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      Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a Phase II, randomized study

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          To evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy.

          Patients and methods

          Patients with SCLC (n = 164) were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m 2 intravenously on day 1, ifosfamide 3.5 mg/m 2 intravenously on day 1, and etoposide 200 mg/m 2 total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells.


          Differences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan–Meier analysis disclosed a survival benefit for group B ( P , 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P , 0.05).


          Among cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.

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          Most cited references 28

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          Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial.

          Postsurgical recurrence of hepatocellular carcinoma (HCC) is frequent and fatal. Adoptive immunotherapy is active against HCC. We assessed whether postoperative immunotherapy could lower the frequency of recurrence. Between 1992 and 1995, we did a randomised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy (n=76) or no adjuvant treatment (n=74). Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months. Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat. 76 patients received 370 (97%) of 380 scheduled lymphocyte infusions (mean cell number per patient 7.1x10(10) [SD 2.1]; CD3 and HLA-DR cells 78% [16]), and none had grade 3 or 4 adverse events. After a median follow-up of 4.4 years (range 0.2-6.7), adoptive immunotherapy decreased the frequency of recurrence by 18% compared with controls (45 [59%] vs 57 [77%]) [corrected] patients. Time to first recurrence in the immunotherapy group was significantly longer than that in the control group (48% [37-59] vs 33% [22-43] at 3 years, 38% [22-54] vs 22% [11-34] at 5 years; p=0.008). The immunotherapy group had significantly longer recurrence-free survival (p=0.01) and disease-specific survival (p=0.04) than the control group. Overall survival did not differ significantly between groups (p=0.09). Adoptive immunotherapy is a safe, feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC.
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            Angiogenic factors.

            Within the past 2 years, several angiogenic factors have been fully purified, their amino acid sequences determined, and their genes cloned. These polypeptides include acidic and basic fibroblast growth factor, angiogenin, and transforming growth factors alpha and beta. Other less well characterized angiogenesis factors have also been isolated, some of which are lipids. This article traces the discovery of the angiogenic factors and describes their possible significance in understanding growth regulation of the vascular system. When evaluated according to their putative targets, they appear to fall into two groups: those that act directly on vascular endothelial cells to stimulate locomotion or mitosis, and those that act indirectly by mobilizing host cells (for example, macrophages) to release endothelial growth factors. In addition to their presence in tumors undergoing neovascularization, the same angiogenic peptides are found in many normal tissues where neovascularization is not occurring. This suggests that physiological expression of angiogenic factors is tightly regulated. In addition to the persistent angiogenesis induced by tumors, it now appears that a variety of nonneoplastic diseases, previously thought to be unrelated, can be considered as "angiogenic diseases" because they are dominated by the pathologic growth of capillary blood vessels.
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              Cancer statistics for African Americans, 2013.

              In this article, the American Cancer Society estimates the number of new cancer cases and deaths for African Americans and compiles the most recent data on cancer incidence, mortality, survival, and screening prevalence based upon incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. It is estimated that 176,620 new cases of cancer and 64,880 deaths will occur among African Americans in 2013. From 2000 to 2009, the overall cancer death rate among males declined faster among African Americans than whites (2.4% vs 1.7% per year), but among females, the rate of decline was similar (1.5% vs 1.4% per year, respectively). The decrease in cancer death rates among African American males was the largest of any racial or ethnic group. The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of nearly 200,000 deaths from cancer among African Americans. Five-year relative survival is lower for African Americans than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Overall, progress in reducing cancer death rates has been made, although more can and should be done to accelerate this progress through ensuring equitable access to cancer prevention, early detection, and state-of-the-art treatments. Copyright © 2013 American Cancer Society, Inc.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                23 July 2013
                : 7
                : 611-617
                [1 ]Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
                [2 ]Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany
                [3 ]Thoracic Surgery Department, “Saint Luke” Private Hospital, Panorama, Thessaloniki, Greece
                [4 ]Immunology Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
                [5 ]Ear, Nose and Throat Department, “Saint Luke” Private Hospital, Panorama, Thessaloniki, Greece
                [6 ]Respiratory Diseases Department, Shanghai hospital, Second Military Medical University, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Paul Zarogoulidis Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki Exohi 1100, Greece 57010, Tel +30 231 099 2432, Fax +30 231 099 2433, Email pzarog@ 123456hotmail.com
                © 2013 Zarogoulidis et al, publisher and licensee Dove Medical Press Ltd

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Original Research

                Pharmacology & Pharmaceutical medicine

                immunomodifiers, lung cancer, sclc, interferon


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