Advanced ovarian cancer. Dose intensity.
BACKGROUND
The rationale for dose intensity is based on pre-clinical observations in experimental model systems of cancer as well as upon retrospective studies correlating the impact of dose intensity upon response rates and survival.


METHODS
A review has been performed based on trials attempting to compare the effects of two different dose intensities of either cisplatin or carboplatin, combinations of cisplatin and carboplatin, combined platinum with additional agents, and high-dose chemotherapy, regimens requiring hematologic support.


RESULTS
The early phase II trials suggested that there may be an important dose response range over clinically achievable platinum doses, but randomized trials have failed to consistently show a clinically significant improvement with high-dose therapy. Reasons for this may be differences in patient selection, that total dose is the most important factor, or that a more than two-fold increase in dose intensity is needed to detect differences in response and survival rates. Phase I and II studies indicate that high, but short lasting, response rates can be achieved with high-dose therapy with haematopoietic support in refractory patients, but the toxicity is substantial. Paclitaxel dose intensity is presently being studied in several trials.


CONCLUSIONS
Future trials of dose intensity should be focused upon patients with small volume disease and drug sensitive tumours.
Ozols
R F
RF
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
Thigpen
J T
JT
Dauplat
J
J
Colombo
N
N
Piccart
M J
MJ
Bertelsen
K
K
Levin
L
L
Lund
B
B
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D016190:Carboplatin / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000628:therapy; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
D016190:Carboplatin; D002945:Cisplatin