Combination regimens of 3 active drugs have shown promising activity in treatment of metastatic gastric cancer. Docetaxel combined with cisplatin and 5-fluorouracil (FU) yielded superior overall survival and response rates when compared to standard cisplatin and 5-FU. However, a toxicity profile showed the need for development of less toxic modifications. In a prior phase I trial, the maximum tolerated dose was defined. In this phase II trial, a first evaluation of activity will be performed.

Inclusion Criteria:

• Written informed consent

• Histologically proven irresectable, metastatic or recurrent adenocarcinoma of the stomach or the gastroesophageal junction, i.e., Tx-4 M1 or T4 M0

• Irresectable (as judged by an experienced surgeon):

  1. T4 infiltrating of several organs
  2. T4 infiltrating one organ, but irresectable
  3. T4 infiltrating one organ, respectable, but inoperable patient

• The nodal status is neglected

• Measurable disease according to RECIST

• ECOG Performance Status ≤ 2

• Male or female patients aged ≥ 18 years

• Life expectancy ≥ 3 months

• Adequate bone marrow, hepatic and renal function:

  1. Haemoglobin > 9.0 g/dL (transfusions allowed to achieve or maintain levels)
  2. Absolute neutrophil count > 1.5 x 10^9/L
  3. Platelet count > 100 x 10^9/L
  4. ALAT, ASAT < 3.5 x ULN
  5. Alkaline phosphatase < 6 x ULN
  6. Total bilirubin < 1.0 x ULN
  7. Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)

• Prior surgery must be more than 28 days ago

• Positive nodes as diagnosed on endorectal ultrasound and/or MRI (tumour is staged by preferably a high resolution MRI; if MRI is not available, locoregional staging must be performed by computed tomography plus endorectal ultrasound)

• Tumor staging must be done within 28 days from the start of the treatment

• Negative pregnancy test in women with childbearing of potential (within 7 days prior to the start of the chemotherapy)

  • Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential

Exclusion Criteria:

• Prior cytotoxic chemotherapy or radiotherapy (a neoadjuvant or adjuvant chemotherapy must be completed and without progression for at least 6 months)

• Previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin

• Peripheral neuropathy ≥ grade 2 (according to NCI CTCAE v 3.0)

• Patient must not have been treated with any investigational drug, agent nor procedure, (i.e., did not participate in another trial within 30 days) before entry in this trial

• Known allergy or any other adverse reaction to any of the study drugs or to any related compound

• Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine

• Clinically significant concomitant diseases, such as:

  1. Active infection necessitating systemic antibiotics
  2. Interstitial lung diseases
  3. Chronic diarrhea, inflammatory bowel disease
  4. Neurological or psychiatric disease, dementia, epilepsy or untreated brain metastases

• Cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction or resuscitation within the last 6 months

• Pregnant or lactating women are excluded

• Presence of adequate contraception in fertile patients (methods of adequate contraception are: intra-uterine device, hormonal contraception, vasectomy, tubal ligation or abstinence)

• Alcohol or drug abuse

• Ability to swallow tablets

• Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule