Biochemotherapy with thymosin α1, interleukin-2 and dacarbazine in patients with metastatic melanoma: Clinical and immunological effects

Lopez, Massimo; Carpano, Silvia; Cavaliere, R.; Lauro, Luigi Di; Ameglio, F.; Vitelli, Gaetano; Frasca, A. M.; Vici, Patrizia; Pignatti, F.; Rosselli, Michele; Rasi, Guido; Garaci, Enrico

doi:10.1093/oxfordjournals.annonc.a058979

Cited by 33 publications

(20 citation statements)

References 11 publications

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“…Consistent with the results of previous studies [29][30][31][32][33], our results suggest an association between thymalfasin therapy and restored immune function. In the current trial, patients who received thymalfasin in addition to TACE experienced no bacterial infections versus those who received TACE alone, among whom there were four infections including sepsis, cholecystitis, and bacterial peritonitis.…”

Section: Discussionsupporting

confidence: 93%

“…Thymalfasin promotes T-cell differentiation, enhances cytokine (IFN-c, IL-2, IL-3) production, and downregulates T-cell apoptosis [15][16][17][18][19][20][21][22][23]. It has been shown to decrease tumor cell growth both in vitro and in vivo [24][25][26][27][28] and has demonstrated therapeutic usefulness in several types of cancer, including non-small cell lung cancer and malignant melanoma [29][30][31]. One phase II study has been completed that examined the efficacy and safety of thymalfasin for the treatment of HCC [32].…”

Section: Introductionmentioning

confidence: 99%

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A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

et al. 2009

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Purpose Patients with advanced hepatocellular carcinoma (HCC) have few treatment options. Thymalfasin (thymosin a-1) is an immunomodulator that may increase response to ablative therapy through direct anti-tumor action or enhanced protection against infections. We compared transarterial chemoembolization (TACE) plus thymalfasin with TACE alone for unresectable HCC. Methods In this phase II, randomized trial, 25 patients received either TACE plus thymalfasin (1.6 mg SC, 5 times weekly; n = 14) or TACE alone (n = 11) for 24 weeks. Response was defined as transition to transplant eligibility or lack of disease progression through week 72. Survival was assessed through 24 months post-treatment. Results Eight of fourteen (57.1%) patients in the TACE ? thymalfasin group versus 5 of 11 (45.5%) patients in the TACE-only group became responders (P = 1.0). Four of fourteen TACE ? thymalfasin patients versus none of 11 TACE-only patients became eligible for transplant. Median overall survival time was 110.3 weeks for the TACE ? thymalfasin group versus 57.0 weeks for the TACE-only group (P = 0.45). Seven patients in each group experienced serious adverse events; there were no bacterial infections in the TACE ? thymalfasin group versus 4 in the TACE-only group. There were 3 deaths in the TACE ? thymalfasin group and 5 in the TACE-only group. Conclusions In patients with unresectable HCC, TACE ? thymalfasin resulted in numerically higher rates of survival and tumor response, including transplant candidacy, with fewer bacterial infections, than TACE alone. Treatment regimens for HCC including thymalfasin as an immunomodulator should be evaluated in larger trials.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

et al. 2009

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“…We recently reported that the decapeptide spanning residues 100-109 of proT 's carboxy-terminus (proT (100-109); TKKQK TDEDD) is the actual immunoactive area of the polypeptide and a most potent lymphocyte stimulator [89]. ProT (100)(101)(102)(103)(104)(105)(106)(107)(108)(109) induces PBMC proliferation and cytotoxicity, promotes the maturation of dendritic cells (DC), adopts a -sheet conformation, and its eVects are sequence-speciWc and comparable to that of intact proT . In an earlier study, we had shown that a slightly smaller segment (103)(104)(105)(106)(107)(108)(109) was also eVective in restoring the immune function of PBMC obtained from cancer patients in vitro [90].…”

Section: A-thymosins In Cancer Therapymentioning

confidence: 99%

“…The Wrst was conducted in 1985 by the group of Alan Goldstein [101], where in post-irradiated non-small cell lung (NSCL) cancer patients (42 individuals), administration of T 1 (900 g/m 2 /day) for 14 days showed normalization or maintenance of normal CD4+ T cell percentages and improvement of relapse-free and overall survival. Several years later in 1994 [102], patients with metastatic melanoma (46 in total) were treated with dacarbazine (DTIC), followed by 2 s.c. doses of T 1 (2 mg/dose) and IL-2. Complete response was recorded in 2 patients and stable disease in 5, median survival was 11 months, and the toxicity of the regimen was acceptable.…”

Section: A-thymosins In Cancer Therapymentioning

confidence: 99%

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Ioannou

Samara

Livaniou

et al. 2012

Cancer Immunol Immunother

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The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as "thymic hormones," are produced by this gland. Although the majority of them have not been proven to be thymus-specific, thymic peptides comprise an effective group of regulators, mediating important immune functions. Thymosin fraction five (TFV) was the first thymic extract shown to stimulate lymphocyte proliferation and differentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin α (proTα) and thymosin α1 (Tα1) showed that they are of clinical significance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeficiencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their effect are yet not fully elucidated, proTα and Tα1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proTα, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of Tα1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proTα into the clinical setting.

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“…Two small pilot studies showed beneficial effects compared to historical control when Ta1 treatment was added to Dacarbazine (DTIC) chemotherapy combined with IL-2 [165] or IFN-alpha [166].…”

Section: Melanomamentioning

confidence: 99%

Thymosin Apha 1–A Peptide Immune Modulator with a Broad Range of Clinical Applications

King¹

2013

Clin Exp Pharmacol

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Biochemotherapy with thymosin α1, interleukin-2 and dacarbazine in patients with metastatic melanoma: Clinical and immunological effects

Abstract: The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity. However, even more active regimens are needed, and the interactions between thymic hormones and cytokines should be further explored.

Cited by 33 publications

References 11 publications

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Thymosin Apha 1–A Peptide Immune Modulator with a Broad Range of Clinical Applications

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