A Phase Ib/II trial of granulocyte-macrophage?colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastases

Hotton, Kirsten M.; Khorsand, Masoud; Hank, Jacquelyn A.; Albertini, Mark R.; Kim, Kyung Mann; Wilding, George; Salamat, M. Shahriar; Larson, Barbara A.; Sondel, Paul M.; Schiller, Joan H.

doi:10.1002/(sici)1097-0142(20000415)88:8<1892::aid-cncr19>3.0.co;2-2

Cited by 22 publications

(1 citation statement)

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“…Thus it appears that non-specific activation of the coagulation system, and a resulting potential for thrombosis, occur as a result of IL-2 treatment. Given the inherently pro-thrombotic state of many cancer patients, it is theoretically possible that IL-2 therapy may have thrombotic complications, which indeed have previously been reported [52]. …”

Section: Introductionmentioning

confidence: 97%

Intravenous ascorbic acid as an adjuvant to interleukin-2 immunotherapy

Wagner

Markosian²,

Ajili

et al. 2014

Journal of Translational Medicine

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Interleukin-2 (IL-2) therapy has been demonstrated to induce responses in 10-20% of advanced melanoma and renal cell carcinoma patients, which translates into durable remissions in up to half of the responsers. Unfortunately the use of IL-2 has been associated with severe toxicity and death. It has been previously observed and reported that IL-2 therapy causes a major drop in circulating levels of ascorbic acid (AA). The IL-2 induced toxicity shares many features with sepsis such as capillary leakage, systemic complement activation, and a relatively non-specific rise in inflammatory mediators such as TNF-alpha, C-reactive protein, and in advanced cases organ failure. Animal models and clinical studies have shown rapid depletion of AA in conditions of sepsis and amelioration associated with administration of AA (JTM 9:1-7, 2011). In contrast to other approaches to dealing with IL-2 toxicity, which may also interfere with therapeutic effects, AA possesses the added advantage of having direct antitumor activity through cytotoxic mechanisms and suppression of angiogenesis. Here we present a scientific rationale to support the assessment of intravenous AA as an adjuvant to decrease IL-2 mediated toxicity and possibly increase treatment efficacy.

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Section: Introductionmentioning

confidence: 97%