title: Phase II trial of imatinib mesylate in patients with metastatic melanoma.
abstract: 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.
authors: Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: K B
authors: KB
authors: Kim
authors: O
authors: O
authors: Eton
authors: D W
authors: DW
authors: Davis
authors: M L
authors: ML
authors: Frazier
authors: D J
authors: DJ
authors: McConkey
authors: A H
authors: AH
authors: Diwan
authors: N E
authors: NE
authors: Papadopoulos
authors: A Y
authors: AY
authors: Bedikian
authors: L H
authors: LH
authors: Camacho
authors: M I
authors: MI
authors: Ross
authors: J N
authors: JN
authors: Cormier
authors: J E
authors: JE
authors: Gershenwald
authors: J E
authors: JE
authors: Lee
authors: P F
authors: PF
authors: Mansfield
authors: L A
authors: LA
authors: Billings
authors: C S
authors: CS
authors: Ng
authors: C
authors: C
authors: Charnsangavej
authors: M
authors: M
authors: Bar-Eli
authors: M M
authors: MM
authors: Johnson
authors: A J
authors: AJ
authors: Murgo
authors: V G
authors: VG
authors: Prieto
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate