Our data indicate that alpha-tocopherol used in an oral dose of 2 g/m2 daily results in a six- to eightfold increase of the vitamin E levels in serum. The occurrence of congestive heart failure in three patients and the observation of significant pathologic changes in endomyocardial biopsies in approximately half of the patients treated with a median cumulative adriamycin dose level of 550 mg/m2 indicate that alpha-tocopherol does not offer substantial protection against adriamycin-induced cardiac toxicity. The antitumor activity of the drug, however, is not compromised by the concomitant administration of the vitamin.

No abstract

In an effort to achieve high concentrations and prolonged exposure times, high-dose methotrexate (MTX) was administered by the intra-arterial route over 6 hours at a dose of 12.5 g/m2 to nine patients with osteosarcoma. This was followed by citrovorum factor (CF) rescue, which was initiated 12 hours after completion of the infusion (MTX-CF). The regimen achieved high local concentrations over a finite period. No toxicity was encountered. Treatment was administered at weekly intervals, during which intravenous MTX-CF was interposed if facilities for intra-arterial administration were not available. However, despite increases in local venous concentrations and exposure times, only four of nine patients (44%) responded. This is similar to responses achieved with 7.5 g/m2 (48%) with CF initiated 2 hours after completion of the infusion. Higher MTX doses, intra-arterial administration, and prolongation of cytotoxic exposure time did not confer a therapeutic advantage as opposed to "conventional" intravenous high doses.

No abstract