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Effect of Lonidamine on Systemic Therapy of DB-1 Human Melanoma Xenografts with Temozolomide
Kavindra Nath1, David S Nelson2, Jeffrey Roman2
1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, U.S.A. kavindra.nath@uphs.upenn.edu.
Background/Aim:
Since temozolomide (TMZ) is activated under alkaline conditions, we expected lonidamine (LND) to have no effect or perhaps diminish its activity, but initial results suggest it may actually enhance either or both short- and long-term activity of TMZ in melanoma xenografts.
Materials And Methods:
Cohorts of 5 mice with subcutaneous xenografts ~5 mm in diameter were treated with saline (control (CTRL)), LND only, TMZ only or LND followed by TMZ at t=40 min (time required for maximal tumor acidification).
Results:
Mean tumor volume for LND+TMZ for the period between 6 and 26 days was reduced compared to TMZ alone (repeated measures ANOVA F (1, 8), p=0.006), suggesting a pronounced impact of LND on this phenomenon. TMZ and LND+TMZ produced median growth delays of 82 and 106 days, respectively.
Conclusion:
The use of TMZ alone and in combination with LND deserves further investigation in treatment of melanoma and other malignancies.
