Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma

Abstract

BACKGROUND:Patients with mucosal and acral melanomas have limited treatment options and a poor prognosis. Mutations of the KIT oncogene in these melanoma subtypes provide a potential therapeutic target. METHODS: A multicenter phase 2 trial of sunitinib was conducted in patients with unresectable stage III or IV melanoma of a mucosal or acral primary origin. Patients were treated in 2 cohorts: cohort A received sunitinib at a dose of 50 mg daily for 4 weeks of a 6-week cycle, and cohort B received sunitinib at a dose of 37.5 mg daily on a continuous basis. Dose reductions were permitted for treatment-related toxicities, and tumor assessments were performed every 2 months. RESULTS: Fifty-two patients were enrolled: 21 in cohort A and 31 in cohort B. Four patients had confirmed partial responses, which lasted 5 to 10 months (1 with a KIT mutation). In both cohorts, the proportion of patients alive and progression-free at 2 months was 52% (95% confidence interval, 38%-66%); this was significantly larger than the hypothesized null of 5%. There was no significant difference in response or overall survival between the 25% of patients with a KIT mutation and those without one (response rate, 7.7% vs 9.7%; overall survival, 6.4 vs 8.6 months). The overall disease control rate was 44%, and a high rate of toxicity was associated with the treatment. CONCLUSIONS: Sunitinib showed activity in the treatment of mucosal and acral melanoma that was not dependent on the presence of a KIT mutation. However, the medication was poorly tolerated, and there were no prolonged responses. Cancer 2015;121:4007-15.

Improving the Diagnosis and Treatment of Acral Melanocytic Lesions

“…Additionally, a Phase II trial of sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, was performed in patients with stage III or IV metastatic AM. Although the medication was poorly tolerated, sunitinib Improving the diagnosis & treatment of acral melanocytic lesions REVIEW future science group www.futuremedicine.com showed short-term activity in the treatment of AM that was not dependent on the presence of KIT mutations [82].…”

Antitumor Activity of a Novel Tyrosine Kinase Inhibitor AIU2001 Due to Abrogation of the DNA Damage Repair in Non-Small Cell Lung Cancer Cells

“…Multi-kinase inhibitors targeting mainly FLT3 are generally accepted for acute myeloid leukemia (AML) treatment but are not clinically used on solid tumors due to low efficacy. Currently, combination treatments, instead of single therapeutic agents, are being extensively investigated for the treatment of solid tumors [9,10,11,12,13].…”

Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma

“…for treating advanced renal cell carcinoma, imatinib-resistant, or intolerant gastrointestinal stroma tumor (GIST), and advanced pancreatic neuroendocrine tumors [ 1 ]. Recent studies have reported that sunitinib controls c-KIT or non c-KIT mutated malignant melanoma (MM) [ 2 – 6 ]. However, sunitinib is not clinically widely used on solid tumors due to the low efficacy [ 6 – 9 ].…”

“…Recent studies have reported that sunitinib controls c-KIT or non c-KIT mutated malignant melanoma (MM) [ 2 – 6 ]. However, sunitinib is not clinically widely used on solid tumors due to the low efficacy [ 6 – 9 ]. How to improve the efficacy of sunitinib in solid tumor remains a big challenge for oncologists’ world widely.…”