Efficacy Comparison Study of Combination Regimens to Treat Advanced Esophageal Squamous Cell Carcinoma

Until today, the 5-FU/cisplatin combination is the reference regimen with 30-45% response rates, which is most commonly used to treat patients with metastatic, recurrent or locally advanced, unresectable squamous cell carcinoma of the esophagus. Because the classical dose schedule of this two-drug combination is cisplatin 100 mg/m2 day 1 and 5-FU 1000 mg/m2/day continuous infusion for 96-120 hr, prolonged administration time and mucosal toxicity are inconvenient to the patients with the aim of palliation. Capecitabine, which is oral prodrug of 5-FU and mimic continuously-infused 5-FU, is being investigated in phase I, II and III trials for the treatment of gastric, gastroesophageal, and esophageal cancers, primarily in the first-line metastatic setting. In our experience, capecitabine plus cisplatin combination (XP) as a first-line treatment for 45 patients with advanced or recurrent esophageal squamous cell carcinoma demonstrated a promising anti-tumor activity with 57% of response rate and showed tolerable toxicity with convenience. Paclitaxel has been also investigated as monotherapy and in combination with cisplatin in patients with advanced esophageal cancer. A Dutch phase II study demonstrated that paclitaxel combination with carboplatin had shown an encouraging confirmed response rate of 59% with 51 patients with resectable esophageal cancer in neoadjuvant setting. Another Dutch phase II study showed 43% of response rate including 4% of CR with 8 months of response duration when paclitaxel plus cisplatin administration was given for patients with metastatic esophageal cancer. Although recently first-line palliative chemotherapy regimen in esophageal cancer has been investigated, many trials have failed to show superiority to 5-FU/cisplatin combination. Since we considered that XP or XT is more effective and convenient chemotherapy regimen than 5-FU/cisplatin, this randomized phase II study was planned to compare XP with XT in terms of efficacy and tolerability.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Histologically confirmed metastatic, or recurrent esophageal squamous cell carcinoma
2. Age \> 18 years
3. ECOG performance status 0 - 2
4. At least one measurable lesion(s) by RECIST criteria
5. Life expectancy ≥ 3 months
6. Patients may have received prior adjuvant chemotherapy with 5-FU with cisplatin as long as it has been 12 months since completion of regimen.
7. No previous palliative chemotherapy
8. Prior radiotherapy must be completed 4 weeks before study entry.
9. Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)
10. Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 50 ml/min)
11. Adequate liver function (≤ serum bilirubin 1.5 mg/dl, ≤ AST/ALT x 3 upper normal limit)
12. Written informed consent

Exclusion Criteria:

1. Other tumor types such as adenocarcinoma, small cell carcinoma
2. Evidence of CNS metastasis
3. Contraindication to any drug contained in the chemotherapy regimen
4. Previous adjuvant treatment with 5-FU, cisplatin, capecitabine or paclitaxel finished less than 1 year
5. Evidence of serious gastrointestinal bleeding
6. History of another malignancy within the last five years except cured basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix
7. Clinically significant cardiac disease (e.g. severe non-compensated hypertension, non-compensated heart failure, dilated cardiomyopathy, and coronary heart disease with ST segment depression in ECG) or myocardial infarction within the last 6 months.
8. Serious pulmonary conditions/illness (e.g. chronic lung disease with hypoxemia)
9. Serious metabolic disease such as severe non-compensated diabetes mellitus
10. History of significant neurologic or psychiatric disorders
11. Serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease
12. Positive serology for the HIV
13. Pregnant or lactating women