Patients with any uncontrolled concurrent selleck products medical condition, known malabsorption syndrome, or who had participated in an investigational drug study within 4 weeks were also excluded from participation in the study. Randomisation, stratification and treatment The ATTAX study was a randomised, phase II, open-label, multicentre study of wTCF or wTX. Randomisation was carried out centrally at the coordinating centre, and patients were stratified by WHO PS (0, 1 vs 2) and institution. Patients were randomly assigned in equal proportions to receive either docetaxel (Taxotere; Sanofi-Aventis, Paris, France) (30mgm?2) on days 1 and 8, cisplatin (60mgm?2) on day 1, and 5-fluorouracil (200mgm?2 per day) by continuous infusion, every 3 weeks (wTCF); or docetaxel (30mgm?2) on days 1 and 8 and oral capecitabine (Xeloda; Roche, Basel, Switzerland) (800mgm?2) twice daily on days 1�C14, every 3 weeks (wTX).

The dosages were selected for the combination regimens with reference to earlier phase I or II studies (Chen et al, 2002; Lee et al, 2006; Mrozek et al, 2006). Premedication of dexamethasone (8mg) was given before docetaxel administration, and cisplatin hydration was given according to each investigator’s routine practice. Dose-modification criteria were defined in the protocol. Treatment continued for eight cycles in the absence of disease progression, any request by the patient or physician to discontinue therapy, unacceptable toxicity, pregnancy, or serious systemic allergic reaction to any of the study drugs.

At the investigator’s discretion, patients with no disease progression or grade III or IV toxicity could continue beyond eight cycles. Patients in the wTCF arm experiencing auditory or peripheral neurotoxicity or renal impairment, thought to be related to cisplatin, were allowed to substitute carboplatin for cisplatin. Evaluation and outcomes Before randomisation, each patient was assessed by complete physical examination, full blood count, clotting profile, blood biochemistry, tumour markers (carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19.9)), 12-lead electrocardiogram, contrast-enhanced CT scan of the thorax, abdomen, and pelvis, and a pregnancy test for women of child-bearing potential. Subsequently, complete physical examination, blood biochemistry, and a toxicity and adverse event assessment were repeated before each cycle began; a full blood count was repeated before every docetaxel infusion.

A tumour marker assessment and contrast-enhanced CT scan of the thorax, abdomen, and pelvis were repeated at the end of every second treatment cycle, then 12-weekly until disease progression. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Brefeldin_A (NCI CTCAE), version 3.0. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ) C30, version 3.