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.
Department of Medicine, Westmead Hospital, Westmead, New South Wales, Australia.
R F
RF
Kefford
N P B
NP
Thomas
P G
PG
Corrie
C
C
Palmer
E
E
Abdi
D
D
Kotasek
J
J
Beith
M
M
Ranson
P
P
Mortimer
A J
AJ
Watson
G P
GP
Margison
M R
MR
Middleton
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