Abstract: The use of tetrahydrofolate, methylene-tetrahydrofolate and/or methyl-tetrahydrofolate, and at least one multi-targeting antifolate, for the manufacture of a pharmaceutical composition for the treatment of cancer is disclosed. By combining the multi-targeting anti-folate with tetrahydrofolate, methylene-tetrahydrofolate and/or methyl-tetrahydrofolate, it is possible to remarkably reduce toxic side-effects without diminishing the anti-tumour action of the drugs. A pharmaceutical composition, a kit comprising the pharmaceutical composition as well as a method for the treatment of cancer are also disclosed.