Page 69 - Demo

Vitamin B12 and folic acid in advanced oesophageal and gastric cancer674life expectancy of at least 12 weeks, adequate bone marrow function, adequate renal function, and adequate hepatic function. Prior surgery, chemotherapy and/or radiotherapy in the neo-adjuvant or adjuvant setting was allowed as long as the chemotherapy was completed at least 6 months prior to entry of the study. Written informed consent was obtained from all patients prior to inclusion into the study. Patients with known symptomatic metastasis in the central nervous system (CNS) or suffering from any serious concomitant systemic disorders incompatible with study treatment were not eligible. Other exclusion criteria were treatment with any investigational agent in the month prior to inclusion or prior diagnosis of other malignant disease (excluding adequately treated in situ carcinoma of the cervix and non-melanoma skin cancer, low grade prostate carcinoma or any other non-relapsed malignancy that was treated more than five years before diagnosis). Randomization was performed by the datamanagement center of the Integraal Kanker Center Amsterdam (IKA) using a computerized randomization system. The institutional Medical Ethical board of the VUmc and Noordwest Ziekenhuisgroep approved the trial, which was in accordance with the Declaration of Helsinki and Good Clinical Practice. Study treatmentPatients were randomized to receive treatment with gemcitabine 1250 mg/m2intravenously (i.v.) on days 1 and 8 in combination with cisplatin 80 mg/m2 i.v. on day 1 in a 3 weekly cycle with or without vitamin supplementation, further described as supplemented vs unsupplemented patients, respectively. Vitamin supplementation consisted of folic acid 450 %u03bcg/24 h per os (p.o., starting at least one week prior to chemotherapy and finishing at least 3 weeks after the last treatment dose, and vitamin B12 1000 %u03bcg (1 vial intramuscularly, i.m.) every 9 weeks, starting 1 week before chemotherapy and finishing at least 3 weeks after the last treatment dose. Patients were treated with up to 6 cycles of chemotherapy. Study treatment was discontinued in case of progressive disease, unacceptable toxicity or upon patient request.EndpointsThe primary endpoint of this study was to determine whether supplementation of folic acid and vitamin B12 could increase the response rate (RR) of patients with