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

PURPOSE: 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. RESULTS: 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). CONCLUSION: 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.

Potential prognostic value of intracellular cytokine detection by flow cytometry in pulmonary sarcoidosis.

In pulmonary sarcoidosis, differential cytokine production in the lungs could be related to variable prognosis of patients at different stages of disease. Twenty patients with pulmonary sarcoidosis (10 at radiographic stage I and 10 at stages II-IV), as well as 10 age-matched healthy volunteers participated in the study. A 4-colour flow cytometric technique was used to measure interferon-γ (IFN-γ), interleukin (IL)-2, tumour necrosis factor-α (TNF-α), IL-4, and IL-13 production in phorbol myristate acetate (PMA)/ionomycin-stimulated CD4+ and CD8+ T cells from bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) of patients, and PB of control subjects. CD4+ T cells from patients showed higher expression of IFN-γ in BALF than in PB. Significant correlations were observed between the percentages of BALF CD4+ and CD8+ T cells expressing intracellular IFN-γ, IL-2, and TNF-α. Stage I patients had lower percentages of IFN-γ-producing CD4+ and CD8+ T cells, as well as TNF-α-producing CD8+ T cells, in BALF (but not in PB) than stage II-IV patients. A decreased TH1 and TC1 response was demonstrated in BALF of patients at stage I of disease, which could explain their anticipated better prognosis.

Randomized study of the effect of pentoxifylline or octreotide on serum levels of TNF-alpha and IL-6 after endoscopic retrograde cholangiopancreatography.

OBJECTIVES: To study the effect of pentoxifylline and octreotide administration on serum levels of TNF-alpha and IL-6, in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), whether they developed pancreatitis or not. METHODS: Out of 590 patients undergoing ERCP, 30 who developed pancreatitis and 25 who did not (controls) were enrolled. Pentoxifylline was given to 23 patients (15 with and eight without pancreatitis) and octreotide to 19 patients (nine with and 10 without pancreatitis, respectively). Thirteen patients did not receive any preventive medication (six with and seven without pancreatitis, respectively). Blood samples were collected at baseline, 6 and 24 h after ERCP. RESULTS: IL-6 increased significantly in patients with pancreatitis at the 6 h (4.2 pg/ml SD: 5.8) and at the 24 h (6.6 pg/ml SD: 9.8) compared with patients without pancreatitis at the 6 h (2.1 pg/ml SD: 3.6) and 24 h (1.9 pg/ml SD: 2.5) (P < 0.01). No significant difference in the values of TNF-alpha and IL-6 obtained among the three study groups in patients with or without pancreatitis was observed. TNF-alpha levels at the 24 h were lower than baseline in patients with pancreatitis who received octreotide (P = 0.04). CONCLUSION: IL-6 increased in the first 24 h of post-ERCP pancreatitis. Pentoxifylline and octreotide cannot prevent IL-6 elevation but octreotide reduces TNF-alpha levels, which may have an impact on the severity of post-ERCP pancreatitis.

Colchicine treatment of liver fibrosis.

BACKGROUND/AIMS: Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. The results from clinical trials have however been inconsistent. The aim of the present study was to evaluate the effect of colchicine in the treatment of patients with hepatic fibrosis of various etiologies. METHODOLOGY: Thirty-eight patients were randomized to receive either colchicine 1 mg per day (n=21, group A) or no antifibrotic agent (n=17, group B). Treatment lasted for at least 12 months. Liver biopsy was performed prior to entry and after 12 months. Liver function tests, serum aminoterminal peptide of procollagen III (PIIINP) levels and CD4:CD8 ratio of peripheral blood T lymphocytes (PBTLs) were performed at baseline and bimonthly or every 4 months post-treatment. RESULTS: Mean albumin serum levels increased 12 months post-treatment period only in group A (p<0.05). Mean serum PIIINP levels did not change significantly after 12 months of treatment in group A; in 7 patients a reduction in mean serum PIIINP levels was noticed during 24-month post-treatment follow-up period (p<0.05). At baseline, a correlation between focal or bridging necrosis and CD4:CD8 ratio of PBTLs was noticed in group A (p < 0.05). The mean serum CD4:CD8 ratio was increased after 12 months of colchicine treatment (p<0.05) associated with abrogation of this correlation; comparison between the two groups revealed increased CD4:CD8 ratio in group A at 12 months (p<0.05). The histological findings according to Knodell criteria in both groups remained unchanged after 12 months follow-up. The treatment was well tolerated in all patients. CONCLUSIONS: Long-term colchicine treatment in patients with hepatic fibrosis appears to exert an anti-inflammatory, anti-fibrotic and immunomodulatory effect.