DRUG-RESISTANCE, SUPPORTIVE CARE AND DOSE INTENSITY

Background: Both intrinsic and acquired drug resistance occur in ovari an cancer. Much work on in vivo or in vitro, obtained drug resistance has been done and this knowledge is presently being converted into cli nical studies. Materials and methods: The review focuses on the detoxi fying system, MDR (multidrug resistance), and supportive care in relat ion to dose intensity. Results: In vitro models suggest that the amoun t of glutathione, glutathione S-transferase activity or metallothionei ns could play a role in the outcome of chemotherapy treatment. The res ults of human tumour samples studies however do not support this idea. Expression of the cell membrane P-glycoprotein in tumour cells appear s in vitro to be an important adverse prognostic factor concerning the effect of natural products. Again the results in human tumour samples vary. The supportive agent sodium thiosulphate protects against cispl atin induced nephrotoxicity, but the exact role of sulphur compounds i n ameliorating the neurotoxicity is not yet established. The neuropept ide Org 2766 may be a possible neuro- protector. Hemopoietic growth fa ctors such as GM-CSF, G-CSF and interleukin-3, protect the bone marrow to varying degrees. Autologous bone marrow transplantation induces hi gh, but often short lasting response rates in chemotherapy resistant p atients. Conclusions: More clinical studies on intervention of drug re sistance and on high dose chemotherapy are needed to define the role o f these strategies in ovarian cancer.