[Psychological nursing for genital herpes patients receiving acyclovir plus thymosin and its effect on the incidence of adverse reactions].

OBJECTIVE: To explore the application of psychological nursing in patients with genital herpes receiving acyclovir combined with thymosin and its effect on the incidence of adverse reactions. METHODS: A total of 160 patients with genital herpes treated with acyclovir plus thymosin in our hospital from January 2016 to December 2018 were randomly allocated to receive conventional nursing (the control group, n = 80) and psychological nursing (the trial group, n = 80). Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were used to evaluate the anxiety and depression of the patients, and comparisons were made between the two groups of patients in their SAS and SDS scores, the incidence of adverse reactions and their satisfaction with nursing intervention. RESULTS: After nursing intervention, the patients of the trial group, compared with the controls, showed significantly lower SAS scores (39.05 ± 2.97 vs 45.71 ± 3.36, P < 0.01), SDS scores (41.74 ± 2.86 vs 47.28 ± 3.95, P < 0.01), and incidence of adverse reactions (22.50% vs 47.50%, P < 0.05), but a markedly higher rate of satisfaction with nursing intervention (95.00% vs 77.5%, P < 0.01). CONCLUSIONS: Psychological nursing can reduce the incidence of adverse reactions in genital herpes patients receiving acyclovir combined with thymosin and meanwhile improve the mental status of the patients by alleviating their anxiety and depression.

Effect and analysis of ulinastatin combined with thymosin on cardiopulmonary function and delirium in sepsis patients.

The aim of this study was to explore the clinical effect of ulinastatin combined with thymosin in patients with sepsis and its influence on cardiopulmonary function and delirium. Sixty-eight sepsis patients were enrolled as study subjects. The patients were randomly divided into a symptomatic treatment group (n=34) and a combined treatment group (n=34) on the basis of random number table. The two groups were first operated and then, the symptomatic treatment group was given symptomatic support treatment, whilst the combined treatment group was treated with ulinastatin and thymosin on the prerequisite of the symptomatic treatment group. After 7 days of treatment, the evaluation of the curative effect was performed, followed by the comparison of the cardiopulmonary function, immune level and safety between the two groups of patients. The cardiac index and oxygenation index of the combined treatment group were higher than those of the symptomatic treatment group 7 days after treatment (P<0.05). Whereas, the levels of plasma D-dimer and cTnI were lower than those of the symptomatic treatment group (P<0.05). In addition, CD3+, CD4+, CD4+/CD8+ levels of the combined treatment group were higher than those of the symptomatic treatment group 7 days after treatment (P<0.05). On the contrary, CD8+ levels of the combined treatment group were lower than those of the symptomatic treatment group 7 days after treatment. There was no significant (P>0.05) difference in drug safety between the two groups during treatment.

Impact of the immunomodulating peptide thymosin alpha 1 on multiple myeloma and immune recovery after hematopoietic stem cell transplantation.

Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma cells in the bone marrow and causes several immune alterations in patients. Thymosin α1 (Tα1) is a thymic peptide that has been associated with immuno-stimulating properties. In addition, this peptide exerts anti-tumor effects in several cancer types. Beneficial effects of Tα1 administration have also been shown on immune reconstitution after hematopoietic stem cell transplantation (HSCT), a current treatment modality in hematological malignancies including MM. In this study, we observed a slight reduction in the proliferation of murine and human MM cell lines in the presence of Tα1 in vitro. However, using two immunocompetent murine MM models (5TGM1 and MOPC315.BM), we did not observe any impact of Tα1 administration on MM development in vivo. Furthermore, no beneficial effects of Tα1 treatment were observed on lymphocyte immune reconstitution after transfusion of human hematopoietic stem cells into immunodeficient mice. In conclusion, despite direct effects of Tα1 on human MM cell line proliferation in vitro, Tα1 did not exert anti-myeloma effects in vivo in the two murine models tested. Moreover, Tα1 failed to improve immune recovery in a xenogeneic HSCT model.

Efficacy of thymosin α-1 plus peginterferon α-2a combination therapy compared with peginterferon α-2a monotherapy in HBeAg-positive chronic hepatitis B: a prospective, multicenter, randomized, open-label study.

OBJECTIVE: Thymosin α-1 plus interferon α-2a offers superior efficacy over interferon α-2a alone in patients with chronic hepatitis B. The aim was to compare the antiviral efficacy of thymosin α-1 plus peginterferon α-2a and peginterferon α-2a alone in HBeAg-positive chronic hepatitis B patients. MATERIALS AND METHODS: HBeAg-positive CHB patients were enrolled in this prospective, randomized, open-label study. Fifty-one patients were assigned to either combination (26 patients; 180 µg of peginterferon α-2a weekly for 48 weeks and 1.6 mg of thymosin α-1 twice a week for the first 12 weeks) or monotherapy (25 patients; 180 µg of peginterferon α-2a weekly for 48 weeks) groups. RESULTS: The rates of the combined response, defined as HBeAg seroconversion, HBV DNA suppression, and normalization of serum ALT, were 4/26 (15.4%) and 3/25 (12.0%) for the combination group and the monotherapy group at the end of treatment (p = 0.725), and 6/26 (23.1%) and 5/25 (20.0%) at the end of follow-up (p = 0.789), respectively. Based on multiple logistic regression analysis, a >2 log10 IU/mL reduction of HBV DNA at week 12 was identified as an independent predictor for combined response (OR, 9.72; 95% CI, 1.33-71.06; p = 0.025) at the end of follow-up. A lower pretreatment HBV DNA level (≤ 7 log(10) IU/mL) was another predictor for combined response (OR, 9.64; 95% CI, 1.23-75.32; p = 0.031). No significant differences in adverse events were observed. CONCLUSIONS: The short-term addition of thymosin α-1 was not superior to peginterferon α-2a alone in HBeAg-positive CHB patients on the basis of antiviral efficacy.

Therapeutic effect of Xuebijing combined with thymosin on hemorrhagic fever with renal syndrome: A protocol of systematic review and meta-analysis.

BACKGROUND: The goal of this study is to assess the therapeutic effect of Xuebijing combined with thymosin (XBJ-T) for the treatment of patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We will search the electronic databases of Cochrane Library, PUBMED, EMBASE, PsycINFO, Scopus, Opengrey, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Google scholar, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database from inception to the present. No language and publication status will be employed in this study. Based on the predefined eligibility criteria, selection of study and data extraction will be performed by 2 researchers independently. Study quality will be assessed using Cochrane risk of bias tool. We will apply RevMan 5.3 software to pool and analyze the extracted data. RESULTS: This study will assess the therapeutic effect of XBJ-T for the treatment of patients with HFRS. CONCLUSION: The findings of this study may provide systematic evidence to judge whether XBJ-T is an effective and safety intervention for HFRS. STUDY REGISTRATION NUMBER: INPLASY202040068.

Efficacy of triple therapy with thymalfasin, peginterferon alpha-2a, and ribavirin for the treatment of hispanic chronic HCV nonresponders.

BACKGROUND/AIMS: Thymalfasin has shown efficacy in the treatment of chronic HCV infection. The aim of this study was to evaluate the efficacy and tolerability of triple therapy with thymalfasin, peginterferon alpha-2a (PEG-IFN alpha-2a), and ribavirin in Hispanic patients with chronic viral hepatitis C who were nonresponders to prior treatment with interferon alfa (IFN-alpha)/ribavirin. METHODS: In this open-label study, 40 subjects received thymalfasin (1.6 mg twice a week), PEG-IFN alpha-2a (180 microg once a week), and ribavirin (800-1,000 mg/day) for 48 weeks. All patients had positive HCV RNA by PCR analysis, abnormal levels of ALT, compensated hepatic disease, and liver biopsy with chronic damage. RESULTS: Viral response was observed in 52.5% patients at week 12 and 50% at week 24. Of the per protocol group, 52.6% showed an end-of-treatment response at week 48 and 21.1% achieved an SVR at week 72. Among genotype 1 patients, 23.5% achieved an SVR at week 72. A reduction of the dose of PEG IFN alpha-2a and ribavirin was required. Thymalfasin was well tolerated without dose reduction. CONCLUSION: Triple therapy with thymalfasin, PEG IFN alpha-2a, and ribavirin is an effective treatment option for difficult-to-treat HCV patients who are refractory to prior conventional treatment, with adequate tolerability.

Thymalfasin for the treatment of chronic hepatitis C infection.

The purpose of this review article is to examine previous and ongoing studies of thymalfasin in combination with peginterferon-alpha2a and peginterferon-alpha2a plus ribavirin in difficult-to-treat hepatitis C virus (HCV) patients. The following studies will be reviewed in detail: (1) Sherman and colleagues conducted a study in 109 HCV RNA positive HVC patients comparing the combination of thymalfasin + IFN versus IFN alone versus placebo. (2) Rustgi et al. evaluated the efficacy and safety of thymalfasin and peg-IFN-alpha2a in 31 genotype 1, high viral load, HCV nonresponders in a 12-week viral kinetic study. (3) Di Bisceglie, Sherman et al. performed a study of previous HCV nonresponders being retreated with either peginterferon-alpha2a plus thymalfasin or peginterferon-alpha2a plus placebo. (4) Poo and colleagues in Mexico evaluated triple combination therapy using thymalfasin, peginterferon-alpha2a, and ribavirin for the treatment of Hispanic HCV nonresponders.

A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B.

Combination therapy between two immunomodulators used for treatment of chronic hepatitis B was explored based on reported therapeutic efficacy of interferon-alpha, and thymosin-alpha1 as monotherapeutic agents to determine if combination therapy was superior to interferon alone. This double-blinded, randomized, placebo-controlled trial compares the addition of thymosin-alpha1, 1.6 microg taken three times per week (combination therapy) or thymosin placebo (monotherapy) to lymphoblastoid interferon (Wellferon), 5 million international units (MIU) taken three times per week, for 24 weeks. Entry criteria included positive hepatitis B e antigen (HBeAg); alanine aminotransferease (ALT) > or = 1.5 x upper normal limit, but < or = 10 x upper normal limit; positive HBV DNA; absence of cirrhosis; treatment naivety and no co-morbid factors. A total of 98 HBeAg-positive patients were recruited, of which 48 were randomized to combination therapy and 50 to monotherapy. The primary endpoint was the loss of HBeAg at 72 weeks. The secondary endpoints were HBeAg seroconversion, normalization of ALT, loss of HBV DNA and improvement in histology. The HBeAg loss was 45.8% and 28.0% for combination therapy and monotherapy, respectively (difference, 17.8%; 95% CI -1.2%-35.3%, P = 0.067). There was a trend towards HBeAg loss when using combination therapy. There were also no statistically significant differences between the different therapies with respect to the secondary endpoints of HBeAg seroconversion, changes in histology, normalization of ALT or loss of HBV DNA. In conclusion, this trial showed a 17.8% improvement in HBeAg loss rates using combination therapy over interferon monotherapy. This could clinically indicate a potential important difference that would need confirmation in subsequent trials.

Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: a randomized controlled study.

AIM: To observe the efficiency and safety of thymosin-alpha1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-alpha1, twice a week (T-alpha1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-alpha) each day for fifteen days, then three times weekly (IFN-alpha group) for six months. The results between two groups treated with and the group untreated with IFN-alpha which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P>0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-alpha1 group and in 15 of 33 (45.5%) patients in the IFN-alpha group (chi2=1.36, P>0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-alpha1 group and in 9 of 33 (27.3%) patients in the IFN-alpha group (chi2=2.93, P>0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-alpha which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-alpha group at the end of therapy (1 of 30 vs 15 of 33, chi2=14.72, P<0.001) and in the T-alpha1 group at the end of follow-up (1 of 30 vs 14 of 29, chi2=15.71, P<0.001). In T-alpha1 and IFN-alpha treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-alpha1 group were significantly higher than those in the IFN-alpha and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-alpha1 group than in the IFN-alpha group. Unlike IFN-alpha, T-alpha1 was well tolerated by all patients, and no side effects appeared in T-alpha1 group. CONCLUSION: The results suggest that a 6-mo course of T-alpha1 therapy is effective and safe in patients with chronic hepatitis B. T-alpha1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-alpha1 is better tolerated than IFN-alpha and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.

Randomized trial of combined modality therapy with and without thymosin fraction V in the treatment of small cell lung cancer.

A randomized trial of thymosin fraction V (60 mg/m2 s.c. twice weekly) given during induction chemotherapy and radiation therapy was performed in 91 patients with small cell carcinoma of the lung. Induction chemotherapy consisted of four cycles of an alternating combination of drugs (cyclophosphamide/Adriamycin/vincristine and cisplatin/etoposide). Radiation to the primary complex was given to patients with limited disease. All patients received prophylactic cranial irradiation. There were 35 patients with limited disease (18 randomized to thymosin and 17 to no thymosin) and 56 with extensive disease (28 thymosin and 28 no thymosin). Pretreatment immunological parameters were comparable between the two groups. For limited disease patients the overall response rate was 100%, including 66% (21 of 32) complete responders. The median duration of response was 19 mo (range, 5-57 mo) and survival 21 mo (range, 4 days to 57 mo). The 3-yr survival was 32%. For ED patients the overall response rate was 95% with 29% (13 of 48) complete. The median duration of response was 10 mo and the median duration of survival 12 mo with 13% alive at 2 yr. A comparison of the thymosin-versus no thymosin-treated patients revealed no difference in response rate, response duration, or survival whether analyzed as a whole or by extent of disease. An analysis based on pretreatment immune function and total white blood cell and absolute lymphocyte count revealed no difference in the survival distributions. No differences in the pattern of toxicity were observed between the thymosin- versus no thymosin-treated patients. The addition of thymosin fraction V during induction chemotherapy and consolidation radiotherapy did not alter outcome.

Thymosin Beta 4: A Potential Novel Therapy for Neurotrophic Keratopathy, Dry Eye, and Ocular Surface Diseases.

Chronic ocular surface diseases such as dry eye, blepharitis, and neurotrophic keratopathies represent a significant and a growing therapeutic challenge. The basis of this expanding prevalence is multifactorial and may due to issues such as an aging population, an increasing use of video display terminals, and increases in frequency of refractive surgeries. The growing incidence of diseases such as diabetes may also be a contributing factor. Current treatments for ocular surface disease include artificial tears, lubricants, tear duct plugs, steroids, antibiotics, cyclosporine, scleral lenses, and serum tears. Treatment choices depend on the type and severity of the disease, but in general positive outcomes are limited because many of these treatments do not fully address the underlying disease process or promote mechanisms that facilitate long-term wound repair. From minor corneal injuries to more severe inflammatory-mediated pathologies, clinicians need agents that promote corneal healing and reduce the inflammatory response to prevent visual disturbances and improve quality of life. A focus on treatments that reduce the inflammatory responses while accelerating corneal epithelial growth would represent a major step forward from current treatment options. Increasing evidence suggests that thymosin beta 4 (Tß4), a naturally occurring polypeptide, can elicit this spectrum of therapeutic responses: a rapid corneal reepithelialization and a reduction in corneal inflammation. This chapter serves as a review of standard therapies as well as recent advancements in the development of newer therapies that includes the use of Tß4 that is proving to be an exciting new agent for the management of ocular surface disease.

Thymosin ß4 Promotes Dermal Healing.

No agent has been identified that significantly accelerates the repair of chronic dermal wounds in humans. Thymosin beta 4 (Tß4) is a small, abundant, naturally occurring regenerative protein that is found in body fluids and inside cells. It was found to have angiogenic and antiinflammatory activity and to be high in platelets that aggregate at the wound site. Thus we used Tß4 initially in dermal healing. It has since been shown to have many activities important in tissue protection, repair, and regeneration. Tß4 increases the rate of dermal healing in various preclinical animal models, including diabetic and aged animals, and is active for burns as well. Tß4 also accelerated the rate of repair in phase 2 trials with patients having pressure ulcers, stasis ulcers, and epidermolysis bullosa wounds. It is safe and well tolerated and will likely have additional uses in the skin and in injured organs for tissue repair and regeneration.

Thymosin ß4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial.

PURPOSE: Standard therapies for severe dry eye are limited and fail to resolve the problem. The purpose of this study was to evaluate the safety and efficacy of Thymosin ß4 eye drops (RGN-259) as a novel therapy for severe dry eye disease (including that associated with graft vs. host disease). METHODS: A small, multicenter, randomized, double-masked, placebo-controlled 56-day phase 2 clinical trial including a 28-day follow-up at 2 US sites. Nine patients with severe dry eye were treated with either RGN-259 (0.1%) or vehicle control 6 times daily over a period of 28 days. Dry eye sign and symptom assessments, such as ocular discomfort (using the OSDI questionnaire) and corneal fluorescein staining (using the NEI workshop grading system), were evaluated at various time points. RESULTS: Statistically significant differences in both symptom and sign assessments, were seen at various time points throughout the study. Of particular note at day 56, the RGN-259-treated group (12 eyes) had 35.1% reduction of ocular discomfort compared with vehicle control (6 eyes) (P = 0.0141), and 59.1% reduction of total corneal fluorescein staining compared with vehicle control (P = 0.0108). Other improvements seen in the RGN-259-treated patients included tear film breakup time and increased tear volume production. CONCLUSIONS: In this small trial, RGN-259 eye drops were safe and well tolerated and met key efficacy objectives with statistically significant symptom and sign improvements, compared with vehicle control, at various time intervals, including 28-days posttreatment. CLINICAL TRIAL REGISTRATION--URL: http://www.clinicaltrials.gov. Unique identifier: NCT01393132.

A multicenter, randomized, observation-controlled clinical trial to evaluate the efficacy and safety of thymalfasin adjuvant therapy in patients with HBV-related HCC after curative resection - first announcement of the protocol.

Hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide, is a disease of immune microenvironment. Chronic Hepatitis B virus (HBV) infection, also an immune-related disease, is the major etiological factor for HCC especially in Asia. As an immune regulator, which has pleiotropic activities on T cells, nature killer cells and dendritic cells and so on, the efficacy of thymalfasin on HCC patients has been proven by several pilot studies as an adjuvant therapy. Combination of thymalfasin significantly improved survival and prolonged the time to tumor recurrence in patients who received transcatheter arterial chemoembolization after tumor resection. An improvement in patients' immunity has also been demonstrated. However, there is no large-scale randomized controlled study so far in resectable HCC patients. To confirm the role of thymalfasin adjuvant therapy in patients with HBV-related HCC after curative resection, a large-scale multicenter randomized controlled trial has been planned in China to investigate the effect of thymalfasin (1.6 mg twice a week for 12 months) on 2-year recurrence-free survival rate and tumor immune microenvironment. Here is the first announcement of the study protocol (ClinialTrials.gov Identifier: NCT02281266).

Thymosin alpha1. SciClone Pharmaceuticals.

Thymosin alpha1 (Talpha1), a synthetic 28-amino acid peptide with multiple biological activities primarily directed towards immune response enhancement, was originally developed by Alpha 1 Biomedicals for the treatment of hepatitis B virus (HBV) infection. SciClone developed and launched Talpha1, under the trade name Zadaxin, for the treatment of HBV and hepatitis C virus (HCV) infections. The drug is also being developed for the treatment of non-small cell lung cancer (NSCLC), hepatocellular carcinoma, AIDS and malignant melanoma. Talpha1 is able to potentiate the action of cytokines and also reduce the hematological toxicity of cytotoxic drug therapy (cyclophosphamide-, 5-fluorouracil-, dacarbazine- or ifosfamide-based regimens). These studies also demonstrated the mechanism of action of Talpha1 and its role as an immune system enhancer. By July 2001, it was in phase III trials in the US in combination with PEGylated interferon-alpha, and later the same month it was approved in the Philippines. SciClone received expanded approval for HBV and HCV infection in Mexico in July 2001. Talpha1 has been launched in Argentina, China, Peru, the Philippines and Singapore for the treatment of chronic HBV infection. The product subsequently received expanded approval for the treatment of both HBV and HCV infection in Argentina. Marketing approval was granted in India for HBV infection in February 2001. The company was working to expand this approval to include HCV infection. In March 2000, approval for treatment of HBV infection was granted in Thailand, Laos and Malta. Approval was also granted in Sri Lanka and Brunei in August 1999. In September 2000, SciClone announced that approval had been expanded to include the treatment of HCV infection as well as the previously approved HBV indication in both Peru and Sri Lanka. In January 1999, SciClone received approval for Talpha1 in Venezuela for the treatment of HBV and HCV infection. The company also filed a marketing application in New Zealand for Talpha1 to treat HBV infection. The drug was approved in South Korea in April 2000, as an influenza vaccine adjuvant and this was expected to be expanded to indude use for treatment of both HBV and HCV infections. In July 2001, it was approved in In September and October 2000, SciClone was granted patents in Mexico and Canada, respectively, for the use of Talpha1 for the treatment of HCV infection. In June 2000, SciClone was issued a Notice of Allowance by the US Patent and Trademark Office for use of Talpha1 in the treatment of HBV infection. The EPO granted a patent, exclusively licensed to SciClone, for the use of Talpha1 as a monotherapy or in combination with interferon, to treat for HCV infection. In April 2001, SciClone received a Notice of Allowance for a US patent covering newly described analogs of Talpha1. The patent gave the Philippines as an adjuvant to chemotherapy for the treatment of various cancers. In December 2001, Talpha1 entered a phase 1 trial program in Europe, with patient enrolment planned for 2002. SciClone exclusive composition-of-matter rights to several families of Talpha1 analogs that could have proprietary therapeutic or biologic distinctions from Talpha1. The company was issued US patents covering the use of Talpha1 for the treatment of HCV infection in August 1998 and the treatment of HBV infection in September 1999. A Notice of Allowance for a second US patent covering the use of Talpha1 was issued in October 1999. In April 1999, SciClone received allowance of a patent from the EPO covering the use of Talpha1 in small cell and non-small cell lung cancer. In August 2001, SciClone received a notice of allowance for patent protection in Japan covering the use of Talpha1. The patent, which extends until 2012, also covers the use of Talpha1 in combination with interferon-alpha for the treatment of HCV infection. SciClone was previously granted a Japanese patent for the use of Talpha1 in the treatment of HBV infection.

In vitro and in vivo studies with thymosin in cancer patients.

Thymosin, fraction V, prepared by the method of Goldstein et al., was studied in in vitro lymphocyte cultures with cells obtained from normal subjects and patients with disseminated cancer. Thymosin lowered blastogenic activity in some patients, did not affect it in others, and increased counts in still others. There was a statistically significant depression in baseline (prethymosin) counts from both normals and patients when individuals whose counts increased in the presence of thymosin were compared with other subjects. We conclude that thymosin tended to raise depressed blastogenesis into the normal range without causing supranormal activity or without itself acting as a mitogen or antigen. Eighty-two in vivo courses in thymosin were given to 32 patients. Analysis of the first thymosin courses in these 32 patients shows that immunologic reconstitution occurred in patients with originally depressed T-cell function and numbers, whereas little change was apparent in patients with initially intact tests of T-cell activity. Clinical effects were equivocal; however, no systematic clinical trial was conducted. Toxicity was minimal (four of the 32 patients); in each case, it consisted of inflammation at the injection site. The in vitro and in vivo results of this study suggest that thymosin therapy modulates and partially normalizes T-lymphocyte numbers and function.

Combined treatment with thymosin-alpha1 and low-dose interferon-alpha after ifosfamide in non-small cell lung cancer: a phase-II controlled trial.

22 patients with advanced non-small-cell lung cancer were randomized to receive chemotherapy (ifosfamide) or chemotherapy followed by thymosin alpha1 + low-dose IFNalpha. Chemo-immunotherapy induced an enhanced response rate compared with chemotherapy alone (33% and 10% respectively). Although these differences were not significant, the difference in time to progression was (p=0.0059). CD4+, CD8+ and NK cell counts were significantly depressed after two cycles of chemotherapy, while no difference in cell count were seen in chemo-immunotherapy treated patients. Hematologic toxicity was reduced by the immunotherapy, with no grade 3/4 toxicity seen compared to 50% in patients treated with chemotherapy alone.

Limited small-cell lung cancer: do favorable short-term results predict ultimate outcome?

Advances in the treatment of limited small-cell lung cancer (L-SCLC) have led to improved short-term outcome. However, it is not clear how well this predicts the ultimate fate of the patients. This may be affected by late relapse of SCLC, the development of second malignancies, and the long-term toxicity of therapy. To address this issue we report follow-up in excess of 5 years on a cohort of 36 patients who had high short-term survival resulting from treatment with chemotherapy combined with cranial and thoracic irradiation. All patients were followed until death or the time of analysis. The initially promising result of 31% survival at 3 years, was reflected in survival from SCLC of 27% at 5 years, and 23% at 9 years. However, when death from all causes was analyzed, survival was only 19% at 5 years and 7% at 9 years. There were 2 survivors disease-free at 7 and 8 years; 7 patients died of other causes without any evidence of SCLC. Among those not dying of SCLC, 4 patients developed second malignancies with a risk of 22% at 3.2 years and 50% at 8 years. Clinical neurotoxicity developed in 3 patients. These data suggest that cure of SCLC is possible in a modest proportion of patients with limited disease, but that the survivors are at significant risk of developing second malignancies which emerge as the most common cause of death during prolonged follow-up. Successful outcome of treatment is further hampered by the occurrence of neurotoxicity. Clinical strategies to prevent these sequelae of therapy are discussed.

Pharmacokinetics of thymosin alpha1 after subcutaneous injection of three different formulations in healthy volunteers.

OBJECTIVE: Thymosin alpha1, an immunomodulatory endogenous peptide, has been shown to be effective in the treatment of chronic hepatitis B and C. In this study, single- and 5-day multiple-dose pharmacokinetics were characterized in nine Caucasian volunteers after subcutaneous administration of 900 microg/m2 thymosin alpha1. METHODS: Using a randomized, 3-way crossover design three available drug formulations were compared: Zadaxin (SciClone), Timosina (Sclavo), and Thymosin alpha1 (Tal-HLR; Hoffmann La Roche). AUC, Cmax, t(max), t(1/2), Cl/f, and the volume of distribution, V(Z)/f, were derived by model-independent methods. RESULTS: Endogenous serum concentrations were below the limit of quantification (0.10 microg/l) of the enzyme-linked immunosorbent assay method in most subjects. Thymosin alpha1 was well absorbed with a mean t(max) between 1-2 hours from all galenic formulations. Cmax concentrations of 30 to 80 microg/l and AUC(0-infinity) from 95 to 267 microg x h/l did not differ between single- and multiple-dose administration of all drugs. This apparent lack of accumulation was supported by the short elimination half-life of less than 3 hours. As indicated by a V(Z)/f in the range of 30-40 l, thymosin alpha1 appears to distribute within the extracellular volume. AUC and Cmax were similar for Zadaxin and T alpha1-HLR, but higher after administration of Timosina. CONCLUSION: Thymosin alpha1 kinetics from this study are comparable to those previously obtained in Japanese volunteers or cancer patients, but may be influenced by the drug formulation used.

Two immune boosters against hepatitis C.

AIDS: Hepatitis C (HCV) can cause liver damage or liver cancer, and it is doubtful that antiviral drugs alone will be able to cure HCV. Because of the limitations of antiviral drugs, researchers are studying ways to enhance the immune system's ability to fight HCV. The current standard therapy for treating HCV is to use Interferon-alpha, although this may change to a combination of Interferon-alpha and Ribavirin. However, Ribavirin can have detrimental effects on bone marrow and may not be tolerated by some patients. Results of a study are presented.^ieng