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Updated: Aug 8, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
A phase II, pharmacokinetic, and biologic study of semaxanib and thalidomide in patients with metastatic melanoma
Monica M Mita1, Eric K Rowinsky, Leonardo Forero
1Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78229, USA.
Purpose:
This phase II study evaluated the combination of semaxanib, a small molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor-2, and thalidomide in patients with metastatic melanoma to assess the efficacy, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the combination.
Patients And Methods:
Patients with metastatic melanoma, who had failed at least one prior biologic and/or chemotherapeutic regimen, were treated with escalating doses of thalidomide combined with a fixed dose of semaxanib.
Results:
Twelve patients were enrolled and received 44 courses of semaxanib at the fixed dose of 145 mg/m2 intravenously twice-weekly in combination with thalidomide, commencing at 200 mg daily with intrapatient dose escalation as tolerated. Treatment with semaxanib was initiated 1 day before thalidomide in the first course, permitting the assessment of the PKs of semaxanib alone (course 1) and in combination with thalidomide (course 2). The principal toxicities included deep venous thrombosis, headache, and lower extremity edema. Of ten patients evaluable for response, one complete response lasting 20 months and one partial response lasting 12 months were observed. Additionally, four patients had stable disease lasting from 2 to 10 months. The PKs of semaxanib were characterized by drug exposure parameters comparable to those observed in single-agent phase II studies, indicating the absence of major drug-drug interactions. Maximum semaximib plasma concentration values were 1.2-3.8 microg/ml in course 1 and 1.1-3.9 microg/ml in course 2. The mean terminal half-life was 1.3 ( +/- 0.31) h. Biological studies revealed increasing serum VEGF concentrations following treatment in patients remaining on study for more than 4 months.
Conclusion:
The combination of semaxanib and thalidomide was feasible and demonstrated anti-tumor activity in patients with metastatic melanoma who had failed prior therapy. Further evaluations of therapeutic strategies that target multiple angiogenesis pathways may be warranted in patients with advanced melanoma and other malignancies.
Insights
The combination of semaxanib and thalidomide showed anti-tumor activity in metastatic melanoma patients who failed prior treatments. This combination therapy is feasible and warrants further investigation for advanced melanoma.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic melanoma is a significant health concern with limited treatment options for patients who have failed prior therapies.
- Targeting angiogenesis, a key process in tumor growth and metastasis, is a promising therapeutic strategy.
Purpose of the Study:
- To evaluate the efficacy and tolerability of combining semaxanib (a VEGF receptor-2 inhibitor) with thalidomide in metastatic melanoma.
- To assess the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of this combination therapy.
Main Methods:
- A phase II study involving patients with metastatic melanoma who had prior treatment failure.
- Escalating doses of thalidomide were combined with a fixed dose of semaxanib (145 mg/m2 IV twice-weekly).
- PK/PD assessments were conducted, with semaxanib initiated before thalidomide in the first course.
Main Results:
- One complete response (20 months) and one partial response (12 months) were observed among 10 evaluable patients.
- Four patients achieved stable disease for 2-10 months.
- The combination was feasible, with toxicities including deep venous thrombosis, headache, and edema. Semaxanib PKs were comparable to single-agent studies, indicating no major drug-drug interactions.
Conclusions:
- The combination of semaxanib and thalidomide is a feasible treatment option demonstrating anti-tumor activity in pre-treated metastatic melanoma patients.
- Further research into multi-targeted angiogenesis therapies is recommended for advanced melanoma and other cancers.
