Clin Cancer Res
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Bladder tumors develop through different molecular pathways. Recent reports suggest activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene as marker for the "papillary" pathway with good prognosis, in contrast to the more malignant "carcinoma in situ" (CIS) pathway. The aim of this clinical follow-up study was to investigate the role of FGFR3 mutations in bladder cancer development in a longitudinal study. ⋯ FGFR3 mutations seem to have a central role in the early development of papillary bladder tumors. These tumors follow a common molecular pathway, which is different from tumors with concomitant CIS. FGFR3 mutations do not seem to play a role in bladder cancer progression.
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To determine the maximal tolerated dose and dose-limiting toxicities (DLT) of pegamotecan (polyethylene glycol-camptothecin) in patients with advanced malignancies when administered in cycles of once weekly for 3 of 4 weeks. ⋯ The maximal tolerated dose of pegamotecan when administered weekly for 3 of 4 weeks is 3,240 mg/m(2). The DLT was neutropenia. Among nonhematologic toxicities, the incidence of gastrointestinal toxicity was low, but genitourinary toxicity seems to occur in the same effective dose range as noted with native camptothecin in earlier trials (27-43 mg/m(2)). The observed antitumor activity suggests that pegamotecan has single-agent activity and merits further investigation in phase 2 studies.
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The use of oncolytic herpes simplex virus type 1 is a promising stategy for cancer treatment. We constructed herpes simplex virus type 1 vector G47Delta by deleting the alpha47 gene and the promoter region of US11 from G207. We now report studies demonstrating the potential of G47Delta as a therapeutic modality for prostate cancer in combination with androgen ablation. ⋯ These results suggest that oncolytic virus therapy with G47Delta can be usefully combined with androgen ablation therapy for the treatment of prostate cancer.