Patients receive oral folic acid once daily on days -7 to 6. Patients also receive lometrexol IV over 30-60 seconds on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed up to 2 months after removal from study and then every 3 months thereafter.

Inhibition of clonogenic potential by the glycinamideribonucleosyl transformylase inhibitor (DDATHF, Lometrexol) was evaluated in vitro in a human ovarian carcinoma cell line, SW626. Simultaneous treatment with 100 uM hypoxanthine completely prevented the inhibition of clonogenic potential caused by 0.5 uM DDATHF. DDATHF blocked cells in the early-middle S-phases of the cell cycle, and there was a corresponding marked reduction in the rate of DNA synthesis after drug withdrawal. DDATHF cytotoxicity differed moderately when folic acid concentrations varied between 0.22 and 0 uM, suggesting that folic acid does not necessarily antagonise DDATHF anti-tumour activity. Folinic acid at a concentration as low as 0.1 uM can completely rescue cells when given simultaneously with 0.5 uM DDATHF. When folinic acid was given 24 h after DDATHF, a reversal of cytotoxicity was observed at 0.5 and 1 uM, but to a much lesser extent than simultaneous treatment.