Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma

Abstract

BACKGROUND. Although chemosensitivity to antiosteosarcoma agents is the most important prognostic factor in human osteosarcoma, none of the many chemosensitivity tests reported previously are reliable and clinically useful. In this study, the authors investigated the reliability and clinical availability of doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as a new chemosensitivity test for osteosarcoma. METHODS. Doxorubicin (adriamycin [ADM]) binding ability (%AB) to nuclear DNA in isolated osteosarcoma cells was assessed by ABA in 14 patients with primary osteosarcoma who were treated with preoperative chemotherapy containing ADM and 6 patients with relapsed osteosarcoma after intensive chemotherapy. Histologic responses to preoperative chemotherapy were evaluated by percentage of tumor necrosis (%necrosis). RESULTS. Four of the 14 patients with primary osteosarcoma had %AB > 80% (97.3 ± 3.7%) and demonstrated good histologic responses (>90% of %necrosis) to preoperative chemotherapy, whereas the remaining 10 patients had %AB < 80% (38.9 ± 21.0%) and demonstrated poor responses. Patients with recurrent osteosarcoma that was clinically evaluated to be resistant to previous chemotherapy also had low %AB (34.2 ± 28.3%). CONCLUSIONS. Because the results of the current study revealed that ABA is useful for predicting chemosensitivity to chemotherapy with ADM as well as chemotherapy without ADM for patients with osteosarcoma, and because ABA technically is simple and results can be assessed rapidly, the authors conclude that ABA is a clinically useful chemosensitivity test for patients with osteosarcoma.