Phase II trial of imatinib mesylate in patients with metastatic melanoma.
Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.
Kim
K B
KB
Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Eton
O
O
Davis
D W
DW
Frazier
M L
ML
McConkey
D J
DJ
Diwan
A H
AH
Papadopoulos
N E
NE
Bedikian
A Y
AY
Camacho
L H
LH
Ross
M I
MI
Cormier
J N
JN
Gershenwald
J E
JE
Lee
J E
JE
Mansfield
P F
PF
Billings
L A
LA
Ng
C S
CS
Charnsangavej
C
C
Bar-Eli
M
M
Johnson
M M
MM
Murgo
A J
AJ
Prieto
V G
VG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001483:Base Sequence; D001549:Benzamides; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate