A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma.
Lomeguatrib, an O(6)-methylguanine-DNA methyltransferase inactivator, was evaluated in an extended dosing regimen with temozolomide, designed according to pharmacodynamic data from previous studies. Patients with unresectable stage 3 or 4 cutaneous or unknown primary melanoma metastases were treated with lomeguatrib 40 mg, b.i.d. for 10 or 14 days and temozolomide 75-100 mg m(-2) on days 1-5. Drugs were administered orally with cycles repeated every 28 days, for up to six cycles. A total of 32 patients were recruited to the study. Lomeguatrib for 10 days with temozolomide 75 mg m(-2) was established as the optimal extended lomeguatrib dosing schedule, with haematological toxicity being dose limiting. There were two partial responses to treatment giving an overall response rate of 6.25%. Extending lomeguatrib administration beyond that of temozolomide requires a reduced dose of the latter agent. Only limited clinical activity was seen, suggesting no advantage for this regimen over conventional temozolomide administration in the treatment of melanoma.
Kefford
R F
RF
Department of Medicine, Westmead Hospital, Westmead, New South Wales, Australia.
Thomas
N P B
NP
Corrie
P G
PG
Palmer
C
C
Abdi
E
E
Kotasek
D
D
Beith
J
J
Ranson
M
M
Mortimer
P
P
Watson
A J
AJ
Margison
G P
GP
Middleton
M R
MR
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000633:toxicity*; D002648:Child; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D018579:Patient Selection; D011687:Purines / Q000633:toxicity*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D011687:Purines; D003606:Dacarbazine; C521206:lomeguatrib; D000077204:Temozolomide