Esophageal Cancer, Gastric Cancer
Conditions
Keywords
stage I gastric cancer, stage II gastric cancer, stage III gastric cancer, stage IV gastric cancer, stage I esophageal cancer, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer, adenocarcinoma of the stomach, adenocarcinoma of the esophagus
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.
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.
Interventions
DRUGcisplatin
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
DRUGirinotecan 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
DRUGpaclitaxel
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
PROCEDUREconventional surgery
The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.
RADIATIONradiation 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.
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Cisplatin / Irinotecan / RT (Arm A) 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 | 39 |
| Paclitaxel / Cisplatin / RT (Arm B) 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. | 42 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Adjuvant Chemotherapy | Adverse Event | 7 | 10 |
| Adjuvant Chemotherapy | alternative therapy | 1 | 0 |
| Adjuvant Chemotherapy | Death | 2 | 1 |
| Adjuvant Chemotherapy | Lack of Efficacy | 3 | 1 |
| Adjuvant Chemotherapy | Other | 0 | 2 |
| Adjuvant Chemotherapy | Withdrawal by Subject | 5 | 3 |
| Neoadjuvant Chemotherapy | Adverse Event | 0 | 2 |
| Neoadjuvant Chemotherapy | Death | 1 | 1 |
| Neoadjuvant Chemotherapy | Ineligible | 8 | 4 |
| Neoadjuvant Chemotherapy | Lack of Efficacy | 1 | 2 |
| Neoadjuvant Chemotherapy | Not started protocol therapy | 3 | 1 |
| Neoadjuvant Chemotherapy | other complicating disease | 0 | 1 |
| Neoadjuvant Chemotherapy | Withdrawal by Subject | 1 | 0 |
| Surgical Resection | not complete resection | 0 | 3 |
Baseline characteristics
| Characteristic | Cisplatin / Irinotecan / RT (Arm A) | Paclitaxel / Cisplatin / RT (Arm B) | Total |
|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 9.7 | 59.9 years STANDARD_DEVIATION 10.7 | 58.1 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment United States | 39 participants | 42 participants | 81 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 35 Participants | 35 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 47 | 46 / 46 | 30 / 31 | 25 / 27 |
| serious Total, serious adverse events | 32 / 47 | 30 / 46 | 20 / 31 | 15 / 27 |
Outcome results
Primary
Pathologic Complete Response Rate
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
Population: Eligible, treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cisplatin / Irinotecan / RT (Arm A) | Pathologic Complete Response Rate | 15.4 percentage of participants |
| Paclitaxel / Cisplatin / RT (Arm B) | Pathologic Complete Response Rate | 16.7 percentage of participants |
Secondary
Overall Survival Time
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
Population: Eligible, treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cisplatin / Irinotecan / RT (Arm A) | Overall Survival Time | 35.0 Months |
| Paclitaxel / Cisplatin / RT (Arm B) | Overall Survival Time | 21.0 Months |
p-value: 0.48Log Rank
Secondary
Recurrence-free Survival Time
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cisplatin / Irinotecan / RT (Arm A) | Recurrence-free Survival Time | 39.8 Months |
| Paclitaxel / Cisplatin / RT (Arm B) | Recurrence-free Survival Time | 12.4 Months |