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Combination Treatment of S-1 With Paclitaxel Versus Paclitaxel+Cisplatin and 5-Fu+Cisplatin as First-line Treatment in Advanced Esophageal Cancer

Phase 2/Phase 3
18 Years
75 Years
Open (Enrolling)
Esophageal Cancer

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Trial Information

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.

Inclusion Criteria:

- Patients who have histologically confirmed diagnosis of esophageal cancer without
prior palliative treatment or an interval of at least 6 months from the last
operation, adjuvant radiation therapy and adjuvant chemotherapy. If patients received
adjuvant chemotherapy, paclitaxel and cisplatin must be excluded from the regiment or
the total dosage of cisplatin must be less than 300mg/m2.

- - Patients must be 18 to 75 years old and both genders are eligible.

- - Patients must have measurable or evaluable disease with at least one tumor mass
maximum diameter ≥10mm by multi-slice spiral CT or MR scan. If ordinary CT scan is
used the tumor mass maximum diameter must ≥ 2cm. Imaging exam must be performed
within 15 days from enrollment.

- - Patients must have an expected life expectancy of ≥ 3 months

- - Patients must have a performance status of ≥ 80 on the Karnofsky scale

- - Patients must have normal marrow function and the blood tests must be collected
within 7 days from enrollment with a hemoglobin (HGB) of ≥90g/L, an white blood cell
(WBC) counts of ≥4.0×109/L,a neutrophil count of ≥2.0×109/L, , a platelet count of
≥100×109/L, a total bilirubin (TBil) of ≤1.0 upper normal limitation (UNL), a
creatinine (Cr) of ≤ 1.0 UNL, alanine aminotransferase (ALAT) and aspartate
aminotransferase (ASAT) of ≤2.5 UNL, Alkaline phosphatase (AKP) ≤5.0 UNL. For
patients with liver metastasis, the ASAT/ALAT must be ≤5.0 UNL.

- - Patients must have normal electrocardiogram results and no history of congestive
heart failure.

- - Patients must be with good compliance and agree to accept follow-up of disease
progression and adverse events.

- - Patients must give written informed consent signed voluntarily by patients
themselves or their supervisors witted by doctors

Exclusion Criteria:

- Patients who have received prior palliative treatment or less than 6 months from the
last operation, adjuvant radiotherapy, adjuvant chemotherapy.

- Previous treatment regiment involve paclitaxel and S-1

- Tumor mass >10mm by CT or MR scan. The total area of metastatic tumor lesions in
liver is over 50% of whole liver or the total area of metastatic tumor lesions in
lung is over 25% of whole lung.

- Patients without measurable or evaluable disease, for example cavity effusion or
diffusive metastasis of organs.

- Patients with history of other tumors except for those of cervical carcinoma in situ
or skin basal cell carcinoma who had been completely treated and without relapse in
last 5 years.

- Patients with serious diseases such as congestive heart failure, uncontrolled
myocardial infarction and arrhythmia, liver failure and renal failure.

- Patients with only brain metastasis or bone metastasis

- Patients with chronic diarrhea

- Patients with neurological or psychiatric abnormalities including metastasis of the
central nervous system that affect cognitive.

- Pregnant or lactated women (premenopausal women must give urine pregnancy test before

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Description:

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.

Outcome Time Frame:

Every 2 cycles of treatment (average 6 weeks) up to 6cycles (assessed 18 weeks)

Safety Issue:


Principal Investigator

Xiaodong Zhang, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beijing Cancer Hospital, Peking University Cancer Hospital


China: Food and Drug Administration

Study ID:




Start Date:

August 2012

Completion Date:

July 2013

Related Keywords:

  • Esophageal Cancer
  • Esophageal cancer
  • Chemotherapy
  • Efficacy
  • Toxicity
  • Esophageal Diseases
  • Esophageal Neoplasms