chemo
Arm/Group Description	Neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin
Overall Participants	93
Age (participants) [Median (Full Range) ]
Median (Full Range) [participants]	62.2 66.9%
Sex: Female, Male (Count of Participants)
Female	6 6.5%
Male	87 93.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2.2%
Not Hispanic or Latino	86 92.5%
Unknown or Not Reported	5 5.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2.2%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.2%
White	86 92.5%
More than one race	0 0%
Unknown or Not Reported	3 3.2%

Outcome Measures

1. Primary Outcome

Title	Pathological Complete Response
Description	Complete pathologic response assessed after chemoradiotherapy and surgery, defined as no evidence of residual disease on path review. Patients who did not receive surgery are assumed to have not responded.
Time Frame	10-16 weeks after beginning study treatment

Outcome Measure Data

Analysis Population Description

Eligible patients

Arm/Group Title	Chemo Plus RT, Surgery, Chemo
Arm/Group Description	Neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin
Measure Participants	93
Number [participants]	26 28%

2. Secondary Outcome

Title	Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Description	Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any Common Terminology Criteria for Adverse Events (CTCAE) v3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Arm/Group Title	Chemo Plus RT, Surgery, Chemo
Arm/Group Description	Neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin
Measure Participants	93
Adult respiratory distress syndrome (ARDS)	4 4.3%
Anorexia	15 16.1%
CNS cerebrovascular ischemia	1 1.1%
Calcium, serum-low (hypocalcemia)	2 2.2%
Cardiac troponin T (cTnT)	1 1.1%
Cardiac-ischemia/infarction	1 1.1%
Chyle or lymph leakage	1 1.1%
Confusion	1 1.1%
Cough	1 1.1%
Creatinine	1 1.1%
Dehydration	3 3.2%
Diarrhea	12 12.9%
Distention/bloating, abdominal	1 1.1%
Dysphagia (difficulty swallowing)	4 4.3%
Dyspnea (shortness of breath)	3 3.2%
Esophagitis	3 3.2%
Fatigue (asthenia, lethargy, malaise)	14 15.1%
Febrile neutropenia	1 1.1%
Fever in absence of neutropenia, ANC lt1.0x10e9/L	1 1.1%
Fistula, GI - Oral cavity	1 1.1%
Gastrointestinal-Other (Specify)	1 1.1%
Glucose, serum-high (hyperglycemia)	3 3.2%
Heartburn/dyspepsia	1 1.1%
Hemoglobin	4 4.3%
Hypotension	1 1.1%
Hypoxia	6 6.5%
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	1 1.1%
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	2 2.2%
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	3 3.2%
Inf w/normal ANC or Gr 1-2 neutrophils - Perit cav	1 1.1%
Inf w/normal ANC or Gr 1-2 neutrophils - Wound	4 4.3%
Infection with unknown ANC - Blood	1 1.1%
Infection with unknown ANC - Lung (pneumonia)	2 2.2%
Infection with unknown ANC - Wound	1 1.1%
Leak (including anastomotic), GI - Esophagus	1 1.1%
Leukocytes (total WBC)	2 2.2%
Lymphopenia	10 10.8%
Mood alteration - anxiety	1 1.1%
Mucositis/stomatitis (clinical exam) - Esophagus	1 1.1%
Mucositis/stomatitis (clinical exam) - Oral cavity	4 4.3%
Mucositis/stomatitis (functional/symp) - Esophagus	5 5.4%
Mucositis/stomatitis (functional/symp) - Oral cav	2 2.2%
Muscle weakness, not d/t neuropathy - body/general	1 1.1%
Nausea	11 11.8%
Necrosis, GI - Stomach	1 1.1%
Neutrophils/granulocytes (ANC/AGC)	1 1.1%
Obstruction, GI - Esophagus	1 1.1%
Pain - Abdomen NOS	1 1.1%
Pain - Pain NOS	1 1.1%
Pericardial effusion (non-malignant)	4 4.3%
Platelets	2 2.2%
Pleural effusion (non-malignant)	3 3.2%
Pneumonitis/pulmonary infiltrates	3 3.2%
Potassium, serum-low (hypokalemia)	4 4.3%
Pulmonary/Upper Respiratory-Other (Specify)	3 3.2%
Renal failure	1 1.1%
SVT and nodal arrhythmia - Atrial fibrillation	2 2.2%
SVT and nodal arrhythmia - Sinus tachycardia	1 1.1%
Skin breakdown/decubitus ulcer	1 1.1%
Sodium, serum-low (hyponatremia)	5 5.4%
Stricture/stenosis (incl anastomotic), Esophagus	2 2.2%
Syncope (fainting)	1 1.1%
Thrombosis/thrombus/embolism	2 2.2%
Typhlitis (cecal inflammation)	1 1.1%
Vomiting	7 7.5%
Weight loss	13 14%
Wound complication, non-infectious	1 1.1%

3. Secondary Outcome

Title	Overall Survival
Description	Measured from time of registration to death, or last contact date
Time Frame	0-5 years

Outcome Measure Data

Analysis Population Description

eligible patients

Arm/Group Title	Chemo Plus RT, Surgery, Chemo
Arm/Group Description	Neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin
Measure Participants	93
Median (95% Confidence Interval) [months]	28.3

4. Secondary Outcome

Title	Progression-free Survival
Description	measured from date of registration to time of first documentation of progression by Response Evaluation Criteria in Solid Tumors (RECIST), death, or last contact date.
Time Frame	0-3 years

Outcome Measure Data

Analysis Population Description

eligible patients

Arm/Group Title	Chemo Plus RT, Surgery, Chemo
Arm/Group Description	Neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin
Measure Participants	93
Median (95% Confidence Interval) [months]	19.7

Adverse Events

Time Frame	Up to 3 years
Arm/Group Title	Chemo Plus RT, Surgery, Chemo
Arm/Group Description	Neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin
All Cause Mortality
	Chemo Plus RT, Surgery, Chemo
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Chemo Plus RT, Surgery, Chemo
	Affected / at Risk (%)	# Events
Total	7/93 (7.5%)
Cardiac disorders
Cardiac-ischemia/infarction	1/93 (1.1%)
Pericardial effusion (non-malignant)	1/93 (1.1%)
SVT and nodal arrhythmia - Atrial fibrillation	1/93 (1.1%)
Gastrointestinal disorders
Typhlitis (cecal inflammation)	1/93 (1.1%)
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	1/93 (1.1%)
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	1/93 (1.1%)
Investigations
Cardiac troponin I (cTnI)	1/93 (1.1%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (ARDS)	2/93 (2.2%)
Hypoxia	2/93 (2.2%)
Vascular disorders
Thrombosis/thrombus/embolism	1/93 (1.1%)
Other (Not Including Serious) Adverse Events
	Chemo Plus RT, Surgery, Chemo
	Affected / at Risk (%)	# Events
Total	93/93 (100%)
Blood and lymphatic system disorders
Hemoglobin	67/93 (72%)
Cardiac disorders
SVT and nodal arrhythmia - Atrial fibrillation	16/93 (17.2%)
SVT and nodal arrhythmia - Sinus tachycardia	8/93 (8.6%)
Gastrointestinal disorders
Constipation	28/93 (30.1%)
Diarrhea	59/93 (63.4%)
Distention/bloating, abdominal	5/93 (5.4%)
Dysphagia (difficulty swallowing)	40/93 (43%)
Esophagitis	10/93 (10.8%)
Gastritis (including bile reflux gastritis)	5/93 (5.4%)
Gastrointestinal-Other (Specify)	8/93 (8.6%)
Heartburn/dyspepsia	18/93 (19.4%)
Mucositis/stomatitis (clinical exam) - Esophagus	5/93 (5.4%)
Mucositis/stomatitis (clinical exam) - Oral cavity	18/93 (19.4%)
Mucositis/stomatitis (functional/symp) - Esophagus	16/93 (17.2%)
Mucositis/stomatitis (functional/symp) - Oral cav	13/93 (14%)
Nausea	76/93 (81.7%)
Pain - Abdomen NOS	13/93 (14%)
Pain - Esophagus	17/93 (18.3%)
Stricture/stenosis (incl anastomotic), Esophagus	7/93 (7.5%)
Vomiting	42/93 (45.2%)
General disorders
Fatigue (asthenia, lethargy, malaise)	77/93 (82.8%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	19/93 (20.4%)
Pain - Chest/thorax NOS	9/93 (9.7%)
Pain-Other (Specify)	7/93 (7.5%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	5/93 (5.4%)
Inf w/normal ANC or Gr 1-2 neutrophils - Wound	8/93 (8.6%)
Injury, poisoning and procedural complications
Leak (including anastomotic), GI - Esophagus	5/93 (5.4%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	17/93 (18.3%)
AST, SGOT	16/93 (17.2%)
Alkaline phosphatase	23/93 (24.7%)
Bilirubin (hyperbilirubinemia)	11/93 (11.8%)
Creatinine	11/93 (11.8%)
Leukocytes (total WBC)	37/93 (39.8%)
Lymphopenia	15/93 (16.1%)
Metabolic/Laboratory-Other (Specify)	6/93 (6.5%)
Neutrophils/granulocytes (ANC/AGC)	12/93 (12.9%)
Platelets	43/93 (46.2%)
Weight loss	53/93 (57%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	31/93 (33.3%)
Anorexia	56/93 (60.2%)
Calcium, serum-low (hypocalcemia)	29/93 (31.2%)
Dehydration	25/93 (26.9%)
Glucose, serum-high (hyperglycemia)	36/93 (38.7%)
Glucose, serum-low (hypoglycemia)	6/93 (6.5%)
Magnesium, serum-low (hypomagnesemia)	5/93 (5.4%)
Potassium, serum-low (hypokalemia)	23/93 (24.7%)
Sodium, serum-low (hyponatremia)	29/93 (31.2%)
Musculoskeletal and connective tissue disorders
Pain - Back	5/93 (5.4%)
Pain - Muscle	6/93 (6.5%)
Nervous system disorders
Dizziness	13/93 (14%)
Neuropathy: sensory	55/93 (59.1%)
Pain - Head/headache	5/93 (5.4%)
Taste alteration (dysgeusia)	14/93 (15.1%)
Psychiatric disorders
Insomnia	10/93 (10.8%)
Mood alteration - anxiety	11/93 (11.8%)
Mood alteration - depression	13/93 (14%)
Renal and urinary disorders
Urinary retention (including neurogenic bladder)	5/93 (5.4%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	10/93 (10.8%)
Cough	19/93 (20.4%)
Dyspnea (shortness of breath)	13/93 (14%)
Hypoxia	11/93 (11.8%)
Pleural effusion (non-malignant)	13/93 (14%)
Pneumonitis/pulmonary infiltrates	8/93 (8.6%)
Pneumothorax	8/93 (8.6%)
Pulmonary/Upper Respiratory-Other (Specify)	5/93 (5.4%)
Skin and subcutaneous tissue disorders
Rash/desquamation	9/93 (9.7%)
Vascular disorders
Hypotension	9/93 (9.7%)
Thrombosis/thrombus/embolism	5/93 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.