A randomised dose escalation study of subcutaneous interleukin 2 with and without levamisole in patients with metastatic renal cell carcinoma or malignant melanoma

Ahmed, FY; Leonard, GA; A’Hern, Roger; Taylor, A. E.; Lorentzos, A.; Atkinson, H.; Moore, J.; Nicolson, M. C.; Riches, P. G.; Gore, M.

doi:10.1038/bjc.1996.498

Cited by 13 publications

(4 citation statements)

References 16 publications

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“…Nevertheless, more recent studies have somehow questioned the efficacy of levamisole as an immunostimulant (e.g. : Toivanen et al 1981;Webster et al 1982;Aymard et al 1984;Schiller et al 1991;Ahmed et al 1996). Likewise, studies questioned the efficacy of levamisole in the treatment of rheumatoid arthritis (Dinai and Pras 1975) or skin infections (Chang and Fiumara 1978;Seidlin and Straus 1984;Sanchez 2000).…”

Section: Side Effects Of Tetramisole and Levamisole Therapiesmentioning

confidence: 93%

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Nowak

Rosay

Czégé

et al. 2015

Subcellular Biochemistry

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Tissue non-specific alkaline phosphatase (TNAP) may be involved in the synthesis of GABA and adenosine, which are the main inhibitory neurotransmitters in cortex. We explored this putative TNAP function through electrophysiological recording (local field potential ) in slices of mouse somatosensory cortex maintained in vitro. We used tetramisole, a well documented TNAP inhibitor, to block TNAP activity. We expected that inhibiting TNAP with tetramisole would lead to an increase of neuronal response amplitude, owing to a diminished availability of GABA and/or adenosine. Instead, we found that tetramisole reduced neuronal response amplitude in a dose-dependent manner. Tetramisole also decreased axonal conduction velocity. Levamisole had identical effects. Several control experiments demonstrated that these actions of tetramisole were independent from this compound acting on TNAP. In particular, tetramisole effects were not stereo-specific and they were not mimicked by another inhibitor of TNAP, MLS-0038949. The decrease of axonal conduction velocity and preliminary intracellular data suggest that tetramisole blocks voltage-dependent sodium channels. Our results imply that levamisole or tetramisole should not be used with the sole purpose of inhibiting TNAP in living excitable cells as it will also block all processes that are activity-dependent. Our data and a review of the literature indicate that tetramisole may have at least four different targets in the nervous system. We discuss these results with respect to the neurological side effects that were observed when levamisole and tetramisole were used for medical purposes, and that may recur nowadays due to the recent use of levamisole and tetramisole as cocaine adulterants.

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Section: Side Effects Of Tetramisole and Levamisole Therapiesmentioning

confidence: 93%

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Nowak

Rosay

Czégé

et al. 2015

Subcellular Biochemistry

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“…The fourth study, reported by Quirt et al [20], demonstrated a trend toward a disease-free and overall survival benefit of levamisole, although it was of borderline statistical significance. Levamisole has also been tested in combination with interleukin-2 in two randomized studies of patients with advanced melanoma, but no benefit was achieved [23,24]. No further investigations are planned for this agent.…”

Section: Levamisolementioning

confidence: 95%

Melanoma: Adjuvant therapy and other treatment options

Terando¹,

Sabel

Sondak³

2003

Curr. Treat. Options in Oncol.

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Melanoma, diagnosed and treated at its earliest stages, can be successfully cured by surgery alone. However, when metastatic beyond the regional nodes, it is almost uniformly deadly. Adjuvant therapy targeted toward the treatment of microscopic residual disease after surgical resection is the subject of intense scientific investigation because this is the stage at which it is possible to have the greatest impact on disease-free and overall survival. However, standard therapies commonly used for other solid tumors have had disappointing results in the treatment of melanoma in the adjuvant setting. These disappointing results have led researchers and clinicians to work to develop innovative treatment strategies for this disease, most of which center on the use of immunotherapy. The realm of cancer immunotherapy is broad and rapidly expanding; it encompasses strategies using immunomodulating agents, such as interferon and interleukin-2, in addition to a wide range of novel vaccination strategies for the induction of active antitumor immune responses. Although clinical trials continue to be conducted to sort out the safety and efficacy of a myriad of new treatment modalities and novel combinations of the old and the new, data indicate that high-dose interferon-alfa-2b should be offered to appropriately selected intermediate- and high-risk patients with melanoma not involved in an experimental protocol.

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“…The fourth study, by Quirt et al [78], did demonstrate a trend towards a disease-free and overall survival benefit of levamisole, although it was of borderline statistical significance. Levamisole has also been tested in combination with interleukin-2 in two randomized studies of patients with advanced melanoma, but no benefit was obtained [81,82]. No further investigations are planned for this agent.…”

Section: Immunostimulantsmentioning

confidence: 96%

Current state of treatment for primary cutaneous melanoma

Sabel

Sondak

2004

Clin Exp Med

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The incidence of malignant melanoma has been rising steadily for the last 30 years. Through physician and patient education, surveillance of high-risk individuals, and biopsy of any suspicious lesions, more lesions are being diagnosed earlier, where there is a high cure rate. Unfortunately many patients will still present with thicker lesions or nodal involvement, which carries a significantly worse prognosis. Over the past decade, there have been several changes in the management of primary cutaneous melanoma. These have stemmed from novel surgical approaches, a new understanding of melanoma biology, and randomized clinical trials designed to improve outcome and decrease the morbidity of therapy. This article will review the clinical evidence behind the current treatment recommendations for primary cutaneous melanoma as well as some of the emerging data on innovative immunologic-approaches to melanoma treatment.

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A randomised dose escalation study of subcutaneous interleukin 2 with and without levamisole in patients with metastatic renal cell carcinoma or malignant melanoma

Cited by 13 publications

References 16 publications

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Melanoma: Adjuvant therapy and other treatment options

Current state of treatment for primary cutaneous melanoma

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