Effectiveness and Tolerability of Low-Dose Cyclophosphamide and Low-Dose Intravenous Interleukin-2 Disseminated Melanoma

Mitchell, Malcolm S.; Kempf, Raymond A.; Harel, William; Shau, Hungyi; Boswell, William D.; Lind, Susan; Bradley, Edward C.

doi:10.1200/jco.1988.6.6.1067

Cited by 20 publications

(25 citation statements)

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“…Despite extensive attempts to assess parameters in the peripheral blood that can predict the outcome of this treatment, only the rebound lymphocytosis after cessation the IL-2 infusion [22] and the lymphokineOffprint requests to: G. G. Hermann activated killer (LAK) cell cytotoxicity induced by IL-2 in vivo [15,17] have been found to relate to the clinical response. The present study was carried out to determine predictors of the clinical effect of IL-2 therapy in metastatic renal cell cancer by measuring a higher number of immunological blood parameters at shorter intervals during IL-2 therapy than investigated in previous studies.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma

et al. 1991

Cancer Immunol Immunother

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The purpose of this study was to determine immunological parameters in the peripheral blood that correlate with the clinical effect of interleukin-2 (IL-2) in patients with metastatic renal cell cancer. A group of 26 patients with metastatic renal cell cancer underwent IL-2 treatment using a 36-day schedule with continuous intravenous IL-2 infusion (3 x 10(6) units m-2 day-1) administered from days 1 to 5 and days 12 to 16. The white blood cell count and the absolute and relative number of neutrophils, lymphocytes, eosinophils and monocytes were recorded six times in peripheral blood during the treatment. Also the blood counts of T cell and NK cell subsets and cells expressing the T cell activation markers IL-2R alpha and VLA-1 were measured. The lymphokine-activated killer (LAK) cell cytotoxicity was measured either with or without additional in vitro stimulation by IL-2. Multivariate statistical analysis showed that the clinical responses were related to the administered dose of IL-2, to a low number of blood cells expressing IL-2 receptors and to a reduction in the blood monocyte count (P less than 0.05).

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Section: Introductionmentioning

confidence: 99%

Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma

et al. 1991

Cancer Immunol Immunother

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“…(Gemlo et al, 1988;von Rohr et al, 1993). While it is recognised that NK-and LAK-cell activities correlate with tumour responses in animal studies, this is less well established in man (Mitchell et al, 1988). LAK-cell activity, in vivo, has been found to be suboptimal in patients with advanced colorectal cancer receiving continuous infusions of rIL-2 .…”

Section: Pge2 During Ril-2 Infusionmentioning

confidence: 99%

In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses

Deehan

Heys²,

Simpson³

et al. 1994

Br J Cancer

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Recombinant interleukin 2 (rIL-2), when given to patients with advanced malignant disease, induces a limited beneficial effect, with only 20-30% of patients with solid tumours responding. This present study has identified those patients with advanced colorectal cancer most likely to respond to rIL-2 therapy, by analysis of serum cytokine levels, prior to and during rIL-2 treatment, documented in responders and non-responders. Responders were found to have significantly lower pretreatment serum IL-6 and soluble IL-2 receptor levels (sIL-2R) than non-responders (P < 0.01 and P < 0.05 respectively). During rIL-2 infusion, responders developed high circulating levels of IL-6 and had low constant levels of prostaglandin E2 (PGE2). Non-responders failed to produce IL-6 and demonstrated elevated serum concentrations of PGE2, during infusions of rIL-2. Thus, an enhanced ongoing IL-6 and sIL-2R response, prior to therapy, was detrimental to subsequent treatment with rIL-2. Differential production and/or release of cytokines and prostaglandins, during therapy, further determined the likelihood of response to rIL-2.

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“…However, some authors have demonstrated a direct correlation between a clinical response and increased non-MHC-restricted lytic activity, as observed in IL-2-treated patients with cancer of the head and neck 29 and in IL-2-treated patients after chemotherapy. 30 Conversely, other investigators found no significant correlation at all. 31 One reason for the difference in the results obtained by these groups may be the timing of the blood collections.…”

Section: Discussionmentioning

confidence: 61%

Increased non-major histocompatibility complex-restricted lytic activity in melanoma patients vaccinated with cytokine gene-transfected autologous tumor cells

Möller

Sun

et al. 2000

Cancer Gene Ther

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Genetically modified antitumoral vaccines focus on eliciting or increasing the T-cell-mediated antitumoral response. Little is known about non-major histocompatibility complex-restricted responses. In two phase I studies, we have immunized advanced melanoma patients with either interleukin-7 (IL-7) gene-transfected or IL-12 gene-transfected, autologous, irradiated melanoma cells. To monitor the immune response, peripheral blood mononuclear cells were collected before the first vaccination and 2 weeks after the third vaccination. Spontaneous lytic activity and lymphokine-activated killer (LAK) activity after a 5-day culture in the presence of 1000 U/mL IL-2 against autologous and against allogeneic melanoma cells were measured. In parallel, a precursor cytotoxic T-cell frequency analysis was performed using a 25-day limiting dilution analysis assay. A total of 10 of 14 immunologically evaluable patients demonstrated a marked increase in LAK activity, and 7 of 14 showed increased spontaneous lytic activities against autologous melanoma cells after three vaccinations. Remarkably, two patients with a good clinical performance status (Karnofsky index of Ͼ70; Multitest Merieux of Ͼ13.4 mm/3) and the highest cytotoxic T-lymphocyte (CTL) response after vaccination showed the only clear decrease in LAK and spontaneous lytic activity. Otherwise, three patients with no detectable CTL response after vaccination demonstrated an increase in LAK activity and the strongest increase in the autologous spontaneous lytic activity. This group of patients was associated with a poor clinical performance status (Karnofsky index of Ͻ70; Multitest Merieux of Ͻ4 mm/1) and with no clinical response. In conclusion, in accordance with other studies, a good clinical and immunological performance status appears to be the prerequisite for a successful CTL response. However, even strong non-major histocompatibility complex-restricted responses could be generated in patients with reduced clinical performance in vaccination therapies with gene-transfected autologous tumor cells. Cancer Gene Therapy (2000) 7, 976 -984

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Effectiveness and Tolerability of Low-Dose Cyclophosphamide and Low-Dose Intravenous Interleukin-2 Disseminated Melanoma

Abstract: The title of the article by Mitchell et al published in the March 1988 issue (6:409–424) should have read "Effectiveness and Tolerability of Low-Dose Cyclophosphamide and Low-Dose Intravenous Interleukin-2 in Disseminated Melanoma." The word "in" was erroneously left out.

Cited by 20 publications

References 0 publications

Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma

Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma

In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses

Increased non-major histocompatibility complex-restricted lytic activity in melanoma patients vaccinated with cytokine gene-transfected autologous tumor cells

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