Abstract
Context: To date no efficacious treatments are available for advanced medullary thyroid carcinoma (MTC). Objective: We investigated in vitro and in vivo a new strategy for the therapy of MTC, combining human recombinant IL-2 with lanreotide (LAN), a somatostatin analog. Methods: The in vitro effects of LAN on the sensitivity of TT cells, a MTC cell line, to IL-2-stimulated human peripheral blood mononuclear cells were determined by a lactate dehydrogenase release assay. In addition, we evaluated the toxicity, the effects on quality of life, and the antitumor activity of sc low-dose IL-2 in combination with LAN (90 mg every 28 days) in a series of 6 patients with symptomatic and advanced MTC. Results: The cytotoxicity of IL-2-activated peripheral blood mononuclear cells was significantly increased in TT cells treated with LAN or LAN plus IL-2 compared with that in TT cells without treatment. The therapy was well tolerated, and a statistically significant improvement of quality of life was observed in patients treated with the combination of LAN and IL-2. After 6 months of therapy, partial response and stable disease have been recorded in 2 and 3 patients, respectively, with a significant decrease in calcitonin levels in 3 patients. Conclusions: Both in vitro and in vivo evidence suggests that the combination of LAN and IL-2 may have a role in the management of advanced and symptomatic MTC. However, these preliminary data require further validation in larger randomized trials.
| Original language | English |
|---|---|
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 98 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2013 |
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ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Endocrinology
- Biochemistry, medical
- Endocrinology, Diabetes and Metabolism
Cite this
Interleukin-2 and lanreotide in the treatment of medullary thyroid cancer : In vitro and in vivo studies. / Vitale, Giovanni; Lupoli, Giovanni; Guarrasi, Rosario; Colao, Annamaria; Dicitore, Alessandra; Gaudenzi, Germano; Misso, Gabriella; Castellano, Maria; Addeo, Raffaele; Facchini, Gaetano; Del Prete, Salvatore; Caraglia, Michele.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 10, 10.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-2 and lanreotide in the treatment of medullary thyroid cancer
T2 - In vitro and in vivo studies
AU - Vitale, Giovanni
AU - Lupoli, Giovanni
AU - Guarrasi, Rosario
AU - Colao, Annamaria
AU - Dicitore, Alessandra
AU - Gaudenzi, Germano
AU - Misso, Gabriella
AU - Castellano, Maria
AU - Addeo, Raffaele
AU - Facchini, Gaetano
AU - Del Prete, Salvatore
AU - Caraglia, Michele
PY - 2013/10
Y1 - 2013/10
N2 - Context: To date no efficacious treatments are available for advanced medullary thyroid carcinoma (MTC). Objective: We investigated in vitro and in vivo a new strategy for the therapy of MTC, combining human recombinant IL-2 with lanreotide (LAN), a somatostatin analog. Methods: The in vitro effects of LAN on the sensitivity of TT cells, a MTC cell line, to IL-2-stimulated human peripheral blood mononuclear cells were determined by a lactate dehydrogenase release assay. In addition, we evaluated the toxicity, the effects on quality of life, and the antitumor activity of sc low-dose IL-2 in combination with LAN (90 mg every 28 days) in a series of 6 patients with symptomatic and advanced MTC. Results: The cytotoxicity of IL-2-activated peripheral blood mononuclear cells was significantly increased in TT cells treated with LAN or LAN plus IL-2 compared with that in TT cells without treatment. The therapy was well tolerated, and a statistically significant improvement of quality of life was observed in patients treated with the combination of LAN and IL-2. After 6 months of therapy, partial response and stable disease have been recorded in 2 and 3 patients, respectively, with a significant decrease in calcitonin levels in 3 patients. Conclusions: Both in vitro and in vivo evidence suggests that the combination of LAN and IL-2 may have a role in the management of advanced and symptomatic MTC. However, these preliminary data require further validation in larger randomized trials.
AB - Context: To date no efficacious treatments are available for advanced medullary thyroid carcinoma (MTC). Objective: We investigated in vitro and in vivo a new strategy for the therapy of MTC, combining human recombinant IL-2 with lanreotide (LAN), a somatostatin analog. Methods: The in vitro effects of LAN on the sensitivity of TT cells, a MTC cell line, to IL-2-stimulated human peripheral blood mononuclear cells were determined by a lactate dehydrogenase release assay. In addition, we evaluated the toxicity, the effects on quality of life, and the antitumor activity of sc low-dose IL-2 in combination with LAN (90 mg every 28 days) in a series of 6 patients with symptomatic and advanced MTC. Results: The cytotoxicity of IL-2-activated peripheral blood mononuclear cells was significantly increased in TT cells treated with LAN or LAN plus IL-2 compared with that in TT cells without treatment. The therapy was well tolerated, and a statistically significant improvement of quality of life was observed in patients treated with the combination of LAN and IL-2. After 6 months of therapy, partial response and stable disease have been recorded in 2 and 3 patients, respectively, with a significant decrease in calcitonin levels in 3 patients. Conclusions: Both in vitro and in vivo evidence suggests that the combination of LAN and IL-2 may have a role in the management of advanced and symptomatic MTC. However, these preliminary data require further validation in larger randomized trials.
UR - http://www.scopus.com/inward/record.url?scp=84885212161&partnerID=8YFLogxK
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U2 - 10.1210/jc.2013-1443
DO - 10.1210/jc.2013-1443
M3 - Article
VL - 98
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 10
ER -