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Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study

, : Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study. Investigational New Drugs 12(2): 111-119

Gemcitabine (GEM) is a novel deoxycytidine analogue which has shown promising antitumor activity in solid tumor models and a broad range of schedule-dependent MTDs (12-4560 mg/m-2) in preliminary clinical studies. The present phase I trial evaluated escalating doses of weekly GEM using a 30-min infusion at a starting dose-level of 300 mg/m-2/wk times 3 every 28 days. At least 3 patients entered each dose-level step and 3 more cases were treated when significant toxicity was seen. A total of 39 patients with various advanced solid tumors and prior chemotherapy entered this study. Six escalation steps (102 courses) were tested to define the MTD at 1,370 mg/m-2/wk. No definite dose-effect relationships were observed for myelosuppression up to 1,095 mg/m-2 /wk. However, increased severity of leucopenia (dose-limiting,) and greater non-hematologic toxicity as well as a higher number of toxic treatment delays, requiring subsequent dose attenuation in 6 out of 12 patients, were observed at 1,370 mg/ m-2/wk. In all, 6 out of II patients experiencing WHO grade gtoreq 3 toxicity (11/21 events recorded in 11/18 courses) were treated at the MTD. Clinically significant toxicity included (patients with WHO grade 2-3): leucopenia (44%), thrombocytopenia (26%), anemia (23%), fever (69%), emesis (38%) and AST/ALT rise (26%). Mild proteinuria, ankle edema, skin rash, hair loss and mucositis were seen in ltoreq 5%. The good tolerability and the evidence of antitumor activity of GEM at doses gtoreq 875 mg/m-2/wk (1 CR and 3 PRs in 15 bladder cancer patients) encourage further phase II studies at much higher dose-levels (1,370 mg/m-2) than previously suggested.


PMID: 7860227

Other references

Beck Sickinger, A.G.; Wieland, H.A.; Wittneben, H.; Willim, K.D.eter; Rudolf, K.; Jung, G., 1994: Complete L-alanine scan of neuropeptide Y reveals ligands binding to Y-1 and Y-2 receptors with distinguished conformations. The synthesis of more than fifty 36-residue oligopeptide analogs of neuropeptide Y (NPY) and their affinity to human Y-1 and Y-2 receptors is described. Each amino acid of the natural sequence was replaced by L-alanine, the four alanine residues a...

Heckerling, P.S.; Verp, M.S., 1994: A cost-effectiveness analysis of amniocentesis and chorionic villus sampling for prenatal genetic testing. Amniocentesis and chorionic villus sampling are tests for the prenatal diagnosis of cytogenetic abnormalities. We calculated the incremental costs per abnormal birth averted, and the incremental costs per quality-adjusted outcome, of amniocentesis...

Nejgebauer, V., 1962: Moisture-retaining capacity of chernozems of the Backa region & the moisture constants characterizing them.. The moisture-retaining capacities of 2 deep chernozems on loess were high. In the top 200cm the average absolute moisture-retaining capacity determined by Kopecky's method & the moisture-retaining capacity determined by Gracanin's method...

Ligterink; Bakker, 1995: Renormalization of light-front Hamiltonian field theory. Physical Review. D, Particles and Fields 52(10): 5917-5925

Lezhava, T.; Jokhadze, T., 2007: Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals. The functional characteristics of chromosomes (level of total heterochromatin, chromosome instability, and sister chromatid exchanges [SCEs]) were studied in cultured lymphocytes derived from 80- to 91-year-old and 18- to 30-year-old (control grou...

Chakraverti, J., 2012: Operations for retroverted uterus. Journal. Obstetric and Gynaecological Society of Northern India 7(9): 150-150

Hubert, E.G.; Kalmanson, G.M.; Guze, L.B., 1963: Preservation Of Antigen-Coated Sheep Erythrocytes By Freezing For Use In Indirect Hemagglutination Procedure. Hubert, Earl G. (Veterans Administration Center, Los Angeles, Calif.), George M. Kalmanson, and Lucien B. Guze. Preservation of antigen-coated sheep erythrocytes by freezing for use in indirect hemagglutination procedure. J. Bacteriol. 86:569-572....

Song, H.; Yang, M.; Guo, H., 2016: Communication: Equivalence between symmetric and antisymmetric stretching modes of NH 3 in promoting H + NH 3 → H 2 + NH 2 reaction. NlmCategory="UNASSIGNED">Vibrational excitations of reactants sometimes promote reactions more effectively than the same amount of translational energy. Such mode specificity provides insights into the transition-state modulation of r...

Mraz, C., 1975: Do big queens mean big honey crops?. Gleanings in bee culture: 103 (2) 39-40

Janssen, George, 1929: The relationship of organic root reserves and other factors to the permanency of alfalfa stands. There is a rapid reduction in alfalfa stand after the 2nd yr. of cropping on the same land. Some varieties are more persistent in maintaining a good stand than others. Northern varieties of alfalfa seem to maintain their stand longer than southern...