Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Dec 2003
Randomized Controlled Trial Clinical TrialTwo different schedules of irinotecan (CPT-11) in patients with advanced colorectal carcinoma relapsing after a 5-fluorouracil and leucovorin combination. A randomized study.
To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy. ⋯ . The present study indicates that, in patients with ACC who have relapsed after 5-FU plus LV, the administration of irinotecan fractionated into two doses every 21 days yields a similar efficacy to, but a much lower incidence of toxicity than, the same total dose of irinotecan administered once every 21 days.
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Cancer Chemother. Pharmacol. · Dec 2003
Multicenter Study Comparative Study Clinical TrialPharmacokinetics of temozolomide given three times a day in pediatric and adult patients.
To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. ⋯ No difference appears to exist between pharmacokinetic parameters in adults and children when TMZ is administered in three doses daily. Hematologic toxicity was not related to TMZ AUC. AUC measurement does not appear to be of any use in optimizing TMZ treatment.
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Cancer Chemother. Pharmacol. · Dec 2003
Complementary antineoplastic activity of the cytosine nucleoside analogues troxacitabine (Troxatyl) and cytarabine in human leukemia cells.
Troxacitabine (BCH-4556, l-(-)-OddC, Troxatyl) is a novel beta- l-nucleoside analogue with potent antineoplastic activity both in vitro and in several tumor models in vivo, and is presently in phase II clinical trials. The combination of the cytosine analogues troxacitabine and araC (1-beta- d-arabinofuranosylcytosine, cytarabine) has shown promising activity in patients with acute myelogenous leukemia. To further examine the interactions between these two analogues, we investigated the in vitro and in vivo effects of their combination against a human leukemia cell line, CCRF-CEM. ⋯ Overall, our results show that the antileukemic activity of troxacitabine and araC is complementary when the two nucleoside analogues are combined in vivo. These effects appear to be related to their interaction at the level of DNA repair rather than to pharmacokinetic interactions. These results encourage the use of troxacitabine and araC in combination in patients with acute leukemia.
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Cancer Chemother. Pharmacol. · Nov 2003
Induction of TNF-alpha, uPA, IL-8 and MCP-1 by doxorubicin in human lung carcinoma cells.
We have previously demonstrated doxorubicin-induced urokinase (uPA) and interleukin-8 (IL-8) expression in human H69 small-cell lung carcinoma (SCLC) cells by a microarray technique using Human Cancer Chip version 2, in which 425 human "cancer-related" genes are spotted on the plates. The microarray analysis also revealed a significant induction of tumor necrosis factor-alpha (TNF-alpha), and doxorubicin-induced macrophage chemoattractant protein-1 (MCP-1) expression was demonstrated by an RNase protection assay. We extended the study by testing the effects of doxorubicin on the induction of TNF-alpha, uPA, IL-8 and MCP-1 in other types of lung carcinoma cells. ⋯ TNF-alpha, uPA, IL-8 and MCP-1 induced and secreted from tumor cells upon doxorubicin stimulation may activate surrounding cells expressing the receptors such as neutrophils and monocytes/macrophages in a paracrine fashion. TNF-alpha is a major proinflammatory cytokine, and IL-8 and MCP-1 are major chemoattractants for neutrophils and monocytes/macrophages, respectively. Furthermore, uPA activates matrix metalloproteinase 9 which can truncate and activate IL-8. Thus, the simultaneous induction of TNF-alpha, uPA, IL-8 and MCP-1 may enhance the interaction between tumor and inflammatory/immune cells, and augment cytotoxicity.
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Cancer Chemother. Pharmacol. · Nov 2003
Pharmacokinetics and tissue distribution of intraperitoneal paclitaxel with different carrier solutions.
For cancers that have disseminated to peritoneal surfaces, intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. Using a rat model we compared the pharmacokinetics and tissue absorption of paclitaxel infused intraperitoneally in two isotonic carrier solutions: 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution. ⋯ The use of intraperitoneal paclitaxel with hetastarch carrier solution provides a pharmacologic advantage for a local-regional killing of residual tumor cells with decreased systemic toxicity. Clinical investigations into the use of 6% hetastarch with high molecular weight chemotherapeutic agents are warranted.