Stomach Cancer
Conditions
Keywords
Stomach cancer, Adjuvant chemotherapy, Mitomycin, Cisplatin, Doxifluridine
Brief summary
This is a phase III randomized study designed to evaluate the efficacy of mitomycin, doxifluridine, and cisplatin compared to mitomycin and doxifluridine.
Detailed description
Stomach cancer is the most common cancer in Korea and one of the major health problems worldwide. The most effective treatment for gastric cancer is curative surgical resection of primary tumor. However, a substantial number of patients eventually die of recurrences after curative resection. A number of randomized trials investigating the role of adjuvant chemotherapy have been conducted. However, the efficacy of adjuvant chemotherapy is still controversial and varied between Western and Asian trials. Meta-analysis of Western trials didn't demonstrate the benefit of adjuvant chemotherapy after curative resection. Conversely, some Asian studies have demonstrated the efficacy of adjuvant chemotherapy after curative resection. In a previous study, mitomycin plus tegafur prolonged the survival in resected gastric cancer compared to no treatment. This study is designed to evaluate the efficacy of mitomycin, cisplatin and prolonged treatment with doxifluridine compared to mitomycin plus doxifluridine.
Interventions
DRUGMitomycin, doxifluridine and cisplatin
Mitomycin-C 20mg/m2 intravenously (day 1), Doxifluridine 460-600mg/m2/day per oral (day 28- day 336), Cisplatin 60mg/m2 intravenously (day 28, day 56, day 84, day 112, day 140, and day 168)
DRUGMitomycin and doxifluridine
Mitomycin-C 20mg/m2 intravenously (day 1), Doxifluridine 460-600mg/m2/day per oral (day 28-day 84)
Sponsors
Ulsan University Hospital
Hallym University Medical Center
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Pathologically proven gastric adenocarcinoma * Curative resection was done * stage II, IIIA, IIIB, IV (including T4, lesions or N3, but excluding M1 lymph node metastasis) * age: 18-69 years old * Performance status: ECOG 0-2 * Adequate bone marrow function (WBC ≥ 4,000/ul, platelet count ≥ 100,000/ul, hemoglobin ≥ 10 g/dl) * Adequate renal function (serum creatinine≤ 1.5) * Adequate liver function (serum bilirubin ≤1.5 mg/dl, AST/ALT ≤ 3 x normal upper limit) * Written informed consent was signed by the patient
Exclusion criteria
* Previous chemotherapy or radiotherapy * Active ongoing infection which antibiotic treatment is needed * Pregnant or lactating women * Psychosis or convulsion disorder * Ascites in preoperative abdomen CT * Systemic disease which interfere the administration of chemotherapy * Previous history of other malignancy except cured non-malignant skin cancer and uterine cervical cancer in situ
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free Survival Rate | 3 years | Relapse-free survival at 3 years was defined as the proportion of patients who did not show an evidence of disease recurrence after 3 years of surgery. Relapse was defined as any new tumor lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | 3 years | Overall survival rate at 3 years was defined as the proportion of patients who were alive at 3 years after surgery. |
| Number of Patients With Adverse Events | Up to 3 years | Per National Cancer Institute Common Toxicity Criteria version 2.0, up to 3 years |
Countries
South Korea
Participant flow
Recruitment details
AMC0201 was an open-label, prospective randomised phase 3 clinical trial conducted at three centres (Asan medical center, Hallym University medical center, and Ulsan university hospital) in Korea. Patients were enrolled between February 2002 and August 2006
Pre-assignment details
All enrolled patients received study treatments
Participants by arm
| Arm | Count |
|---|---|
| Mitomycin and Doxifluridine Mitomycin-C 20mg/m2 intravenously (day 1), Doxifluridine 460-600mg/m2/day per oral (day 28- day 336), Cisplatin 60mg/m2 intravenously (day 28, day 56, day 84, day 112, day 140, and day 168) | 424 |
| Mitomycin, Doxifluridine and Cisplatin Experimental armMitomycin-C 20mg/m2 intravenously (day 1), Doxifluridine 460-600mg/m2/day per oral (day 28- day 336), Cisplatin 60mg/m2 intravenously (day 28, day 56, day 84, day 112, day 140, and day 168) | 431 |
| Total | 855 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 27 |
| Overall Study | Lost to Follow-up | 7 | 33 |
| Overall Study | Physician Decision | 3 | 11 |
| Overall Study | Recurrence | 3 | 51 |
Baseline characteristics
| Characteristic | Mitomycin, Doxifluridine and Cisplatin | Mitomycin and Doxifluridine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 63 Participants | 114 Participants |
| Age, Categorical Between 18 and 65 years | 380 Participants | 361 Participants | 741 Participants |
| Age, Continuous | 53.3 years STANDARD_DEVIATION 10.1 | 53.3 years STANDARD_DEVIATION 10.6 | 53.3 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment Korea, Republic of | 431 participants | 424 participants | 855 participants |
| Sex: Female, Male Female | 137 Participants | 130 Participants | 267 Participants |
| Sex: Female, Male Male | 294 Participants | 294 Participants | 588 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 393 / 422 | 413 / 425 |
| serious Total, serious adverse events | 3 / 422 | 5 / 425 |
Outcome results
Primary
Relapse-free Survival Rate
Relapse-free survival at 3 years was defined as the proportion of patients who did not show an evidence of disease recurrence after 3 years of surgery. Relapse was defined as any new tumor lesion.
Time frame: 3 years
Population: Intention-to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mitomycin Plus Short-term Fluoropyrimidine | Relapse-free Survival Rate | 67.0 percentage of participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Relapse-free Survival Rate | 64.9 percentage of participants |
Secondary
Number of Patients With Adverse Events
Per National Cancer Institute Common Toxicity Criteria version 2.0, up to 3 years
Time frame: Up to 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mitomycin Plus Short-term Fluoropyrimidine | Number of Patients With Adverse Events | Thrombocytopenia | 101 participants |
| Mitomycin Plus Short-term Fluoropyrimidine | Number of Patients With Adverse Events | Diarrhea | 219 participants |
| Mitomycin Plus Short-term Fluoropyrimidine | Number of Patients With Adverse Events | Anemia | 393 participants |
| Mitomycin Plus Short-term Fluoropyrimidine | Number of Patients With Adverse Events | Nausea | 293 participants |
| Mitomycin Plus Short-term Fluoropyrimidine | Number of Patients With Adverse Events | Fatigue | 343 participants |
| Mitomycin Plus Short-term Fluoropyrimidine | Number of Patients With Adverse Events | Vomiting | 104 participants |
| Mitomycin Plus Short-term Fluoropyrimidine | Number of Patients With Adverse Events | Neutropenia | 262 participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Number of Patients With Adverse Events | Vomiting | 160 participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Number of Patients With Adverse Events | Neutropenia | 387 participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Number of Patients With Adverse Events | Anemia | 413 participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Number of Patients With Adverse Events | Thrombocytopenia | 156 participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Number of Patients With Adverse Events | Fatigue | 391 participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Number of Patients With Adverse Events | Diarrhea | 288 participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Number of Patients With Adverse Events | Nausea | 371 participants |
Secondary
Overall Survival Rate
Overall survival rate at 3 years was defined as the proportion of patients who were alive at 3 years after surgery.
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mitomycin Plus Short-term Fluoropyrimidine | Overall Survival Rate | 76.9 percentage of participants |
| Mitomycin Plus Long-term Fluoropyrimidine and Monthly Cisplati | Overall Survival Rate | 73.1 percentage of participants |