Clin Cancer Res
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This phase II study was undertaken to assess objective response and toxicity of histone deacetylase inhibitor depsipeptide in patients with neuroendocrine tumors. ⋯ Depsipeptide was associated with a high number of potentially serious cardiac adverse events in patients with metastatic neuroendocrine tumor. As sudden death possibly associated with depsipeptide was observed in this trial, the risks for potentially life-threatening arrhythmia associated with this agent need to be comprehensively evaluated.
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Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non-small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib. ⋯ Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors.
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Ewing tumor cell survival and proliferation depends on several autocrine loops. Targeting these loops is a promising therapeutic approach. We recently showed the cytostatic role of imatinib, an inhibitor of the SCF-KIT loop, on Ewing tumor cells, and in this study, we intend to analyze the inhibition of the insulin-like growth factor I receptor (IGF1R) loop. ⋯ Inhibition of Ewing tumor cell proliferation by ADW742 is mediated through blockade of IGF1R signaling. Combination of ADW742 with imatinib, vincristine, and doxorubicin induces a significant reduction of tumor cell growth, mainly by the increase in apoptosis with a pattern depending on IGF1R activation levels. This study supports a potential role for ADW742 in the treatment of Ewing tumor and AKT/mTOR as a possible surrogate marker of response to therapy.
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To evaluate the efficacy and toxicity of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 for patients with advanced or recurrent gastric cancer. ⋯ Docetaxel/S-1 combination is highly active and well tolerated in advanced or recurrent gastric cancer. Further investigation in randomized studies is warranted.
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The major limitation to successful chemotherapy of neuroblastoma is the toxicity of traditional antitumor drugs. Hence, less toxic and more effective drugs are to be found, and novel formulations of conventional compounds allowing a more favorable biodistribution should be sought for. In an attempt to pursue this task, we recently synthesized an amphiphilic polymer based on a polyvinyl alcohol backbone [P10(4)]. ⋯ Our data suggest that P10(4) holds promise as an anticancer compound and, because of its lack of interaction with DNA, is unlikely to give rise to drug resistance.