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Review
. 2012 Nov;8(11):1401-6.
doi: 10.2217/fon.12.126.

Personalized therapy for metastatic melanoma: could timing be everything?

Roxana S Dronca  1 , Alexey A Leontovich, Wendy K Nevala, Svetomir N Markovic
Affiliations
Review

Personalized therapy for metastatic melanoma: could timing be everything?

Roxana S Dronca et al. Future Oncol. 2012 Nov.

Abstract

There is ample evidence that immune-related processes in humans are under temporal regulation. The circadian variation of humoral and cellular immunity is well documented and appears to be hormonally modulated via the hypothalamic-pituitary-adrenal axis. In advanced melanoma, it has recently been demonstrated that systemic immunity is repolarized toward a global state of chronic inflammation (Th2 dominance) and appears to be governed by infradian biorhythms of cytokines and immune cell subsets, which extend beyond the 24-h circadian variability reported in healthy volunteers. It is suggested that synchronizing administration of lymphodepleting chemotherapy (temozolomide) with these endogenous (individualized) immune dynamics (biorhythms) in patients with advanced/metastatic melanoma improves clinical outcomes compared with temozolomide used in a conventional 'random delivery' fashion.

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Figures

Figure 1
Figure 1
Example of infradian biorhythms of selected cytokines (A) and immune cells (B) in a patient with metastatic melanoma.
Figure 2
Figure 2. Clustering of immunological profiles for prediction of optimal time of chemotherapy delivery in a patient with metastatic melanoma
Bottom panel shows extrapolated relative concentration of selected cytokines; red line shows the summary biorhythm resulting from clustering of immune variables.
See this image and copyright information in PMC

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Website

    1. Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery. http://clinicaltrials.gov/ct2/show/NCT01328535?term=melanoma+and+temozol....

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