Combination Treatment of S-1 With Paclitaxel Versus Paclitaxel+Cisplatin and 5-Fu+Cisplatin as First-line Treatment in Advanced Esophageal Cancer
Esophageal cancer is one of the common malignant tumors, especially in China and the annual
incidence of esophageal squamous cell carcinoma is 260,000 with the motility of 210,000. In
western countries, the incidence of esophageal adenocarcinoma (esophageal - gastric junction
carcinoma) now dramatically increased than in the past. The pathological types of highest
incidences are changing from esophageal squamous cell carcinoma (Esophageal Squamous Cell
Carcinoma, ESCC) to esophageal adenocarcinoma (Esophageal adenocarcinoma, EAC) whose
incidence is about 60-70%. But in Asia, esophageal squamous cell carcinoma is still the
dominant pathological type, accounting for more than 95%. The prognosis of esophageal cancer
is very poor. About 50% of patients have advanced disease at diagnosis and the natural
course is only 6-8 months with a 5-year survival rate of 5-7%. In addition, though some
patients received surgical treatment, disease will recurrent and metastasis in nearly 90% of
the patients. For those patients in early stage (T1), there are still nearly 50% of
patients relapse within 5 years. Therefore, in recent years, doctors and researchers in
different countries are continued to seek effective treatment to improve the quality of life
of patients with esophageal cancer and prolong survival.
In past decades, there isn't much improvement of the outcome and survival of advanced
esophageal cancer due to the lack of effective chemotherapy agents. The traditional
chemotherapy drugs to treat esophageal cancer include 5 - fluorouracil and cisplatin and the
combination of them results in a 25-35% response rate in both first-line and palliative
treatment. And this combing is still the traditional chemotherapy regimens and wildly used
in clinical studies to treat both esophageal gland, squamous cell carcinoma of the clinical
Paclitaxel plus cisplatin regiment is another promising treatment of esophageal cancer and
have been proved effective in a lot of studies. This combination has become a standard
treatment of esophageal cancer, especially the esophageal squamous cell carcinoma. In one of
our previous study, paclitaxel and cisplatin treatment showed encouraging clinical results
with manageable side-effects in 131 patients of advanced esophageal cancer. These
investigations have fully proved the efficacy and feasibility of the combination of
paclitaxel with cisplatin regiment in the treatment of esophageal cancer. However, the lower
solubility of paclitaxel limited its direct intravenous use. To solve this problem, the
paclitaxel must inject with an addition of the surfactant polyoxyethylene castor oil.
Polyoxyethylene castor oil paclitaxel could induce high incidence of acute hypersensitivity
reactions, ie. severe allergic reactions, kidney damage, and neurotoxicity and
cardiovascular toxicity which is characterized by axonal degeneration and demyelination.
Though proper preventive treatment will greatly reduce the incidence of allergy, there are
still a small number of patients have allergy reaction.
As the investigators all know, the main adverse of cisplatin is the renal toxicity. The peak
age of esophageal cancer patients are age 65 to 70 and many of them have simultaneously
other diseases such as hypertension, diabetes, and chronic kidney disease which cause
varying damages of renal function and limit the use of cisplatin in these patients.
Therefore, it is urgent and crucial for doctors to seek an alternative of cisplatin in the
combination chemotherapy treatment. There haven't well designed large scale clinical trials
to evidence the non-platinum treatment in esophageal cancer. Therefore, the investigators
designed this randomized clinical trial in which a novel combination of S-1 with paclitaxel
is used to treat advanced esophageal cancer patients in compare with paclitaxel/cisplatin
and 5-FU/cisplatin treatment to explore its efficacy and toxicity. The investigators hope
this study will provide some clues for the treatment of esophageal cancer patients.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
The disease control rate (DCR) will be evaluated every 2 cycles (average 6 weeks) of treatment according to the RECIST 1.0 criteria until disease progression or finishing all 6 cycles of treatment.
Every 2 cycles of treatment (average 6 weeks) up to 6cycles (assessed 18 weeks)
Xiaodong Zhang, MD
Beijing Cancer Hospital, Peking University Cancer Hospital
China: Food and Drug Administration