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What is the optimal dose and duration of treatment with etoposide? I. Maximum tolerated duration of daily treatment with 50, 75, and 100 mg of oral etoposide.

1992; National Institutes of Health; Volume: 19; Issue: 6 Suppl 14 Linguagem: Inglês

Splinter Ta, van der Gaast A, Kok Tc,

Cancer therapeutics and mechanisms

Because etoposide is a cell-cycle phase-specific drug, its degree of cytotoxicity likely relies on duration of cell exposure to a specific concentration. We investigated the maximum tolerated duration of oral etoposide treatment at doses of 100, 75, and 50 mg/d in previously treated patients with biopsy-proven, advanced cancer. "Maximum tolerated" was defined as tumor progression or hematologic toxicity (World Health Organization [WHO] grade > or = 2). The maximum tolerated duration in 19 patients given 100 mg/d was > or = 21 days, since this was the predetermined cutoff point; 3 patients discontinued etoposide because of early tumor progression, and 6 others had developed leukopenia or thrombocytopenia (WHO grade > 2) by day 21. The maximum tolerated duration in 13 patients given 75 mg/d was a median of 11 weeks (range, 2 to 19); 6 patients developed tumor progression and 6 others leukopenia (WHO grade > or = 2) requiring discontinuation of treatment. Ten patients given 50 mg/d tolerated therapy for a median of 13 weeks (range, 3 to 26 weeks); treatment was halted in seven patients because of tumor progression, two because of leukopenia (WHO grade > or = 2), and one because of stomatitis. The data from this study and others suggest that above a certain minimal plasma level, etoposide induces concentration-dependent cumulative toxicity. What remains to be determined is the minimal plasma level per tumor type. It will also be interesting to see whether myelopoiesis, thrombocytopoiesis, and erythropoiesis have differential sensitivity to etoposide, since thrombocytopenia did not occur using daily etoposide doses of 50 and 75 mg, whereas at the same doses 10 of 23 patients required erythrocyte transfusion.