Radiation Therapy and Chemotherapy Before and After Surgery in Treating Patients With Esophageal Cancer

Sponsor
Eastern Cooperative Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00033657
Collaborator
National Cancer Institute (NCI) (NIH)
97
23
2
89
4.2
0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy before and after surgery may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining radiation therapy with two different chemotherapy regimens before and after surgery in treating patients who have esophageal cancer.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OBJECTIVES:
  • Compare the pathologic complete response rate in patients with adenocarcinoma of the esophagus or gastroesophageal junction treated with radiotherapy with pre- and post-operative cisplatin plus paclitaxel versus cisplatin plus irinotecan.

  • Compare the survival outcome in patients treated with these regimens.

  • Compare the toxicity of these regimens in these patients.

  • Compare the tolerability of these adjuvant chemotherapy regimens after neoadjuvant chemoradiotherapy in these patients.

  • Compare time to progression or recurrence in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs. 1) and stage of disease (T2-3, N0, M0 vs. T1-3, N0-1, M0 or M1A). Patients are randomized to 1 of 2 treatment arms.

  • Arm A: Patients receive neoadjuvant radiotherapy once daily, 5 days a week, for 5 weeks beginning on day 1 concurrently with neoadjuvant chemotherapy comprising cisplatin IV (Intravenous) over 2-3 hours followed by irinotecan IV over 30-60 minutes once daily on days 1, 8, 22, and 29. Four to six weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection. A minimum of 4 weeks after resection, patients receive adjuvant chemotherapy comprising cisplatin and irinotecan as above on days 1 and 8. Treatment with adjuvant chemotherapy repeats every 3 weeks for 3 courses.

  • Arm B: Patients receive neoadjuvant radiotherapy as in arm A concurrently with neoadjuvant chemotherapy comprising paclitaxel IV (Intravenous) over 1 hour followed by cisplatin IV over 2-3 hours once daily on days 1, 8, 15, 22, and 29. Patients then undergo surgical resection as in arm A. A minimum of 4 weeks after resection, patients receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours followed by cisplatin as above on day 1. Treatment with adjuvant chemotherapy repeats every 3 weeks for 3 courses.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month, every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

ACCRUAL: A total of 97 patients (50 on Arm A and 47 on Arm B) were accrued for this study.

Study Design

Study Type:
Interventional
Actual Enrollment :
97 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Phase II Study of Preoperative Combined Modality Paclitaxel / Cisplatin / RT or Irinotecan / Cisplatin / RT Followed by Postoperative Chemotherapy With the Same Agents in Operable Adenocarcinoma of the Esophagus
Study Start Date :
May 1, 2002
Actual Primary Completion Date :
Sep 1, 2009
Actual Study Completion Date :
Oct 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cisplatin / Irinotecan / Radiation therapy (Arm A)

Days 1 - 35 : Concurrent radiation therapy (RT) and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles

Drug: cisplatin
Days 1 - 35 : Cisplatin 30 mg/m² days 1, 8, 15, 22, 29 Days 63 - 77 : cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles
Other Names:
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
  • DDP
  • CDDP
  • DACP
  • NSC 119875
  • Drug: irinotecan hydrochloride
    Days 1 - 35 : Irinotecan 65 mg/m² days 1, 8, 22, 29 Days 63 - 77 : irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles
    Other Names:
  • Camptothecin-11
  • CPT-11
  • Camptosar
  • Procedure: conventional surgery
    The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.

    Radiation: radiation therapy
    The total dose to the prescription point was 4500 cGy given in 25 fractions. The patient was treated with one fraction per day with all fields treated per day. 180 cGy was delivered to the isocenter. If the dose to the supraclavicular fossa (SCF) was less than 4500 cGy, a localized photon or electron boost was allowed in order to increase the SCF dose to 4500 cGy, specified at 3 cm depth from the anterior skin surface.

    Experimental: Paclitaxel / Cisplatin / Radiation therapy (Arm B)

    Days 1 - 35 : Concurrent radiation therapy (RT) and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles.

    Drug: cisplatin
    Days 1 - 35 : Cisplatin 30 mg/m² days 1, 8, 15, 22, 29 Days 63 - 77 : cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles
    Other Names:
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
  • DDP
  • CDDP
  • DACP
  • NSC 119875
  • Drug: paclitaxel
    Days 1 - 35 : Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29 Days 63 - 77 : paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles
    Other Names:
  • Taxol
  • NSC 125973
  • Procedure: conventional surgery
    The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.

    Radiation: radiation therapy
    The total dose to the prescription point was 4500 cGy given in 25 fractions. The patient was treated with one fraction per day with all fields treated per day. 180 cGy was delivered to the isocenter. If the dose to the supraclavicular fossa (SCF) was less than 4500 cGy, a localized photon or electron boost was allowed in order to increase the SCF dose to 4500 cGy, specified at 3 cm depth from the anterior skin surface.

    Outcome Measures

    Primary Outcome Measures

    1. Pathologic Complete Response Rate [approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry]

      A patient would have achieved a pathologic complete response if no histopathological evidence of residual tumor is found in the resected esophageal specimen and nodal tissue.

    Secondary Outcome Measures

    1. Overall Survival Time [Approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry]

      Survival was measured from the date of randomization onto study to death from any cause.Patients who were still alive at the end of the study were censored at the last date of known alive. Median survival time was calculated in the 81 eligible and treated patients.

    2. Recurrence-free Survival Time [Approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry]

      Recurrence-free survival is measured from the date of complete response to recurrence of the cancer. Patients without recurrence were censored at the last date of known recurrence-free. Median recurrence-free survival time was calculated in the eligible and treated patients.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Newly diagnosed adenocarcinoma of the esophagus (20 cm below incisors) or gastroesophageal junction

    • Stage T2-3, N0, M0 OR

    • Stage T1-3, N0-1, M0 or M1A (celiac nodal metastasis)

    • Tumor must be considered surgically resectable (T1-3, but not T4)

    • Age>=18 years

    • ECOG Performance status 0-1

    • Adequate hematopoietic, hepatic, renal functions defined by the following within 4 weeks prior to randomization:

    • Granulocyte count at least 1,000/mm^3

    • Platelet count at least 100,000/mm^3

    • Bilirubin no greater than 1.5 mg/dL

    • Creatinine clearance at least 60 mL/min

    • Prior curatively treated malignancy allowed if currently disease-free and survival prognosis is more than 5 years

    • Fertile patients must use effective contraception

    • Endoscopy with biopsy and dilation allowed

    Exclusion Criteria:
    • Tumor extends more than 2 cm into the cardia

    • Pregnant or nursing

    • Other concurrent illness that would preclude study therapy or surgical resection

    • Concurrent filgrastim (G-CSF) during study radiotherapy

    • Prior chemotherapy

    • Prior radiotherapy

    • Prior surgery

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CCOP - Colorado Cancer Research Program, Incorporated Denver Colorado United States 80224
    2 CCOP - Christiana Care Health Services Newark Delaware United States 19713
    3 Shands Cancer Center at the University of Florida Health Science Center Gainesville Florida United States 32610-100277
    4 Veterans Affairs Medical Center - Lakeside Chicago Chicago Illinois United States 60611-4494
    5 Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois United States 60611
    6 CCOP - Carle Cancer Center Urbana Illinois United States 61801
    7 CCOP - Iowa Oncology Research Association Des Moines Iowa United States 50309-1016
    8 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231
    9 CCOP - Michigan Cancer Research Consortium Ann Arbor Michigan United States 48106
    10 Mayo Clinic Cancer Center Rochester Minnesota United States 55905
    11 CCOP - Metro-Minnesota Saint Louis Park Minnesota United States 55416
    12 St. Joseph's Hospital Saint Paul Minnesota United States 55102
    13 Cancer Institute of New Jersey at Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
    14 Ireland Cancer Center Cleveland Ohio United States 44106-5065
    15 MetroHealth's Cancer Care Center at MetroHealth Medical Center Cleveland Ohio United States 44109
    16 CCOP - Toledo Community Hospital Toledo Ohio United States 43623-3456
    17 CCOP - MainLine Health Wynnewood Pennsylvania United States 19096
    18 Lankenau Cancer Center at Lankenau Hospital Wynnewood Pennsylvania United States 19096
    19 CCOP - Sioux Community Cancer Consortium Sioux Falls South Dakota United States 57104
    20 CCOP - Scott and White Hospital Temple Texas United States 76508
    21 CCOP - St. Vincent Hospital Cancer Center, Green Bay Green Bay Wisconsin United States 54307-3453
    22 University of Wisconsin Comprehensive Cancer Center Madison Wisconsin United States 53792-0001
    23 CCOP - Marshfield Clinic Research Foundation Marshfield Wisconsin United States 54449

    Sponsors and Collaborators

    • Eastern Cooperative Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Larry Kleinberg, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eastern Cooperative Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00033657
    Other Study ID Numbers:
    • CDR0000069309
    • U10CA021115
    • E1201
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Dec 3, 2012
    Last Verified:
    Nov 1, 2012

    Study Results

    Participant Flow

    Recruitment Details E1201 opened to accrual on May 21, 2002 and accrued its first patient on August 15, 2002. A total of 97 patients were accrued from 19 different participating sites.
    Pre-assignment Detail
    Arm/Group Title Cisplatin / Irinotecan / RT (Arm A) Paclitaxel / Cisplatin / RT (Arm B)
    Arm/Group Description Days 1 - 35 : Concurrent radiation therapy and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Days 1 - 35 : Concurrent RT and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles.
    Period Title: Neoadjuvant Chemotherapy
    STARTED 50 47
    Eligible 42 43
    Eligible and Treated 39 42
    COMPLETED 36 36
    NOT COMPLETED 14 11
    Period Title: Neoadjuvant Chemotherapy
    STARTED 36 36
    COMPLETED 36 33
    NOT COMPLETED 0 3
    Period Title: Neoadjuvant Chemotherapy
    STARTED 36 33
    COMPLETED 18 16
    NOT COMPLETED 18 17

    Baseline Characteristics

    Arm/Group Title Cisplatin / Irinotecan / RT (Arm A) Paclitaxel / Cisplatin / RT (Arm B) Total
    Arm/Group Description Days 1 - 35 : Concurrent radiation therapy and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Days 1 - 35 : Concurrent RT and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles. Total of all reporting groups
    Overall Participants 39 42 81
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.2
    (9.7)
    59.9
    (10.7)
    58.1
    (10.3)
    Sex: Female, Male (Count of Participants)
    Female
    4
    10.3%
    7
    16.7%
    11
    13.6%
    Male
    35
    89.7%
    35
    83.3%
    70
    86.4%
    Region of Enrollment (participants) [Number]
    United States
    39
    100%
    42
    100%
    81
    100%

    Outcome Measures

    1. Primary Outcome
    Title Pathologic Complete Response Rate
    Description A patient would have achieved a pathologic complete response if no histopathological evidence of residual tumor is found in the resected esophageal specimen and nodal tissue.
    Time Frame approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry

    Outcome Measure Data

    Analysis Population Description
    Eligible, treated patients
    Arm/Group Title Cisplatin / Irinotecan / RT (Arm A) Paclitaxel / Cisplatin / RT (Arm B)
    Arm/Group Description Days 1 - 35 : Concurrent radiation therapy and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Days 1 - 35 : Concurrent RT and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles.
    Measure Participants 39 42
    Number (90% Confidence Interval) [percentage of participants]
    15.4
    39.5%
    16.7
    39.8%
    2. Secondary Outcome
    Title Overall Survival Time
    Description Survival was measured from the date of randomization onto study to death from any cause.Patients who were still alive at the end of the study were censored at the last date of known alive. Median survival time was calculated in the 81 eligible and treated patients.
    Time Frame Approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry

    Outcome Measure Data

    Analysis Population Description
    Eligible, treated patients
    Arm/Group Title Cisplatin / Irinotecan / RT (Arm A) Paclitaxel / Cisplatin / RT (Arm B)
    Arm/Group Description Days 1 - 35 : Concurrent radiation therapy and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Days 1 - 35 : Concurrent RT and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles.
    Measure Participants 39 42
    Median (95% Confidence Interval) [Months]
    35.0
    21.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cisplatin / Irinotecan / RT (Arm A), Paclitaxel / Cisplatin / RT (Arm B)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.48
    Comments
    Method Log Rank
    Comments
    3. Secondary Outcome
    Title Recurrence-free Survival Time
    Description Recurrence-free survival is measured from the date of complete response to recurrence of the cancer. Patients without recurrence were censored at the last date of known recurrence-free. Median recurrence-free survival time was calculated in the eligible and treated patients.
    Time Frame Approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cisplatin / Irinotecan / RT (Arm A) Paclitaxel / Cisplatin / RT (Arm B)
    Arm/Group Description Days 1 - 35 : Concurrent radiation therapy and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Days 1 - 35 : Concurrent RT and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles.
    Measure Participants 39 42
    Median (95% Confidence Interval) [Months]
    39.8
    12.4

    Adverse Events

    Time Frame Reported 4-6 weeks after the end of pre-op chemotherapy/RT, (just prior to resection) and 4 weeks after the end of adjuvant chemotherapy
    Adverse Event Reporting Description
    Arm/Group Title Neoadjuvant_Cisplatin / Irinotecan / RT (Arm A) Neoadjuvant_Paclitaxel / Cisplatin / RT (Arm B) Adjuvant_Cisplatin / Irinotecan / RT ( Arm A) Adjuvant_Paclitaxel / Irinotecan / RT ( Arm B)
    Arm/Group Description Days 1 - 35 : Concurrent radiation therapy and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Days 1 - 35 : Concurrent RT and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles. Adjuvant chemotherapy toxicities in treated patients
    All Cause Mortality
    Neoadjuvant_Cisplatin / Irinotecan / RT (Arm A) Neoadjuvant_Paclitaxel / Cisplatin / RT (Arm B) Adjuvant_Cisplatin / Irinotecan / RT ( Arm A) Adjuvant_Paclitaxel / Irinotecan / RT ( Arm B)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Neoadjuvant_Cisplatin / Irinotecan / RT (Arm A) Neoadjuvant_Paclitaxel / Cisplatin / RT (Arm B) Adjuvant_Cisplatin / Irinotecan / RT ( Arm A) Adjuvant_Paclitaxel / Irinotecan / RT ( Arm B)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 32/47 (68.1%) 30/46 (65.2%) 20/31 (64.5%) 15/27 (55.6%)
    Blood and lymphatic system disorders
    Transfusion:PRBCS 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Thrombosis/Embolism 1/47 (2.1%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Febrile neutropenia 2/47 (4.3%) 2/46 (4.3%) 1/31 (3.2%) 2/27 (7.4%)
    Anemia 0/47 (0%) 0/46 (0%) 1/31 (3.2%) 0/27 (0%)
    Cardiac disorders
    Sinus bradycardia 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Chest pain 1/47 (2.1%) 0/46 (0%) 0/31 (0%) 0/27 (0%)
    Gastrointestinal disorders
    Constipation 1/47 (2.1%) 0/46 (0%) 0/31 (0%) 0/27 (0%)
    Dysphagia 0/47 (0%) 1/46 (2.2%) 1/31 (3.2%) 0/27 (0%)
    Nausea 11/47 (23.4%) 6/46 (13%) 1/31 (3.2%) 3/27 (11.1%)
    Vomiting 4/47 (8.5%) 4/46 (8.7%) 3/31 (9.7%) 4/27 (14.8%)
    Diarrhea w/o prior colostomy 4/47 (8.5%) 1/46 (2.2%) 5/31 (16.1%) 3/27 (11.1%)
    Abdominal pain 1/47 (2.1%) 0/46 (0%) 2/31 (6.5%) 0/27 (0%)
    General disorders
    Fatigue 2/47 (4.3%) 5/46 (10.9%) 2/31 (6.5%) 2/27 (7.4%)
    Fever 0/47 (0%) 1/46 (2.2%) 1/31 (3.2%) 0/27 (0%)
    Pain-other 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Hepatobiliary disorders
    AST increased 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    ALT increased 1/47 (2.1%) 1/46 (2.2%) 0/31 (0%) 1/27 (3.7%)
    Infections and infestations
    Infection w/o neutropenia 1/47 (2.1%) 0/46 (0%) 1/31 (3.2%) 0/27 (0%)
    Injury, poisoning and procedural complications
    Dysphagia-esophageal radiation 6/47 (12.8%) 8/46 (17.4%) 0/31 (0%) 1/27 (3.7%)
    Mucositis due to radiation 1/47 (2.1%) 0/46 (0%) 0/31 (0%) 0/27 (0%)
    Pain due to radiation 2/47 (4.3%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Dysphagia-pharyngeal radiation 0/47 (0%) 0/46 (0%) 0/31 (0%) 1/27 (3.7%)
    Investigations
    Leukopenia 17/47 (36.2%) 16/46 (34.8%) 15/31 (48.4%) 6/27 (22.2%)
    Lymphopenia 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 1/27 (3.7%)
    Neutropenia 15/47 (31.9%) 13/46 (28.3%) 16/31 (51.6%) 8/27 (29.6%)
    Thrombocytopenia 1/47 (2.1%) 1/46 (2.2%) 1/31 (3.2%) 0/27 (0%)
    Weight loss 1/47 (2.1%) 1/46 (2.2%) 3/31 (9.7%) 3/27 (11.1%)
    Bilirubin increased 1/47 (2.1%) 0/46 (0%) 1/31 (3.2%) 0/27 (0%)
    Creatinine increased 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Metabolism and nutrition disorders
    Anorexia 9/47 (19.1%) 2/46 (4.3%) 5/31 (16.1%) 2/27 (7.4%)
    Dehydration 4/47 (8.5%) 4/46 (8.7%) 1/31 (3.2%) 4/27 (14.8%)
    Hyperglycemia 1/47 (2.1%) 2/46 (4.3%) 0/31 (0%) 2/27 (7.4%)
    Hypocalcemia 0/47 (0%) 2/46 (4.3%) 0/31 (0%) 0/27 (0%)
    Hypokalemia 1/47 (2.1%) 1/46 (2.2%) 0/31 (0%) 1/27 (3.7%)
    Hypomagnesemia 1/47 (2.1%) 1/46 (2.2%) 0/31 (0%) 1/27 (3.7%)
    Hyponatremia 0/47 (0%) 4/46 (8.7%) 1/31 (3.2%) 1/27 (3.7%)
    Hypophosphatemia 1/47 (2.1%) 0/46 (0%) 0/31 (0%) 0/27 (0%)
    Nervous system disorders
    Dizziness/lightheadedness 1/47 (2.1%) 0/46 (0%) 0/31 (0%) 0/27 (0%)
    Neuropathy-motor 1/47 (2.1%) 0/46 (0%) 0/31 (0%) 0/27 (0%)
    Syncope 1/47 (2.1%) 0/46 (0%) 1/31 (3.2%) 1/27 (3.7%)
    Tremor 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Neuropathic pain 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Renal and urinary disorders
    Urinary electrolyte wasting 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Reproductive system and breast disorders
    Erectile impotence 0/47 (0%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/47 (0%) 0/46 (0%) 0/31 (0%) 1/27 (3.7%)
    Vascular disorders
    Hypertension 1/47 (2.1%) 0/46 (0%) 0/31 (0%) 0/27 (0%)
    Hypotension 2/47 (4.3%) 1/46 (2.2%) 0/31 (0%) 0/27 (0%)
    Other (Not Including Serious) Adverse Events
    Neoadjuvant_Cisplatin / Irinotecan / RT (Arm A) Neoadjuvant_Paclitaxel / Cisplatin / RT (Arm B) Adjuvant_Cisplatin / Irinotecan / RT ( Arm A) Adjuvant_Paclitaxel / Irinotecan / RT ( Arm B)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 47/47 (100%) 46/46 (100%) 30/31 (96.8%) 25/27 (92.6%)
    Blood and lymphatic system disorders
    Anemia 38/47 (80.9%) 40/46 (87%) 28/31 (90.3%) 22/27 (81.5%)
    Ear and labyrinth disorders
    Inner ear/hearing imparied 2/47 (4.3%) 2/46 (4.3%) 2/31 (6.5%) 1/27 (3.7%)
    Gastrointestinal disorders
    Constipation 10/47 (21.3%) 12/46 (26.1%) 3/31 (9.7%) 2/27 (7.4%)
    Dyspepsia 7/47 (14.9%) 4/46 (8.7%) 3/31 (9.7%) 1/27 (3.7%)
    Dysphagia 4/47 (8.5%) 4/46 (8.7%) 1/31 (3.2%) 2/27 (7.4%)
    Mouth dryness 3/47 (6.4%) 3/46 (6.5%) 1/31 (3.2%) 2/27 (7.4%)
    Nausea 26/47 (55.3%) 30/46 (65.2%) 19/31 (61.3%) 14/27 (51.9%)
    Stomatitis 3/47 (6.4%) 8/46 (17.4%) 0/31 (0%) 0/27 (0%)
    Taste disturbance 9/47 (19.1%) 15/46 (32.6%) 8/31 (25.8%) 10/27 (37%)
    Vomiting 20/47 (42.6%) 16/46 (34.8%) 10/31 (32.3%) 9/27 (33.3%)
    Diarrhea w/o prior colostomy 17/47 (36.2%) 16/46 (34.8%) 14/31 (45.2%) 13/27 (48.1%)
    Abonominal pain 8/47 (17%) 7/46 (15.2%) 5/31 (16.1%) 7/27 (25.9%)
    Flatulence 1/47 (2.1%) 0/46 (0%) 3/31 (9.7%) 1/27 (3.7%)
    General disorders
    Edema 1/47 (2.1%) 4/46 (8.7%) 1/31 (3.2%) 0/27 (0%)
    Fatigue 32/47 (68.1%) 33/46 (71.7%) 23/31 (74.2%) 19/27 (70.4%)
    Hepatobiliary disorders
    AST increased 5/47 (10.6%) 9/46 (19.6%) 2/31 (6.5%) 3/27 (11.1%)
    ALT increased 17/47 (36.2%) 17/46 (37%) 5/31 (16.1%) 6/27 (22.2%)
    Injury, poisoning and procedural complications
    Radiation dermatitis 8/47 (17%) 6/46 (13%) 0/31 (0%) 0/27 (0%)
    Dysphagia-esophageal radiation 18/47 (38.3%) 21/46 (45.7%) 3/31 (9.7%) 2/27 (7.4%)
    Dysphagia-pharyngeal radiation 7/47 (14.9%) 2/46 (4.3%) 1/31 (3.2%) 0/27 (0%)
    Investigations
    Leukopenia 44/47 (93.6%) 41/46 (89.1%) 27/31 (87.1%) 17/27 (63%)
    Neutropenia 35/47 (74.5%) 24/46 (52.2%) 23/31 (74.2%) 9/27 (33.3%)
    Thrombocytopenia 31/47 (66%) 29/46 (63%) 21/31 (67.7%) 8/27 (29.6%)
    Weight loss 19/47 (40.4%) 17/46 (37%) 15/31 (48.4%) 10/27 (37%)
    Alkaline phosphatase increased 10/47 (21.3%) 7/46 (15.2%) 10/31 (32.3%) 7/27 (25.9%)
    Bilirubin increased 4/47 (8.5%) 6/46 (13%) 1/31 (3.2%) 0/27 (0%)
    Creatinine increased 8/47 (17%) 12/46 (26.1%) 3/31 (9.7%) 8/27 (29.6%)
    Metabolism and nutrition disorders
    Anorexia 21/47 (44.7%) 18/46 (39.1%) 11/31 (35.5%) 14/27 (51.9%)
    Dehydration 6/47 (12.8%) 12/46 (26.1%) 4/31 (12.9%) 2/27 (7.4%)
    Hypoalbuminemia 4/47 (8.5%) 4/46 (8.7%) 1/31 (3.2%) 1/27 (3.7%)
    Hyperglycemia 7/47 (14.9%) 9/46 (19.6%) 3/31 (9.7%) 3/27 (11.1%)
    Hypocalcemia 6/47 (12.8%) 6/46 (13%) 2/31 (6.5%) 0/27 (0%)
    Hypokalemia 5/47 (10.6%) 4/46 (8.7%) 3/31 (9.7%) 3/27 (11.1%)
    Hypomagnesemia 3/47 (6.4%) 7/46 (15.2%) 4/31 (12.9%) 1/27 (3.7%)
    Hyponatremia 2/47 (4.3%) 9/46 (19.6%) 2/31 (6.5%) 1/27 (3.7%)
    Musculoskeletal and connective tissue disorders
    Myalgia 1/47 (2.1%) 3/46 (6.5%) 0/31 (0%) 2/27 (7.4%)
    Arthralgia 0/47 (0%) 0/46 (0%) 0/31 (0%) 3/27 (11.1%)
    Nervous system disorders
    Dizziness/lightheadedness 5/47 (10.6%) 11/46 (23.9%) 2/31 (6.5%) 2/27 (7.4%)
    Neuropathy-sensory 4/47 (8.5%) 7/46 (15.2%) 3/31 (9.7%) 12/27 (44.4%)
    Psychiatric disorders
    Insomnia 4/47 (8.5%) 2/46 (4.3%) 1/31 (3.2%) 2/27 (7.4%)
    Anxiety/agitation 3/47 (6.4%) 4/46 (8.7%) 1/31 (3.2%) 3/27 (11.1%)
    Renal and urinary disorders
    Dysuria 1/47 (2.1%) 3/46 (6.5%) 1/31 (3.2%) 0/27 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 5/47 (10.6%) 4/46 (8.7%) 2/31 (6.5%) 1/27 (3.7%)
    Allergic rhinitis 2/47 (4.3%) 0/46 (0%) 3/31 (9.7%) 0/27 (0%)
    Cough 2/47 (4.3%) 2/46 (4.3%) 2/31 (6.5%) 3/27 (11.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 12/47 (25.5%) 13/46 (28.3%) 10/31 (32.3%) 14/27 (51.9%)
    Rash/desquamation 0/47 (0%) 4/46 (8.7%) 1/31 (3.2%) 1/27 (3.7%)
    Vascular disorders
    Hypotension 1/47 (2.1%) 1/46 (2.2%) 2/31 (6.5%) 0/27 (0%)

    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.

    Results Point of Contact

    Name/Title Study Statistician
    Organization Eastern Cooperative Oncology Group (ECOG) Statistical Office
    Phone 617-632-3012
    Email
    Responsible Party:
    Eastern Cooperative Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00033657
    Other Study ID Numbers:
    • CDR0000069309
    • U10CA021115
    • E1201
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Dec 3, 2012
    Last Verified:
    Nov 1, 2012