Advanced ovarian cancer. Drug resistance, supportive care and dose intensity.
BACKGROUND
Both intrinsic and acquired drug resistance occur in ovarian cancer. Much work on in vivo or in vitro, obtained drug resistance has been done and this knowledge is presently being converted into clinical studies.


METHODS
The review focuses on the detoxifying system, MDR (multidrug resistance), and supportive care in relation to dose intensity.


RESULTS
In vitro models suggest that the amount of glutathione, glutathione S-transferase activity or metallothioneins could play a role in the outcome of chemotherapy treatment. The results of human tumour samples studies however do not support this idea. Expression of the cell membrane P-glycoprotein in tumour cells appears 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 cisplatin induced nephrotoxicity, but the exact role of sulphur compounds in ameliorating the neurotoxicity is not yet established. The neuropeptide Org 2766 may be a possible neuroprotector. Hemopoietic growth factors such as GM-CSF, G-CSF and interleukin-3, protect the bone marrow to varying degrees. Autologous bone marrow transplantation induces high, but often short lasting response rates in chemotherapy resistant patients.


CONCLUSIONS
More clinical studies on intervention of drug resistance and on high dose chemotherapy are needed to define the role of these strategies in ovarian cancer.
de Vries
E G
EG
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Hamilton
T C
TC
Lind
M
M
Dauplat
J
J
Neijt
J P
JP
Ozols
R F
RF
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006801:Humans; D008658:Inactivation, Metabolic; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012189:Retrospective Studies
D000970:Antineoplastic Agents