trial of docetaxel, oxaliplatin and capecitabine (tex) in advanced or metastatic gastric cancer

Conditions: Stomach Neoplasms

Summary: 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.


Eligibility criteria:
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

Keywords: stomach neoplasms docetaxel oxaliplatin capecitabine