The effect of thymopentin add-on in hepatitis B e antigen positive chronic hepatitis B after virus suppression by peginterferon plus entecavir therapy.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) was positively correlated with serological hepatitis B surface antigen (HBsAg) levels in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients. We evaluated whether Thymopentin (TP5) and interferon (IFN-a) had a synergic effect on HBV cccDNA and the effect of TP5 addition therapy on HBsAg clearance in CHB patients. Real-time PCR experiments were performed to test cccDNA in HepG2.2.15 cells. 45 HBeAg-positive CHB patients had been distributed into two groups randomly. Treatment group: 23 patients were treated with a 24-week TP5 on the basis of the treatment entecavir (ETV) and peginterferon alfa-2a (PegIFN alpha-2a). Control group: 22 patients were treated with ETV and PegIFNa-2a. The study period was 72 weeks. In HepG2.2.15 cells, TP5 5ug/ml and 10ug/ml respectively combined with IFN-a 2ku/ml could potently inhibit cccDNA level at 72 hours (P<0.05). In clinical study, mean HBsAg levels in two groups are not significantly different at different time points (p=0.112). However, changes of mean HBsAg levels in TP5 add-on group at different time points are significantly different (p<0.05). Patients with HBsAg levels <1500IU/ml in control group had higher HBsAg levels compared with patients with HBsAg levels <1500IU/ml in TP5 add-on group (P=0.019). The latter had the most pronounced HBsAg reduction. TP5 and IFN had a synergic effect on inhibiting cccDNA levels in HepG2.2.15 cells; Patients in treatment group showed no extra side effects compared with the control group. 24 weeks TP5 add-on treatment was safe and had a tendency to accelerate the decline of HBsAg when HBV-DNA was undetectable.

Myristic acid-modified thymopentin for enhanced plasma stability and immune-modulating activity.

Natural albumin ligand (fatty acids)-conjugated peptides can rapidly bind to circulating albumin and form complexes to control the release of peptides. The purpose of this study was to prolong the half-life and immune-modulating effects of thymopentin (TP5) by using the albumin binding strategy. We synthesized myristic acid-modified TP5 (TP5-MA) by conjugating a myristic acid-acylated lysine to a permissive site of TP5, which improved the albumin binding affinity of TP5-MA and dramatically enhanced its stability in human plasma. We observed well-preserved bioactivities of TP5-MA in RAW264.7 macrophages using a tumor necrosis factor (TNF)-α stimulation assay. Moreover, the prolonged immune-modulating effect of TP5-MA was confirmed by the normalized CD4+/CD8+ ratio in immune-depressed rat models, which resulted in a reduced administration frequency (twice per week). In general, the enhanced pharmacokinetic and pharmacodynamic properties of TP5-MA make it a promising product for the treatment of immunodeficiency diseases.

Repeated transfusions of autologous cytokine-induced killer cells for treatment of haematological malignancies in elderly patients: a pilot clinical trial.

The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine-induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL-2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal antibody. The autologous CIK cells (2-3 × 10(9)) were transfused back to patients, followed by a subcutaneous injection of IL-2 (1 mU/day) for 10 consecutive days. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum ß2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow-up, the mean survival time was 20 months. Transfusion with autologous CIK cells plus rhIL-2 treatment is safe and effective for treating haematological malignancies in elderly patients.

Thymic peptides for treatment of cancer patients.

BACKGROUND: Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy. OBJECTIVES: To evaluate the effectiveness of pTE and sTP for the management of cancer. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010). SELECTION CRITERIA: Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis. MAIN RESULTS: We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α(1)). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10  for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α(1) the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23,  P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias. AUTHORS' CONCLUSIONS: Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α(1), there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.

[Mediation of cellular immune response by TP5 in pathogenesis of myasthenia gravis].

OBJECTIVE: To evaluate the effects of TP5 upon the production of IFN-gamma and different T cell subsets by human peripheral blood mononuclear cells (PBMCs) from patients with myasthenia gravis (MG) and to provide experimental rationales for TP5 in clinical therapy of MG. METHODS: PBMCs were isolated from peripheral blood of MG individuals and cultured with anti-CD3. The level of IFN-gamma in culture supernatants was examined by ELISA. The subsets and frequency of IFN-gamma-producing cells were examined at a single-cell level by flow cytometry. RESULTS: After PBMCs stimulation with anti-CD3 and TP5 (300 microg/ml), the level of IFN-gamma expression was significantly inhibited (P(child) = 0.0001, P(adult) = 0.01); and the level of IFN-gamma expression from normal adult and child controls was also significantly inhibited (P(child) = 0.009, P(adult) = 0.0001). In addition, the inhibition of TP5 on the production of IFN-gamma by PBMCs from MG children was lower compared with normal child control. But as compared with normal adult control, the inhibition of TP5 showed no significant difference in MG adults (P(adult) = 0.481). TP5 inhibited the expression of IFN-gamma by CD8+ T cell and CD4+ T cell. CONCLUSION: TP5 can inhibit the response of cellular immune by decreasing the production of IFN-gamma in MG consequence display that the level of IFN-gamma significant decreased with the addition of TP5 and anti-CD3. But after considering the age, the level of IFN-gamma in MG children was no as much inhibited as normal child. TP5 inhibits the expression of IFN-gamma by CD8+ T and CD4+ T cells.

[Thymopentin 5 in treatment of relapse after extended thymectomy: a randomized comparative clinical trial of 135 patients with myasthenia gravis].

OBJECTIVE: To investigate the effect of thymopentin 5 (TP5) combined with immunosuppressive agents in treatment of relapse after extended thymectomy in patients with myasthenia gravis (MG). METHODS: One hundred thirty-five MG patients who were to undergo extended thymectomy, 62 adults and 73 children, were randomly assigned to 2 groups: non-TP5 group (n = 60) treated with intramuscular injection of prednisone + pyridostigmine daily for 3 months as a basic treatment, and TP5 group (n = 73), treated with prednisone + pyridostigmine + TP5 for 3 months. Follow-up was conducted for more than 1 year. RESULTS: The remission rates of children in the TP5 group at different time points were all markedly higher than those in the non-TP5 group, and the remission rates of children in the TP5 group during the period of 2 months to 2 years after thymectomy were all significantly higher (all P < 0.05). And the remission rates of the adults of the TP5 group during the period of 6 months to 2 years after thymectomy were all significantly higher than those of the non-TP5 group (all P < 0.05). In the pediatric cases the withdrawal rate of the TP5 group was significantly higher, and the relapse rate was significantly lower than those of the non-TP5 group. No side effect developed during the follow-up. CONCLUSION: TP5 is effective in reducing relapse and has a higher drug withdrawal rate, especially among children.

[Study on the efficacy and safety of high dose thymopentin combined with trans-artery chemoembolization for primary liver cancer].

OBJECTIVE: To evaluate the efficacy and safety of high doses of thymopentin (10 mg/d) combined with transartery chemoembolization for primary liver cancer. METHODS: Fifty primary liver cancer patients were randomly divided into two groups: therapeutic and control group, and all were treated with transfemoral artery chemoembolization (TACE) with oxaliplatin 150 mg, pharmorubicin 50 mg, 5-Fu 750 mg, CF 300 mg and lipiodol 20 ml. Therapeutic group (25) were added 10 mg thymopentin daily after TACE: i.v. on dl - d5, and im on D6 - D21. RESULTS: There was a significant difference in adverse effect and toxicity such as naupathia,fever, swirl, asthenia observed between two groups (P < 0.05). No difference in either pre- or post-chemotherapy peripheral blood examination and biochemical assay was found between two groups (P > 0.05). In control group, CD4+ cell was 37.92% +/- 8.71% in pre-treatment, which decreased to 29.16% +/- 8.21% in post-treatment with a significant difference (P < 0.01), whereas there was no evident difference in CD4+ cell between pre-treatment and post-treatment in the treatment group. CONCLUSION: Transartery chemoembolization combined with high dose of thymopentin in the treatment for primary liver cancer is effective and safe, and can significantly improve the immune function and the chemotherapy tolerance.

[Clinical trial to verify the value of the CD14(+) monocyte human leukocyte antigen DR as a marker in evaluating immunosuppression in patients with severe sepsis].

OBJECTIVE: To verify that CD14(+) monocyte human leukocyte antigen DR (HLA-DR) may serve as a reliable index for immunosupression, and for prediction of prognosis as well as to evaluate the efficacy of Thymopentin (TP-5) to enhance immunologic function in patients with severe sepsis, and to evaluate the validity of compensatory anti-inflammatory response syndrome (CARS). METHODS: Patients in a SICU with symptoms and signs of severe sepsis conforming to the criteria set forth by ACCP/SCCM were enrolled in this clinical trial. CD14(+) monocyte HLA-DR was determined by flow cytometry. To those with HLA-DR<30%, TP-5, 1 mg, q.d. was administered till HLA-DR raised or death occurred. Before the treatment was begun and ended, CD14(+) monocyte HLA-DR(+) and cytokines[tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, IL-13] were respectively measured. RESULTS: Totally, 20 patients were enrolled in this study. Among them 15 survived and 5 died. After treatment with TP-5, CD14(+) monocyte HLA-DR was elevated in almost all the patients, including the nonsurvivors. However, only a statistically significant difference between the initial values and the final values was noted in the survivors. The levels of TNF-alpha and IL-6 dropped significantly concomitantly with the elevation of the CD14(+) monocyte HLA-DR in survivors. On the contrary, in the patients who died there was a tendency of an elevation of levels of these cytokines. No significant difference was found between the initial and final levels of both IL-10 and IL-13 with the treatment. CONCLUSION: 1. It was reconfirmed that the CD14(+) monocyte HLA-DR could be a reliable and valuable index to judge immunosupression in septic patients and determine the effectiveness of immunostimulative therapy. 2. It was reconfirmed that the level of CD14(+) monocyte HLA-DR can serve as an index to predict the outcome of septic patients. 3. TP-5, as a new immunostimulative agent used in sepsis, might be effective to revert immunosupression. However, a further clinical trial with a larger number of patients and a better control should be done to finally verify it. 4. It is found that immunosupression do not seem to be related with the balance between pro- and anti-inflammatory cytokines, suggesting that the hypothesis of CARS should be further appraised.

Immunomodulatory agents for prophylaxis and therapy of infections.

The advent of the antibiotic era ushered in a shift towards non-pathogen-specific therapy of infectious diseases. This led to an overt emphasis on targeting microbial pathogens while strategies directed towards enhancing host immunity were neglected. In an effort to decrease sole reliance on antimicrobials, the time has come for a critical reappraisal of nonantibiotic, albeit immune response-enhancing substances. The diverse array of natural, synthetic, and recombinant immunomodulators discussed in this review succinctly demonstrate the potential of these agents to stimulate host defense mechanisms for prophylaxis and treatment of various microbial infections.

Review of thymic hormones in cancer diagnosis and treatment.

The thymus is an endocrine organ. A unified, physiological concept of humoral regulations of the immune response has emerged in the last three decades. The thymus is the major site of production of immunocompetent T lymphocytes from their hematopoietic stem cells. This complex process required direct cell to cell, receptor based interactions, as well as in situ paracrine information via the numerous cytokines and thymic hormones produced by the cells of thymic microenvironment. Thymic hormones induce in situ T-cell marker differentiation, expression and functions. These polypeptide hormones have also been shown by means of immunocytochemistry to localize in the reticulo-epithelial (RE) cells of the thymic cellular microenvironment. Due to the great complexity of the intrathymic maturation sequence of T lymphocytes and the diverse immunophenotypically unique subpopulations of T lymphocytes, it is quite unlikely that a single thymic humoral factor could control all of the molecular steps and cell populations involved. It is much more likely that an extremely rich and diverse, but genetically determined, milieu is present within the thymus, and that thus the control of intrathymic T lymphocyte maturation and the functional maturation of T cells involves the orchestral interaction of various thymic-specific factors and other molecules during the differentiation process. Thymosin fraction 5 and its constituent peptides influence several properties of lymphocytes including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, as well as the expression of various cell surface maturation/differentiation markers. Recently, derivatives of thymic hormones, mostly of thymosins, have been detected as products of neoplastically transformed cells and employed in the early diagnosis of neoplasms. In clinical trials, thymic hormones strengthen the effects of immunomodulators in immunodeficiencies, autoimmune diseases, and neoplastic malignancies. Combined chemo-immunotherapeutical anti-cancer treatment seems to be more efficacious than chemotherapy alone, and the significant hematopoietic toxicity associated with most chemotherapeutical clinical trials can be reduced significantly by the addition of immunotherapy.

Thymopentin and splenopentin as immunomodulators. Current status.

Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Arg-Lys-Asp-Val-Tyr) are synthetic immunomodulating peptides corresponding to the region 32-34 of a splenic product called splenin (SP) and the thymic hormone thymopoietin (TP), respectively. TP was originally isolated as a 5-kDa (49-amino acids) protein from bovine thymus while studying effects of the thymic extracts on neuromuscular transmission and was subsequently observed to affect T cell differentiation and function. TP I and II are two closely related polypeptides isolated from bovine thymus. A radioimmunoassay for TP revealed a crossreaction with a product found in spleen and lymph node. This product, named splenin, differs from TP only in position 34, aspartic acid for bovine TP and glutamic acid for bovine splenin and it was called TP III as well. Synthetic pentapeptides (TP-5) and (SP-5), reproduce the biological activities of TP and SP, respectively. It is now evident that various forms of TPs were created by proteolytic cleavage of larger proteins during isolation. cDNA clones have been isolated for three alternatively spliced mRNAs that encodes three distinct human T cell TPs. The immunomodulatory properties of TP, SP, TP-5, SP-5 and some of their synthetic analogs reported in the literature have been briefly reviewed.

Evaluation of clinical efficacy and tolerability of intravenous high dose thymopentin in advanced melanoma patients.

Thymopentin (TP5) has been recently evaluated as an immunotherapeutic agent for the treatment of cancer. Melanoma is a highly immunogenic malignancy, and in our previous studies the treatment of metastatic melanoma with TP5 showed encouraging results. In the present study, we evaluated the clinical efficacy and tolerability of high dose intravenous TP5 in 16 patients with melanoma which had metastasized to cutaneous and subcutaneous tissue. All patients were given 1 g intravenous TP5 every second day for 7 weeks and were then evaluated; responders were given a subsequent course of 2 g intravenous TP5 every second day for 5 weeks. Six patients showed a partial response after the first course and were given the second course: one patient achieved a complete response, while the other five remained in partial response at the end of the treatment. The mean duration of response was 7.5 months. No drug side effects were observed. Histopathological and immunohistochemical evaluation of regressing metastatic nodules showed the presence of tumour-infiltrating lymphocytes, necrosis, sclerosis, intratumoral vascular proliferation and microthrombosis. Immunophenotyping of lymphoid infiltrates demonstrated the prevalence of CD4+ and CD45RO+ T-lymphocytes in one patient. We conclude that high dose intravenous TP5 three times a week may induce a clinical response in patients with cutaneous and subcutaneous metastases of melanoma without relevant side effects.

Phase I-II study of dose intensified chemotherapy with filgrastim and thymopentin in patients with advanced cancer.

BACKGROUND: Carboplatin (CBDCA), cyclophosphamide (CTX) and etoposide (VP-16) combination chemotherapy is active in many tumors. A phase I-II study was designed in order to verify toxicity, maximum tolerated dose and activity of CBDCA, CTX and VP-16 given with Granulocyte Colony Stimulating Factor (G-CSF) and thymopentin (TP5), without bone marrow support. MATERIALS AND METHODS: A group of 12 heavily pretreated patients (PTS), 9 breast cancer, 2 small cell lung cancer and 1 gastric cancer, received fourteen courses of the described combination chemotherapy. Previous treatments were as follows: surgery in 10 PTS, radiotherapy in 7 PTS, chemotherapy in all PTS (median of 9 courses per patient). CBDCA, CTX, VP-16 were given over 3 days. CBDCA doses were calculated and expressed with the area under the concentration versus time curve (AUC). The dose range were as follows: CBDCA AUC 5.5-11 (400-800 mg/m2), CTX 1500-2500 mg/m2, VP-16 450-550 mg/m2, G-CSF was given 5 mg/kg/day from day 4 to day 17. TP5 was given, on alternate days, 1 mg/ kg from day 4 to day 30. RESULTS: 6 PTS developed fever > 38 degrees C for a median (M) duration of 4 days. 4 PTS required platelet support (M of 12 units) and 3 PTS red blood cells support (M of 2 units). Maximum tolerated dose was CBDCA AUC of 8, CTX 2000 mg/m2 and VP16500 mg/m2. No treatment related death occurred. Ten patients had responses and two had disease stabilisation. At the present time 5 PTS are alive and median overall survival is 13 months. CONCLUSIONS: These data indicate that dose intensified CT with the support of G-CSF and TP5 may be delivered safely and shows activity in heavily pre-treated patients.

Synthetic thymic fraction 5: effects of high dose administration on circulating lymphocytes in patients.

The synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr; TP-5) corresponding to the active site of the hormone thymopoietin, was given at the dose of 300 mg/m2/day (1 day), higher than the usually administered, to a group of 27 immunodepressed patients in order to determine the tolerability and the immunomodulatory activity. The examination of a series of hematological parameters including counts of differential clustering of lymphocytes by cytofluorimetric analysis was performed 24 hr and 48 hr after treatment, and repeated at different intervals up to 14 days after treatment. TP-5 caused a significant increase of circulating lymphocytes and particularly of CD3+CD4+ and CD3+CD8+ subtypes, peaking at 48 hr and maintaining the increased values up to the last examination on day 14 from treatment. A faster increase (zenith at 24 hr) was observed for CD4+ cells, in comparison with CD8+ cells (zenith at 48 hr). The number of patients that increased total lymphocytes or lymphocyte subset after treatment ranged between 52.6 (CD4+ cells) and 69.2% (NK cells), whereas about 7.7% (NK cells) to 36.9% (CD4+ cells) remained unchanged and a smaller amount of 10.5% (CD4+ and CD8+ cells) or 23.1% (NK cells) showed a decrease greater than 10% of their respective basal value. No significant relationship between responders and non-responders can be found on the basis of previous treatments, cancer type, sex or age.

New products? What new products?

AIDS: The New Products Committee of the PWA Health Group examined several products to determine whether the products should be made available through their buyers' club. Cat's Claw is popular because of the anecdotal data that it is a strong antiviral, antioxidant, anti-tumor and anti-inflammatory substance. However, the manufacturer would not supply any information that it is effective in AIDS treatment, and it was rejected. Thymopentin, which is being studied in the United States and is available commercially in Germany, was found to be effective in reducing the number of opportunistic infections in persons taking AZT, and was approved. Cantharadin was approved for treatment of Molluscum Contagiosum and will be provided to patients with a prescription for it. Nitazoxanide (NTZ) is a promising treatment for cryptosporidia and microsporidia, but is apparently not for sale anywhere in the United States.^ieng

Biological activity and clinical efficacy of intravenous high-dose thymopentin in metastatic melanoma patients.

Eight patients with cutaneous metastatic melanoma were submitted to high-dose intravenous thymopentin (TP5) treatment for 5 weeks: three patients received 1 g three times a week, three received 1 g daily and two received 2 g daily. Four out of eight patients presented a partial response of cutaneous lesions lasting for 1-7 months, and six remain alive with evidence of disease after a follow-up of 2-7 months. A remarkable histologic observation is the presence of tumour necrosis, which was seen as both single cells and large confluent areas. The majority of lymphoid cells present in the tumour are CD45RO+ and CD4+. The CD4+ cells might play an important role in the anti-tumour immune local response by secreting cytokines and inducing apoptotic and necrotic cell death. This hypothesis seems to be confirmed by the presence of a high number of CD4+ cells around intratumoral vessels, while the presence of endovascular micro-thrombosis provides indirect evidence of cytokine activity. Cellular lysis may be produced by the activity of both CD8+ and CD4+ lymphoid cells. The role of TP5 may be an activation of CD4+ and CD8+ lymphoid cells. Clinical and pathological data indicate that TP5 is able to produce consistent clinical and immunological effects in melanoma patients with cutaneous metastases.

Experimental therapies in the treatment of cutaneous T-cell lymphoma.

Although meaningful clinical responses have been demonstrated in cutaneous T-cell lymphoma using a number of therapeutic modalities, survival benefits have not been demonstrated for the majority of patients. Several novel therapies, including retinoids, purine analogs, biologic response modifiers, monoclonal antibodies, and fusion toxins have demonstrated activity and clinical promise in early studies.

[Evaluation of the treatment with thymopentin associated with radiotherapy in head and neck tumors]. / Valutazione del trattamento con timopentina associato alla radioterapia nei tumori della testa e del collo.

The aims of the study has been the analysis of the optimal conditions for the use of thymopentin in reducing the incidence and severity of early and late complications following radiotherapy of patients with head and neck cancers submitted to radiotherapy by means of cobalt or linear accelerator. 168 patients of 10 Center have been examined. Analysis of the results demonstrated that the tymopentin reduce the incidence and severe reactions (p < 0.05) in statistically significant manner in cases of irradiation of the hypopharynx, oropharynx in oral cavity. The complications were more frequent during cobalt beam therapy (p < 0.01) and the beneficial effect of the immunomodulating treatment were greater for females than the males (p < 0.05).