ABSTRACT
The liver is the most common anatomical site for hematogenous metastases from colorectal cancer. Therefore effective treatment of liver metastases is one of the most challenging elements in the management of colorectal cancer. However, there is rare available clinical consensus or guideline only focusing on colorectal liver metastases. After six rounds of discussion by 195 clinical experts of the Shanghai International Consensus Expert Group on Colorectal Liver Metastases (SINCE) from 29 countries or regions, the Shanghai Consensus has been finally completed, based on current research and expert experience. The consensus emphasized the principle of multidisciplinary team, provided detailed diagnosis approaches, and guided precise local and systemic treatments. This Shanghai Consensus might be of great significance to standardized diagnosis and treatment of colorectal liver metastases all over the world.
Subject(s)
Colorectal Neoplasms/pathology , Consensus , Liver Neoplasms/secondary , China/epidemiology , Humans , Incidence , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Neoplasm MetastasisABSTRACT
To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n = 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-α, interferon-γ) in supernatants of mixed-lymphocyte-culture and in serum (n = 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay. We correlated our data with lytic capabilities of stimulated T-cells in a fluorolysis-assay and clinical data: Dendritic-cell-/mononuclear-cell-stimulation of T-cells resulted in increased cytokine-levels in culture-medium compared to serum. There were no significant differences between cytokine-patterns of cases with/without lytic T-cell-activity, response to immunotherapy (stem cell transplantation/donor-lymphocyte-infusion) or graft-versus-host-disease. However, some predictive cytokine-cut-off-values for antileukaemic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease could be defined. Cytokine-profiles alone, without functional assays, are no useful tool to predict antileukaemic T-cell-function, although they can indicate lytic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease.
Subject(s)
Dendritic Cells/immunology , Immunotherapy , Leukemia, Myeloid, Acute/therapy , Lymphocyte Activation/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Child , Cytokines/metabolism , Cytotoxicity, Immunologic/immunology , Female , Humans , Immunotherapy/methods , Leukemia, Myeloid, Acute/immunology , Lymphocyte Culture Test, Mixed , Male , Middle Aged , Stem Cell Transplantation/methods , Young AdultABSTRACT
BACKGROUND: Preliminary data suggest that pegfilgrastim given on day 4 (P4) might be superior to pegfilgrastim on day 2 (P2) in reducing grade 4 leucopenia. METHODS: Patients with node-positive primary breast cancer receiving epirubicin-paclitaxel-cyclophosphamide chemotherapy were randomized to receive P2 versus P4. Primary endpoint was leucopenia grade 4, assuming a risk reduction of 50% with P4 from 50% in P2 to 25% with P4. RESULTS: Three-hundred fifty-one patients were randomized to P2 (n = 174) versus P4 (n = 177). The rate of leucopenia (grade 4) was 47.1% with P2 and 42.0% with P4 (p = 0.387), neutropenia (grade 3 + 4) was 47.9% versus 40.8% (p = 0.337), FN was 4.7% versus 8.0% (p = 0.271), and infections was 29.9% versus 25.4% (p = 0.404), respectively. CONCLUSION: This study failed to demonstrate that pegfilgrastim on day 4 was more efficacious than on day 2 with respect to grade 4 leucopenia (the primary endpoint), febrile neutropenia, or infections.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Leukopenia/prevention & control , Neutropenia/prevention & control , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Drug Administration Schedule , Epirubicin/administration & dosage , Female , Fever/prevention & control , Filgrastim , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Leukopenia/chemically induced , Middle Aged , Neutropenia/chemically induced , Paclitaxel/administration & dosage , Polyethylene Glycols , Prospective Studies , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Time Factors , Young AdultABSTRACT
BACKGROUND: Carcinomas of unknown primary (CUP) account for approximately 2-5% of all cancer diagnoses. Except for some subsets with favorable prognosis, for most of these patients treatment options are limited, and no standard first-line regimen has been identified. We performed a phase II study with oxaliplatin (OX) and capecitabine (CAP) as first-line treatment for patients with histo-or cytologically proven adeno- or undifferentiated CUP. PATIENTS AND METHODS: Protocol treatment in this multicenter trial consisted of CAP 1,000 mg/m(2) twice daily orally (days 1-14) and OX 130 mg/m(2) intravenously (day 1), repeated every 21 days at a maximum of 6 cycles. The primary endpoint was the response rate (RR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 51 patients with CUP (71% with poorly differentiated adenocarcinoma; 41% ECOG performance status (PS) 0, 39% PS 1, 10% PS 2, 55% with elevated lactate dehydrogenase (LDH), and 39% with liver metastases) were enrolled in this study. We observed an objective RR of 11.7% and a median PFS of 2.5 months as well as an OS of 7.5 months with a good toxicity profile. CONCLUSION: CAP/OX did not reach higher RR compared to a standard regimen with paclitaxel/carboplatin, which discourages further investigation of this schedule in CUP.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Neoplasms, Unknown Primary/drug therapy , Organoplatinum Compounds/administration & dosage , Adenocarcinoma/diagnosis , Adult , Aged , Capecitabine , Deoxycytidine/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasms, Unknown Primary/classification , Neoplasms, Unknown Primary/diagnosis , Oxaliplatin , Treatment OutcomeABSTRACT
Mortality in patients with advanced colorectal cancer(CRC) remains high. Epidemiologic studies show that individuals taking nonselective, nonsteroidal anti-inflammatory drugs, including aspirin, have a significant reduction in CRC mortality, compared with those not taking these agents. The recent characterization of cyclooxygenase- I and -2 (COX- I and COX-2) isoforms has led to an expanded understanding of how nonsteroidal anti-inflammatory drugs may help prevent polyp formation. Cyclooxygenase enzymes are required for the conversion of arachidonic acid to prostaglandins.COX-2 mediates the inflammatory effects of COX activity, is induced by a wide spectrum of growth factors and proinflammatory cytokines, and is overexpressed in numerous premalignant and malignant lesions, including CRC. Treatment with the selective COX-2 inhibitor celecoxib has shown promising results in the prevention of CRC, Numerous studies show that this COX-2 selective inhibitor is a potent suppressor of colon polyps both in animal models for familial adenomatous polyposis and in patients with this condition. This has led to the US Food and Drug Administration approval of celecoxib for the treatment of patients with familial adenomatous polyposis. The role of celecoxib in cancer treatment is still evolving. Recent studies have identified a potential benefit for adding celecoxib to standard CRC chemotherapy regimens to increase their efficacy and reduce their associated toxicity.