Subcutaneous Ril-2 in Advanced Melanoma and Kidney Carcinoma

Delena, M; Guida, Michele; Casamassima, A.; Addabbo, L; Abbate, I.; Correale, M.; Musci,; Lorusso,; Latorre, Agnese; Mastria, A

doi:10.3892/ijo.1.2.181

Cited by 3 publications

(2 citation statements)

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“…This increase was more evident in Group A and was limited to the first months of treatment; successively, behavior was similar in the two patient groups. CD 16 Natural Killer cells and CD25 cells expressing IL-2 receptor showed the most significant variations in comparison to their basal values and high levels persisted until the end of therapy. In particular, high levels of CD 16 were noted from the start of IL-2 maintenance therapy as effect of the primary chemotherapy treatment (triple values in Group A and double values in Group with respect to basal values) and this lymphocyte subset showed an ulterior slight increase at the end of treatment.…”

Section: Haemato-immunological Modificationsmentioning

confidence: 86%

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Long-term Subcutaneous Recombinant Interleukin-2 as Maintenance Therapy: Biological Effects and Clinical Implications

Guida¹,

Abbate²,

Casamassima³

et al. 1995

Cancer Biotherapy

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Several trials have evaluated the therapeutic efficacy of rIL-2 combined with more traditional treatments such as chemotherapy and radiotherapy, but the use of IL-2 as adjuvant therapy for minimal residual disease or to maintain clinical response obtained with other standard treatments has yet to be investigated. The aim of the present trial was to study the biological effects of maintenance long-term treatment (6 months) with subcutaneous low-dose IL-2 in 16 patients with different neoplasms previously treated with chemo-immuno therapeutic regimens or with surgery (7 metastatic renal cancers, 5 locally advanced renal cancers previously subjected to radical nephrectomy, 2 metastatic breast cancers, 1 small cell lung cancer, and 1 metastatic melanoma). Clinical tolerability, feasibility and therapeutic implications are also discussed. The IL-2 schedule was as follows: 4.5 million IU/day, 3 times weekly for 6 months. A total of 14 patients completed therapy without requiring dose modifications and are free of progression after a median duration of 8+ months (range: 7+ to 34+) while two patients progressed during therapy (one inflammatory breast cancer and one renal cancer). Important and persistent hemato-immunostimulating effects in both soluble (IL-2, sIL-2R, IL-6) and cellular (lymphocyte subsets, monocytes, eosinophils) parameters were noted during the entire treatment. The IL-2 related toxicity was quite low. Moreover, this long-term IL-2 therapy could control neoplastic growth and thus prolong clinical response obtained with standard treatments. Prospective randomized studies regarding the clinical efficacy have been initiated.

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Section: Haemato-immunological Modificationsmentioning

confidence: 86%

“…Behaviour ofT-lymphocyte subsets (CD4, CD8, T4/T8,CD 16, CD25, CD71) before treatment (basal values), after primary therapy (Time 0), and during 6 month rrL-2 maintenance therapy. The patients were separated into two groups: patients pretreated with IL-2 alone (Group A) and those pretreated with other therapeutical approaches (Group B).…”

mentioning

confidence: 99%

Long-term Subcutaneous Recombinant Interleukin-2 as Maintenance Therapy: Biological Effects and Clinical Implications

Guida¹,

Abbate²,

Casamassima³

et al. 1995

Cancer Biotherapy

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A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy

Elias

Hunt²

2001

Oncology

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Objective: To characterize prognostic factors for response of advanced renal cell carcinoma to interleukin-2-based regimens. Patients and Methods: Data compiled from 80 published series were examined for associations between patient characteristics and outcomes. Results: Response rates were highest in trials utilizing interleukin-2 combinations. Longer median survivals were associated with high percentages of patients with nephrectomy, good performance status, with publication year, response rates, and inversely with median ages. Associations of performance status and prior nephrectomy with response rates were detected in trials with individual patient details. The response rate was higher for patients older than the median age of patients entering each trial, and also higher for males. Among responders, attainment of complete response was associated with fewer sites of involvement. Pooled response duration of patients reported to have complete responses exhibited durability, but no correlation with prognostic factors. Selection factors may have influenced apparent differences between types of regimens. We confirm the potential for durable remissions from interleukin-2-based regimens.

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Interleukin-2

Whittington¹,

Faulds²

1993

Drugs

161

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Recombinant interleukin-2 (IL-2) products (e.g. aldesleukin, teceleukin) are nonglycosylated, modified forms of the endogenous compound. IL-2 acts as a pleiotropic mediator within the immune system, having a variety of effects via specific cell surface receptors. The interaction of IL-2 with the IL-2 receptor induces proliferation and differentiation of a number of T lymphocyte subsets, and stimulates a cytokine cascade that includes various interleukins, interferons and tumour necrosis factors. Antitumour effects of IL-2 appear to be mediated by its effects on natural killer, lymphokine-activated killer (LAK) and other cytotoxic cells. In vivo and in vitro effects of IL-2 seem to be dependent to a large extent on the environment; many studies have reported conflicting results, perhaps due to diverse populations of effector cells, the availability of other cytokines that have synergistic or inhibitory influences, and the dosage regimens used. The recombinant products appear to be biologically indistinguishable from native IL-2 in vitro and in vivo; the former induce minor antibody formation but this does not appear to alter functional properties. In patients with metastatic renal cell carcinoma, IL-2 therapy achieves average objective response rates of 20% (range 0 to 40%), with a complete response rate of about 5% (range 0 to 19%). Response duration varies considerably but can be durable (lasting for > 12 months), with some patients remaining in complete response for > 60 months. It is unclear at present whether higher dosage regimens improve clinical response, or whether combination therapy with other agents and/or adoptive therapy is beneficial. Survival duration may depend on the risk factors present, with poorer performance status and more than one site of metastases associated with shorter survival times. Patients with metastatic malignant melanoma receiving IL-2 as monotherapy show an average objective response rate of 13% (range 3 to 24%); however, objective response rate averages 30% (range 4 to 59%) when IL-2 is used in combination with other agents. Overall median survival appears to be about 10 months. Preliminary data indicate that IL-2 produces a lower response rate in patients with refractory colorectal carcinoma, ovarian cancer, bladder cancer, acute myeloid leukemia or non-Hodgkin's lymphoma. Adverse effects accompanying high dose, intravenous IL-2 therapy can be severe, with cardiovascular, pulmonary, haematological, hepatic, neurological, endocrine, renal and/or dermatological complications frequently requiring doses to be withheld.(ABSTRACT TRUNCATED AT 400 WORDS)

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Subcutaneous Ril-2 in Advanced Melanoma and Kidney Carcinoma

Cited by 3 publications

References 0 publications

Long-term Subcutaneous Recombinant Interleukin-2 as Maintenance Therapy: Biological Effects and Clinical Implications

Long-term Subcutaneous Recombinant Interleukin-2 as Maintenance Therapy: Biological Effects and Clinical Implications

A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy

Interleukin-2

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