Anti-cancer drugs
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Randomized Controlled Trial Clinical Trial
A small randomized phase III single-center trial on postoperative UFT administration in patients with completely resected non-small cell lung cancer.
Our objective was to clarify the efficacy of UFT administration after the complete resection of non-small cell lung cancer (NSCLC) at a single-center institution, avoiding the biases produced by interinstitutional differences. A total of 30 patients who underwent the complete resection of NSCLC at our hospital between 1987 and 2001 were randomly assigned to a control group or to a UFT group (400 mg/day for 2 years). Thirteen patients were assigned to the control group and 17 patients were assigned to the UFT group. ⋯ Two patients suffered a relapse in the UFT group, but the relapse occurred after the discontinuation of UFT administration. We conclude that the administration of UFT as an adjuvant therapy prolonged the overall survival and disease-free survival rates of patients after the resection of NSCLC in a small study performed at a single institution. Interinstitutional differences, particularly operating procedures, should be carefully considered when performing large multicenter clinical studies.
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Clinical Trial
Semi-extended, six weekly rituximab infusions in pre-treated advanced low-grade B cell non-Hodgkin's lymphoma: a phase II study.
Either four or eight weekly rituximab infusions in relapsed or refractory low-grade or follicular B cell non-Hodgkin's lymphoma (NHL) are well tolerated and efficacious. This phase II trial investigated the safety and efficacy of six weekly rituximab doses in chemotherapeutically pre-treated relapsed or refractory low-grade NHL patients. Sixty-eight patients (median age 64 years) received six i.v. rituximab infusions 375 mg/m2 weekly. ⋯ Median time to progression for all patients was 14 months and for responders 21 months. More than half the 42 patients evaluated for efficacy and more than 70% of the 25 responding patients still survived longer than 3 years after treatment. The safety profile and efficacy achieved in this study compare favorably with those seen with four or eight weekly doses in pre-treated low-grade NHL.
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Comparative Study
Imatinib mesylate (STI571; Glivec)--a new approach in the treatment of biliary tract cancer?
Non-resectable biliary tract cancer is associated with poor prognosis due to widespread resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to explore new therapeutic approaches like the inhibition of tyrosine kinases. The aim of this study was to determine the expression of c-kit and platelet-derived growth factor (PDGF) receptors (PDGFRs) and the effects of the tyrosine kinase inhibitor imatinib +/- 5-fluorouracil (5-FU) on proliferation and apoptosis in biliary tract cancer cell lines. ⋯ The combination with 5-FU increased the effect of imatinib mesylate in all cell lines. Treatment of cells with imatinib +/- 5-FU was associated with a significant induction of apoptosis, but no inhibition of proliferation. We conclude that imatinib alone exerts marked effects on c-kit+ biliary tract cancer cell lines only at intermediate and high concentrations, but there is a potential role of low-dose imatinib in combination with 5-FU for the treatment of biliary tract cancers.
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Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) is studied in a phase I study in the treatment of malignant pleural mesothelioma and pleural thymoma. We studied the pharmacokinetics of doxorubicin and cisplatin used during the HITHOC procedure. Furthermore, the penetration characteristics of doxorubicin were examined. ⋯ No leukopenia or hair loss was seen. Doxorubicin penetrated into the intercostal muscle specimen, albeit that there was considerable variation in distribution throughout the specimen. We conclude that HITHOC with doxorubicin and cisplatin is relatively a safe procedure with the advantage of high intrathoracic cytostatic drug concentrations, while having limited systemic side effects.
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Sulfasalazine (SASP) is a novel, potent inhibitor of cellular cystine uptake mediated by the x(c)- cystine/glutamate antiporter. Lymphoid cells cannot synthesize cyst(e)ine and depend for growth on its uptake from their micro-environment. We previously showed that SASP (0.2 mM) can abrogate lymphoma cell proliferation in vitro by specifically inhibiting x(c)- -mediated cystine uptake. ⋯ Addition of 2-mercapto-ethanol (60 microM), a cystine uptake enhancer, almost completely prevented this growth arrest, indicating that SASP specifically inhibited cysteine secretion by the fibroblasts, a process based on x(c)- -mediated cystine uptake. It is proposed that the lymphoma growth-inhibitory activity of SASP in vivo involves inhibition of cysteine secretion by tumor-associated somatic cells (macrophages, dendritic cells), leading to cysteine starvation of the tumor cells and apoptosis. The difference between the lymphoma cells and fibroblasts in sensitivity to SASP treatment is consistent with the marked antitumor effect of SASP lacking significant side effects.