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

• Published in: Drug design, development and therapy development and therapy, 2013-01, Vol.7 (default), p.611-617
• Main Authors: Zarogoulidis, Konstantinos, Ziogas, Eftimios, Boutsikou, Efimia, Zarogoulidis, Paul, Darwiche, Kaid, Kontakiotis, Theodoros, Tsakiridis, Kosmas, Porpodis, Konstantinos, Latsios, Dimitrios, Chatzizisi, Olga, Karapantzos, Ilias, Li, Qiang, Kyriazis, Georgios
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Cancer; Carboplatin; Care and treatment; CD3 antigen; CD4 antigen; CD8 antigen; Chemotherapy; Cytokines; Disease control; Drug therapy, Combination; Etoposide; Female; Health aspects; Humans; Ifosfamide; immunomodifiers; Immunotherapy; Interferon; Interferon-alpha - administration & dosage; Interferon-gamma - administration & dosage; Irradiation; Lung cancer; Lung cancer, Small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lymphocytes; Lymphocytes T; Male; Markers; Middle Aged; Natural killer cells; Neoplasms; Original Research; Patients; Radiation; SCLC; Small cell lung carcinoma; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - immunology; Small Cell Lung Carcinoma - mortality; Statistical analysis; Survival; α-Interferon; γ-Interferon
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S43184

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 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.