Anticancer research
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Anticancer research · May 1999
Multicenter Study Clinical Trial Controlled Clinical TrialCombined irinotecan, docetaxel and conventionally fractionated radiotherapy in locally advanced head and neck cancer. A phase I dose escalation study.
Both docetaxel and irinotecan have shown strong radiosensitizing properties in vitro. Encouraging results have been reported by phase I/II studies on combined docetaxel or irinotecan with radiotherapy. In the present study we investigated the feasibility of double radiosensitization with weekly docetaxel and irinotecan in head and neck cancer. ⋯ Of interest, the lowest CR rate was observed in the 3rd dose level (2/4; 50%), which may be a consequence of overall treatment time prolongation. It is concluded that docetaxel and irinotecan combination with radiotherapy is feasible and, a high CR rate can be expected. Combination of the regimen with cytoprotective agents warrant further investigation.
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Anticancer research · Mar 1999
Clinical TrialTreosulfan in the treatment of metastatic renal cell carcinoma.
Treosulfan is a bifunctional alkylating cytostatic agent that has mainly been used in the therapy of advanced ovarian cancer. Lately, a growth inhibiting effect could be detected in human renal cell carcinoma-cell lines as well. In vitro, Treosulfan showed an even higher growth inhibition than Vinblastine. ⋯ Since Treosulfan did not lead to a measurable tumor remission in the given dose regimen, it does not seem to be suitable for the therapy of metastatic renal cell carcinoma.
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Anticancer research · Jan 1999
A novel hydroxamic acid compound, BMD188, demonstrates anti-prostate cancer effects by inducing apoptosis. I: In vitro studies.
Prostate cancer is the most frequently diagnosed malignancy in the Western countries. Apoptosis-targeted drug development could represent a specific and effective weapon against the disease (Tang and Porter, 32: 284-293, 1997). We previously demonstrated that the arachidonate 12-lipoxygenase and its metabolic products could function as survival factors for many solid tumors (Tang et al., Proc. Natl. Acad. Sci. USA 93: 5241-5246, 1996; Tang and Honn, J. Cell. Physiol. 172: 155-170, 1997). ⋯ The data presented here suggest that these novel cyclic hydroxamic acid compounds, via induction of apoptotic death, may find potential clinical applications in the treatment of human prostate cancers.
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Anticancer research · Jan 1999
A novel hydroxamic acid compound, BMD188, demonstrates anti-prostate cancer effects by inducing apoptosis. II: In vivo efficacy and pharmacokinetic studies.
In the preceding paper, we demonstrated that, BMD188 [cis-1-hydroxy-4-(1-naphthyl)-6-octylpiperidine-2-one], a newly synthesized cyclic hydroxamic acid compound, induces potent apoptotic death of prostate cancer cells in vitro. In this project, we studied the in vivo pharmacokinetic behavior and anti-tumor efficacy of this novel compound. ⋯ Collectively, the preceding in vitro and the current in vivo studies suggest that BMD188 and its analogs may find clinical applications in the treatment of prostate cancer patients by inducing apoptotic death of prostate cancer cells.
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Anticancer research · Jan 1999
Antitumor activity of titanocene dichloride in xenografted human renal-cell carcinoma.
Titanocene dichloride [(C5H5)2TiCl2] is a new-developed organometallic antitumor agent which is currently being investigated in clinical trials of phases I and II. In the present study, it was tested for antitumor activity in human renal tumors either growing as monolayers in vitro or as xenografts in athymic mice. For comparison, approved cytostatic drugs (in vitro, vinblastine and 5-fluoro-2'-deoxyuridine; in vivo, cyclophosphamide, vinblastine, and 5-fluorouracil) were administered in vitro and in vivo at equivalent or equitoxic dose levels, respectively. ⋯ Titanocene dichloride was again significantly active in the KTCTL-1M carcinoma xenograft and caused relative growth reductions by 50-65%. In the case of the MRI-H 121 renal sarcoma xenograft, however, the organometallic compound showed an only marginal activity which was surpassed by cyclophosphamide, vinblastine and 5-fluorouracil, all three drugs inducing significant relative growth inhibitions by 50-88%. These results confirm a significant and remarkable antitumor activity of titanocene dichloride in three out of four human renal tumors xenografted to athymic mice and suggest that clinical studies of phase II with titanocene dichloride towards renal-cell carcinoma in human patients should be done in the near future.