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A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Phase II trial of imatinib mesylate in patients with metastatic melanoma
1Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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.
Insights
Imatinib showed minimal efficacy for metastatic melanoma, but one patient with high c-kit expression had a significant response. Further investigation into imatinib for specific c-kit aberrations in melanoma is warranted.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic melanoma often expresses protein tyrosine kinases (PTKs) that are potential therapeutic targets.
- Imatinib is a targeted therapy known to inhibit certain PTKs.
Purpose of the Study:
- To evaluate the efficacy and tolerability of imatinib in patients with metastatic melanoma expressing specific PTKs.
- To identify potential predictive markers for imatinib response in melanoma.
Main Methods:
- A Phase II clinical trial involving 21 patients with metastatic melanoma.
- Patients received imatinib 400 mg twice daily.
- Tumor PTK expression (c-kit, PDGFR, c-abl, ABL) was assessed.
Main Results:
- One patient with acral lentiginous melanoma and high c-kit expression achieved a partial response lasting 12.8 months.
- The responder exhibited increased tumor and endothelial cell apoptosis.
- Imatinib was generally well-tolerated; fatigue and edema were the most common toxicities.
Conclusions:
- Imatinib demonstrated minimal clinical efficacy as a single agent for metastatic melanoma in this study.
- The significant response in one patient suggests potential activity in melanoma with specific c-kit aberrations.
- Further research is recommended to explore imatinib's role in a subset of melanoma patients with c-kit alterations.
