CORRELATION BETWEEN HPLC-DETERMINED LONIDAMINE SERUM LEVELS AND CLINICAL-RESPONSE IN PATIENTS WITH ADVANCED OVARIAN-CANCER

Londiamine is an energolytic derivative of indazolcarboxilic acid whic h has been demonstrated to enhance cisplatin activity in ovarian cance r cell lines either sensitive or resistent to this drug, thus suggesti ng the potential reverting activity of the mechanisms of drug resistan ce. A study was performed on nine patients with advanced ovarian cance r treated with londiamine (LND) plus cisplatin (CDDP) as salvage thera py after the failure of first-line platinum containing chemotherapy. S erum LND was determined with a high-performance liquid chromatography (HPLC) method. The objective clinical response included one complete a nd three partial responses (overall response 44%). High LND serum leve ls were observed in three of four responding patients. the serum LND c oncentrations for theses patients, detected one hour after the first a nd second dose administrations, were 15.2 +/- 1.1 and 14.6 +/- 1.4 mu g/ml, respectively. Toxicity was mild to moderate, except for myalgia. The high serum levels of lonidamine detected in three of four respond ing patients suggests that the syngerism between LND and CDDP observed ovarian cancer cell lines may be confirmed in clinical practice. Howe ver, the potential role of LND in enhancing CDDP activity can be defin itely established in large randomized trials.