Outpatient Intravenous Interleukin-2 with Famotidine Has Activity in Metastatic Melanoma

Quan, Walter; Quan, Francine M.; Perez, Mia; Johnson, Erin M.

doi:10.1089/cbr.2012.1239

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…Consequently, it is not surprising that IL2 is only successful therapeutically in a minority of patients, ie, some 7% or so. Moreover, some investigators have observed effective clinical responses using intermittent short bolus IL2 dosing, rather than longer IL2 infusions 2,17…”

Section: Resultsmentioning

confidence: 99%

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The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses

Coventry¹,

Ashdown²

2012

CMAR

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BackgroundThis year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma. IL2 therapy for cancer has stood the test of time, with continued widespread use in Europe, parts of Asia, and the US. Clinical complete responses are variably reported at 5%–20% for advanced malignant melanoma and renal cell carcinoma, with strong durable responses and sustained long-term 5–10-year survival being typical if complete responses are generated.MethodsThe literature was reviewed for the actions and clinical effects of IL2 on subsets of T cells. The influence of IL2 on clinical efficacy was also sought.ResultsThe review revealed that IL2 is capable of stimulating different populations of T cells in humans to induce either T effector or T regulatory responses. This apparent “functional paradox” has confounded a clear understanding of the mechanisms behind the clinical effects that are observed during and following administration of IL2 therapy. An average complete response rate of around 7% in small and large clinical trials using IL2 for advanced renal cell carcinoma and malignant melanoma has been shown from a recent review of the literature.ConclusionThis review considers the published literature concerning the actions and emerging clinical effects of IL2 therapy, spanning its 20-year period in clinical use. It further details some of the recently described “bimodal” effects of IL2 to explain the apparent functional paradox, and how IL2 might be harnessed to emerge rapidly as a much more effective and predictable clinical agent in the near future.

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Section: Resultsmentioning

confidence: 99%

“…Moreover, some investigators have observed effective clinical responses using intermittent short bolus IL2 dosing, rather than longer IL2 infusions. 2 , 17 …”

Section: Resultsmentioning

confidence: 99%

The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses

Coventry¹,

Ashdown²

2012

CMAR

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“…For example, high doses of IL-2 can be effective but are associated with greater toxicity. However, new data suggest that the addition of famotidine to IL-2 may decrease its toxicity as it enhances lymphokine-activated killer cell activity, whilst maintaining its activity against melanoma [ 58 ]. The CTL response is another example of the beneficial effects brought by the addition of new drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Regimens including carmustine, cisplatin, dacarbazine, tamoxifen or vinblastine, with or without IL-2 or IL-2 associated with IFN-α achieved a response rate ranging from 23 to 32.5%, with an OS rate of between 4.6 and 11.3 months [ 20 , 54 – 57 ]. Quan et al recently reported that famotidine may decrease IL-2 toxicity as it enhances lymphokine-activated killer cell activity, whilst maintaining activity against melanoma [ 58 ].…”

Section: Immunomodulatory Agentsmentioning

confidence: 99%

Metastatic melanoma – a review of current and future drugs

Velho¹

2012

DIC

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Background:Melanoma is one of the most aggressive cancers, and it is estimated that 76,250 men and women will be diagnosed with melanoma of the skin in the USA in 2012. Over the last few decades many drugs have been developed but only in 2011 have new drugs demonstrated an impact on survival in metastatic melanoma.Methods:A systematic search of literature was conducted, and studies providing data on the effectiveness of current and/or future drugs used in the treatment of metastatic melanoma were selected for review. This review discusses the advantages and limitations of these agents, evaluating past, current and future clinical trials designed to overcome such limitations.Results:To date, there are four drugs approved by the Food and Drug Administration for melanoma (dacarbazine, interleukin-2, ipilimumab and vemurafenib). Despite efforts to develop new drugs, few of them have demonstrated any clinical benefits. Approved in 1975, dacarbazine remains the gold standard in chemotherapy, although ipilimumab and vemurafenib have raised many hopes in the last few years. Combining dacarbazine or other chemotherapy agents with new pharmacological agents may be a new way to achieve better clinical responses in patients with metastatic melanoma.Discussion:Advances in the molecular knowledge of melanoma have led to major improvements in the treatment of patients with metastatic melanoma, providing new targets and insights. However, heterogeneity amongst study populations, different approaches to treatment and the different melanoma types and localisations included in the trials makes their comparison difficult. New studies focusing on drugs developed in recent decades are warranted.

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“…Notably, 10-year-survival rates have been high in patients who consisted these 7% (Atkins et al, 1999;Fisher et al, 2000;Klapper et al, 2008;Grivas and Redman, 2011;Prieto et al, 2012). Interestingly, certain studies have reported effective clinical responses using intermittent short bolus IL-2 dosing rather than longer IL-2 infusions (Grivas and Redman, 2011;Quan et al, 2012). In certain situations, either IL-2 and/or IL-2R can be released or expressed by cancer cells themselves Alileche et al, 1993;Coventry et al, 1996;Barbour and Coventry, 2003;Rangel-Corona et al, 2010).…”

Section: Interleukin-2 and Cancermentioning

confidence: 99%