Paclitaxel and gemcitabine versus paclitaxel and vinorelbine in patients with advanced non-small-cell lung cancer. A phase III study of the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: Paclitaxel (Taxol) and vinorelbine have shown synergism of cytotoxic effects in vitro and clinical activity in phase I and II studies. This combination was compared prospectively with the paclitaxel/gemcitabine regimen in non-operable non-small-cell lung cancer. PATIENTS AND METHODS: Chemotherapy-naive patients, stage IIIbwet and IV with performance status (0-1), were randomized to receive paclitaxel 200 mg/m(2) on day 1 plus gemcitabine 1 gm/m(2) (group A) on days 1 and 8 every 3 weeks or paclitaxel 80 mg/m(2) plus vinorelbine 22.5 mg/m(2) (group B) on days 1, 8 and 15 every 4 weeks. RESULTS: A total of 398 out of 415 patients were eligible for analysis on intent-to-treat basis (group A: 196, group B: 202). Progression-free survival (PFS) was 5.0 months [95% confidence interval (CI) 4.3-5.6] and 4.4 months (95% CI 3.7-5.2) for groups A and B respectively (P=0.365). Median survival was 11.1 months (95% CI 9.2-13.0) and 8.6 months (95% CI 7.0-10.2) for groups A and B respectively (P = 0.147). Grade 3/4 neutropenia and leukopenia were worse in group B (P<0.001, in both cases). Febrile neutropenia and severe infections were more prominent (P<0.001, P=0.029 respectively) in group B. CONCLUSION: Although response rate, PFS and survival were non-different in both groups, toxicity was significantly worse in group B and therefore further investigation of P-Vin is of no value.

Circulating soluble E-cadherin levels are of prognostic significance in patients with multiple myeloma.

BACKGROUND: The epithelial transmembrane molecule E-cadherin (E-Cad) is the prime mediator of epithelial cell-cell adhesion, through homotypic interactions. It also participates in the maintenance of cytoskeletal structure and cell-cell signalling, while there are no published reports of expression of E-Cad in non-epithelial tissues. We examined whether the circulating levels of soluble E-Cad in newly diagnosed patients with multiple myeloma (MM) are of prognostic significance. PATIENTS AND METHODS: We used an ELISA method to determine the levels of circulating soluble E-cadherin (sE-Cad) in 21 newly diagnosed patients with MM and in 29 healthy volunteers, as a control group. RESULTS: MM patients demonstrated increased circulating levels of sE-Cad, compared with controls (p<0.0001). Increased circulating sE-Cad levels correlated with LDH levels at diagnosis (p<0.001) and poor prognosis. Multivariate analysis demonstrated that sE-Cad levels are an independent prognostic factor of survival (p<0.0207). CONCLUSION: Our data suggest that adhesion molecules play a role in the pathogenesis of MM, establish sE-Cad as an independent marker of survival and, finally, provide evidence of non-epithelial production of E-Cad in MM patients.

Prognostic significance of soluble adhesion molecules in Hodgkin's disease.

BACKGROUND: Cell adhesion may play a pivotal role in the development, progression and metastasis of solid malignancies. We evaluated the serum concentration of four adhesion molecules and their prognostic significance in patients with Hodgkin's Disease (HD). PATIENTS AND METHODS: Serum samples from 20 HD patients were collected at diagnosis, after 3 cycles of chemotherapy and at completion of treatment and compared with a control group of 29 apparently healthy subjects. Soluble forms of E-Selectin (sE-Selectin), ICAM-1 (sICAM-1), VCAM-1 (sVCAM-1) and E-Cadherin (sE-Cad) were measured by standard ELISA assays. RESULTS: Significantly increased serum levels of sICAM-1 and sE-Selectin were determined in HD patients at diagnosis compared to controls (p<0.0001), while sVCAM-1 at diagnosis correlated significantly with both sICAM-1 and sE-Selectin levels (r=0.5, p=0.03). Chemotherapy resulted in a significant decrease of sICAM-1 and sE-Selectin levels (p=0.02 and p=0.002, respectively). CONCLUSION: Serum levels of ICAM-1 and E-Selectin in newly diagnosed HD patients were found significantly increased, suggesting a possible involvement of these two molecules in the pathogenesis of the disease. Their rapid decrease following chemotherapy was found to be an independent predictor of response to treatment.

The prognostic role of CD5 negativity in B-cell chronic lymphocytic leukaemia: a case-control study.

B cells in chronic lymphocytic leukaemia (CLL) usually express the CD5 antigen, which appears to participate in the pathogenesis of autoimmune phenomena. However, 7-20% of B-CLL patients are CD5-. The aim of this study was to assess whether CD5 expression could be used as a discriminating factor for two subgroups of B-CLL. Twenty-nine CD5- B-CLL patients were compared in terms of clinico-biological characteristics and survival with a control group of 29 sex- and age-matched, consecutive CD5+ B-CLL subjects. B-CLL was considered to be CD5- when less than 5% of mononuclear cells expressed CD5 after subtraction of the number of T cells. Splenomegaly, lymph node involvement, and haemolytic anemia were found in CD5+ patients in a significantly higher proportion than in their CD5- counterparts, who presented with an earlier stage of disease. CD5- patients had a median survival of 97.2 (22-130) months, exceeding CD5+ subjects significantly [84.0 (19-120) months, p = 0.0025]. CD5- patients seemingly present with milder disease and have a favourable prognosis compared with the vast majority of B-CLL patients who express CD5.

Calcium and strontium metabolic studies in patients on CAPD.

BACKGROUND: Strontium is known to affect calcium metabolism both experimentally and in clinical studies on conditions other than end-stage renal failure (ESRF) and continuous ambulatory peritoneal dialysis (CAPD). OBJECTIVE: To investigate Sr metabolism in relation to that of Ca in ESRF patients undergoing CAPD, and the possible influence of the duration of treatment. DESIGN: Cross-sectional observational study. SETTING: University medical center and Institute of Nuclear Physics. PATIENTS: Twenty-four patients on CAPD; 14 chronic renal failure (CRF) patients not on dialysis, and 52 healthy controls. MEASUREMENTS: Calcium and Sr content of serum, urine or dialysate effluent, and selected dietary products. RESULTS: Calcium and Sr are absorbed by the intestinal tract of healthy subjects with equal efficiency. Serum Ca levels were considerably lower in CRF patients than in healthy subjects and patients on CAPD (p < 0.001). Serum Sr was significantly higher in both CAPD and CRF patients than in healthy controls (p < 0.001). The Sr/Ca ratio in the sera of the healthy subjects was defined by the preferential excretion of Sr over Ca by the kidney. This preferential excretion was lost during renal failure. During treatment there was a tendency for the uptake of both Ca and Sr to increase. CONCLUSIONS: Strontium is accumulated in the body during renal failure and CAPD cannot restore normal levels. Considering the varying effects of different doses of Sr on bone metabolism experimentally, it would be interesting to determine by further studies the possible significance of the observed Sr accumulation for renal bone disease.