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Response predictors to adjuvant therapy

Gogas, H.

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doi: 10.1097/01.cmr.0000382769.90816.58
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Interferon alfa (IFNα) was the first cytokine to demonstrate antitumor activity in patients with advanced melanoma and has been widely tested as adjuvant therapy of melanoma in patients with intermediate and higher risk for recurrence melanoma. In 1995, it was approved for adjuvant treatment of patients with stage IIB/III melanoma by the United States Food and Drug Administration (FDA). However, the tolerability of this regimen has been an issue due to the frequent occurrence of flu-like symptoms, fatigue, anorexia, and occasional depression.

Attempts to identify the subset of patients who benefit from adjuvant treatment with IFNα-2b have been undertaken but the results of these efforts have largely been disappointing to date. There are no clinical or demographic features of the patient population that is benefited by this therapy that can presently be used in the clinic to distinguish patients who are likely benefit HDI therapy from those patients who ultimately do not. There is a critical need for greater understanding of the immunological and disease-related variables that predict clinical benefit from IFNα-2b. The identification of predictive markers that permit selection of patients who are most likely to benefit would allow us to avoid the toxicity of treatment that is not associated with benefit, in more than half of patients who are now offered this therapy.

Subgroup analyses of the ECOG and EORTC adjuvant trials, translational research studies in tissue from the neoadjuvant high-dose interferon trial, corollary serum and DNA studies of E1690, E1694, E2696, EORTC 18952 and the Hellenic Cooperative Oncology Group have indentified cohorts of patients whom might be more responsive to adjuvant interferon.

In conclusion these findings should be further validated in prospective adjuvant trials and corroborated in larger patient samples.

© 2010 Lippincott Williams & Wilkins, Inc.