Correlation between HPLC-determined lonidamine serum levels and clinical response in patients with advanced ovarian cancer.
Lonidamine is an energolytic derivative of indazolcarboxilic acid which has been demonstrated to enhance cisplatin activity in ovarian cancer cell lines either sensitive or resistant to this drug, thus suggesting the potential reverting activity of the mechanisms of drug resistance. A study was performed on nine patients with advanced ovarian cancer treated with lonidamine (LND) plus cisplatin (CDDP) as salvage therapy after the failure of first-line platinum containing chemotherapy. Serum LND was determined with a high-performance liquid chromatography (HPLC) method. The objective clinical response included one complete and three partial responses (overall response 44%). High LND serum levels were observed in three of four responding patients. The serum LND concentrations for these patients, detected one hour after the first and second dose administrations, were 15.2 +/- 1.1 and 14.6 +/- 1.4 micrograms/ml, respectively. Toxicity was mild to moderate, except for myalgia. The high serum levels of lonidamine detected in three of four responding patients suggests that the syngerism between LND and CDDP observed ovarian cancer cell lines may be confirmed in clinical practice. However, the potential role of LND in enhancing CDDP activity can be definitely established in large randomized trials.
Bottalico
C
C
Laboratory of Analysis, Oncology Institute of Bari, Italy.
Lorusso
V
V
Brandi
M
M
Micelli
G
G
Rella
C A
CA
Coviello
M
M
Atlante
A M
AM
Quaranta
M
M
De Lena
M
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D007191:Indazoles; D002945:Cisplatin; C016371:lonidamine