A Phase II Trial of Imatinib Mesylate in Merkel Cell Carcinoma (Neuroendocrine Carcinoma of the Skin)

Abstract

BACKGROUND Imatinib mesylate (Gleevec®) was evaluated as a treatment for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) based on the identification of strong c-KIT staining of these neoplasms. METHODS Eligibility included patients with measurable metastatic or unresectable MCC, c-KIT (CD117) expression and a Zubrod performance status of 0–2. Imatinib 400 mg daily was administered orally in 28-day cycles to 23 patients. RESULTS Overall, imatinib was well tolerated with Grade 1 or 2 nausea, diarrhea, and hematologic toxicity as the most frequent side effects. A partial response was seen in 1 patient (4%; 95% CI: 0% – 22%). Median progression-free survival was 1 month (95% CI: 1–2 months). Median overall survival was 5 months (95% CI 2–8 months). One patient achieved a partial response and another had prolonged disease stabilization while receiving treatment. CONCLUSIONS The majority of patients progressed rapidly within 1–2 cycles of treatment. The observed progression-free survival and overall survival were not adequate to conclude that this agent was active in advanced MCC, and thus the planned second stage of patient accrual was not opened.

Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors

“…It has been established that activating mutations in the KIT and platelet-derived growth factor receptor α genes are rare events in MCC, although miscellaneous alterations in those genes have been demonstrated [22,24]. Moreover, therapeutic trials of tyrosine kinase inhibitors in advanced MCC have yielded poor results [25]. Although c-kit expression does not appear to serve as a response marker for tyrosine kinase inhibition in MCC, its expression as part of the immunohistochemical profile of subsets of the tumor remains of interest.…”

Molecular characteristics and potential therapeutic targets in Merkel cell carcinoma

“…In this study, imatinib (400 mg) was administered daily, orally, in 28-day cycles to 23 patients. There was no significant decrease in progression-free or overall survival in advanced MCC 85 86…”

Functions and Uses of Immunohistochemical Stains in Cutaneous Infiltrates of Hematopoietic Origin: A Review for the Practicing Dermatologist

“…Unfortunately, patients rapidly progressed even with imatinib treatment, and the trial was closed. 106 Thus, CD117 expression does not necessarily indicate that the process will respond to treatments directed at this marker.…”