thymosin and Carcinoma--Small-Cell

Using a partially purified preparation, thymosin fraction 5, we have documented that thymosin can correct many of the immunological deficiencies resulting from the lack of thymosin function in animal models and in humans. Ongoing studies indicate that there is a family of biologically active peptides within fraction 5 that act on T-cell subpopulations to maintain normal immunological reactivity. Several of these peptides have been purified to homogeneity. Two peptides, thymosin alpha 1 and beta 4, have been sequenced and chemically synthesized. Thymosin fraction 5 has been used in most clinical trials reported to date, including children with immunodeficiency disease and patients with autoimmune diseases and cancer. Most recently, the National Cancer Institute has initiated a number of Phase I and Phase II clinical trials with thymosin fraction 5 and synthetic alpha 1 as part of a new Biological Response Modifier Program. Preliminary results from two of these studies look encouraging.

Topics: Amino Acid Sequence; Animals; Autoimmune Diseases; Carcinoma, Small Cell; Cattle; Clinical Trials as Topic; Isoelectric Focusing; Lung Neoplasms; Macrophage Migration-Inhibitory Factors; Molecular Weight; Peptides; T-Lymphocytes; T-Lymphocytes, Regulatory; Terminology as Topic; Thymalfasin; Thymosin

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.

Topics: Carcinoma, Small Cell; Clinical Trials as Topic; Combined Modality Therapy; Humans; Lung Neoplasms; Radiotherapy; Random Allocation; Thymosin; Time Factors

From June 1979 through April 1982, we treated 35 patients with limited small cell carcinoma on an intensive chemo-radio-immunotherapy regimen, consisting of induction with cyclophosphamide, doxorubicin, and vincristine, alternately cycled with VP-16 and cisplatin. Patients were stratified by performance status and randomized to thymosin, fraction V, or no thymosin. Induction was followed by consolidation, consisting of prophylactic whole-brain radiotherapy and multifield radiotherapy to the primary and mediastinum with cyclophosphamide and vincristine. Patients who were complete responders (CRs) postconsolidation resumed maintenance immediately. Patients were followed from 1 to 3.8 years (median, 2.2 years) at the time of analysis. After induction, 35% (12/34) had become CRs; after consolidation radiotherapy, an additional 10/34 became CRs for a total CR rate of 65% (22/34). There were only 9/34 local failures (26%), of which all but one were impatients who had not become CRs. A prolonged median survival (21 months) has been obtained in patients with limited small cell carcinoma of lung treated with an intensive combined modality regimen. At 1 year, survival is 83%; at 2 years, 46%. There is a 33% long-term survival (greater than 3 years). There is no difference in survival or recurrence rate between patients treated with or without thymosin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Small Cell; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Prognosis; Radiotherapy Dosage; Thymosin; Tomography, X-Ray Computed

Using a partially purified preparation, thymosin fraction 5, we have documented that thymosin can correct many of the immunological deficiencies resulting from the lack of thymosin function in animal models and in humans. Ongoing studies indicate that there is a family of biologically active peptides within fraction 5 that act on T-cell subpopulations to maintain normal immunological reactivity. Several of these peptides have been purified to homogeneity. Two peptides, thymosin alpha 1 and beta 4, have been sequenced and chemically synthesized. Thymosin fraction 5 has been used in most clinical trials reported to date, including children with immunodeficiency disease and patients with autoimmune diseases and cancer. Most recently, the National Cancer Institute has initiated a number of Phase I and Phase II clinical trials with thymosin fraction 5 and synthetic alpha 1 as part of a new Biological Response Modifier Program. Preliminary results from two of these studies look encouraging.

Topics: Amino Acid Sequence; Animals; Autoimmune Diseases; Carcinoma, Small Cell; Cattle; Clinical Trials as Topic; Isoelectric Focusing; Lung Neoplasms; Macrophage Migration-Inhibitory Factors; Molecular Weight; Peptides; T-Lymphocytes; T-Lymphocytes, Regulatory; Terminology as Topic; Thymalfasin; Thymosin

Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.

Topics: Antineoplastic Agents; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Etoposide; Female; Humans; Ifosfamide; Lomustine; Lung Neoplasms; Male; Methotrexate; Procarbazine; Thymosin; Thymus Hormones; Vincristine

Studies on the effect of thymosin on T-cell levels in vitro among normal persons and cancer patients show that, in general, T-cell levels increase after incubation with thymosin in populations with low initial T-cell levels while the levels decrease in populations with high initial T-cell levels. In patients with small cell carcinoma of the lung receiving intensive chemotherapy also randomized to receive thymosin at a dose of 60 mg/m2, thymosin at a dose of 20 mg/m2, or placebo twice weekly, increased survival occurred in patients receiving the thymosin dose of 60 mg/m2. The increase in survival was greatest in patients with low pretreatment T-cell and alpha2HS-glycoprotein levels. These observations suggest that the cancer patients most likely to benefit therapeutically from adjuvant treatment with thymosin are those with relatively low initial T-cell levels and other parameters of cellular immunity.

Topics: Carcinoma, Small Cell; Clinical Trials as Topic; Glycoproteins; Humans; Immunity, Cellular; In Vitro Techniques; Leukocyte Count; Lung Neoplasms; T-Lymphocytes; Thymosin; Thymus Hormones

Prothymosin-alpha, the precursor of thymosin-alpha1, may play a role in cell proliferation, and the plasma level of thymosin-alpha1 may reflect the degree of proliferation of the tumor cells.. Recently, a new sandwich immunoradiometric assay for thymosin-alpha1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-alpha1 in 131 lung cancer patients.. We found that the mean plasma thymosin-alpha1 levels in lung cancer patients were higher than in normal individuals (P < 0.001). However, half of the patients showed normal levels. Thymosin-alpha1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-alpha1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P = 0.03). Survival of patients with normal levels of plasma thymosin-alpha1 was significantly better than that with higher levels (P = 0.04).. The plasma level of thymosin-alpha1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Division; Female; Humans; Immunoradiometric Assay; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Thymalfasin; Thymosin

Topics: Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Line; Humans; Immune Sera; Lung Neoplasms; Radioimmunoassay; Sensitivity and Specificity; Thymalfasin; Thymosin; Tumor Cells, Cultured

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.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Predictive Value of Tests; Radiotherapy; Risk Factors; Survival Rate; Thymosin

The prognostic implications of cigarette smoking were investigated in 112 patients with small cell lung cancer. Twenty had stopped smoking permanently before diagnosis (NS-Prior), 35 had stopped at diagnosis (NS-Dx), and 57 patients continued smoking (S). Therapies included chemotherapy alone or with radiation therapy, with or without thymosin fraction V. The survival difference among the three groups was statistically significant. The NS-Prior patients had the best survival, followed by NS-Dx patients and finally S patients. No S patient has survived, disease free, more than 96 weeks, while three NS-Prior and three NS-Dx patients are disease free 103 to 220 weeks after start of treatment. Thymosin, 60 mg/sq m, yielded survival benefits for the S group only. Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation of smoking, even at diagnosis, may have beneficial effects on survival.

Topics: Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Etoposide; Humans; Lung Neoplasms; Prognosis; Smoking; Thymosin; Vincristine

Topics: Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Glycoproteins; Humans; Immunity, Cellular; Leukocyte Count; Lung Neoplasms; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Carcinoma, Small Cell; Humans; Immunity, Cellular; Leukocyte Count; Lung Neoplasms; T-Lymphocytes; Thymosin; Thymus Hormones