A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer.
Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity. In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24+ months) and three (11%) a minor response. Two patients have stable disease (greater than 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required. Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity. Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.
Mansi
J L
JL
Breast Unit, Royal Marsden Hospital, Sutton, Surrey.
de Graeff
A
A
Newell
D R
DR
Glaholm
J
J
Button
D
D
Leach
M O
MO
Payne
G
G
Smith
I E
IE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007191:Indazoles / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008593:Menopause; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011960:Receptors, Estrogen / Q000032:analysis
D000970:Antineoplastic Agents; D007191:Indazoles; D011960:Receptors, Estrogen; D000255:Adenosine Triphosphate; C016371:lonidamine