Abstract
We have given marrow (BM) - ablative doses of PAM followed by BM autografting to children with neuroblastoma (NBL), Ewing's sarcoma (ES) and osteosarcoma (OS). To examine in vitro effects of this drug, we exposed fresh and cultured NBL (6 pts), ES (4), OS (5) and normal BM (9) cell colonies (CPU) to PAM in concentrations (cone) from 10−1 to 10−7 molar in a 14 day clonigenic assay. The T/2 of PAM measured by high pressure liquid chromatography was about 45 minutes. All CFU showed linear responses to PAM, correlating with both increasing drug cone and exposure duration (up to 8 hours). Fresh cells were significantly more sensitive than cultured cells. NBL-CFU were most sensitive, followed by OS, BM and ES in decreasing order. Repeat dosing up to 4 doses of PAM further inhibited CFU formation. We conclude: (1) NBL and OS CPU are more sensitive to PAM than normal BM or ES CFU; (2) PAM breakdown products apparently remain cytotoxic to tumor cells; (3) prolonged or repeated exposure may increase in vivo efficacy of PAM. We are currently correlating in vitro and in vivo cone of the parent drug and its metabolites with their cytotoxic effects.
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Graham-Pole, J., Worthington-White, D. & Riley, C. STUDIES WITH MELPHALAN (PAM) IN PEDIATRIC CANCER CELLS. Pediatr Res 18 (Suppl 4), 241 (1984). https://doi.org/10.1203/00006450-198404001-00886
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DOI: https://doi.org/10.1203/00006450-198404001-00886