Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Sep 2003
The topoisomerase I inhibitor topotecan increases the sensitivity of prostate tumor cells to TRAIL/Apo-2L-induced apoptosis.
PURPOSE.:TRAIL/Apo-2L is cytotoxic against numerous prostate tumor cell lines; however, some lines are more resistant than others. Identification of an agent that increases prostate tumor cell sensitivity to TRAIL/Apo-2L would prove valuable for TRAIL/Apo-2L-mediated tumor therapy. Thus, we examined the effect of combining five clinically approved chemotherapeutic agents with TRAIL/Apo-2L for treating prostate tumor cells. ⋯ Our results define a promising direction for alternative therapies against androgen-independent prostate cancers. The sensitivity of DU-145 cells to TRAIL/Apo-2L was dramatically increased when combined with topotecan, suggesting that low-dose topotecan treatment to upregulate TRAIL-R1 and TRAIL-R2 and downregulate survivin, followed by TRAIL/Apo-2L administration, may be a viable therapy for treating cancer of the prostate.
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Cancer Chemother. Pharmacol. · Aug 2003
ReviewGranisetron: is there a dose-response effect on nausea and vomiting?
Nausea and vomiting are two of the most debilitating side effects of cytotoxic chemotherapy. Prevention of nausea and vomiting is, thus, very important to ensure that cancer patients continue to receive optimal cytotoxic therapy while seeking to maintain their quality of life. Significant advances in antiemetic therapy have been achieved since the introduction of the 5-HT(3) receptor antagonists, and these agents are currently regarded as first-line antiemetic agents. The aim of this article is to examine the hypothesis that there is a dose-response effect of granisetron for preventing chemotherapy-induced nausea and vomiting in cancer patients. ⋯ Those patients experiencing inadequate control of nausea and vomiting following granisetron may also benefit from retreatment with supplementary doses of granisetron, and over subsequent chemotherapy cycles, these patients should receive granisetron 40 micro g/kg to ensure emesis protection.
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Cancer Chemother. Pharmacol. · Jul 2003
ReviewStrategy for the development of novel anticancer drugs.
Progress in molecular pharmacology has demonstrated each anticancer drug to have a unique molecular target. Recent drug development has focused on compounds that specifically inhibit and/or modify tumor-specific molecular biological changes (target-based drug development). These compounds are generally classified as either small molecules or macromolecules. ⋯ Parameters such as time to progression, changes in tumor markers, and growth rates often vary significantly and are regarded as soft endpoints. Phase III trials evaluating survival benefit require extensive resources, including a large number of patients, a sophisticated data center, and well-trained study groups. The problems and future prospects of novel anticancer drug development are discussed.
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Cancer Chemother. Pharmacol. · Jul 2003
ReviewMonoclonal antibodies for the treatment of hematologic malignancies: clinical trials in Japan.
Of 12 patients with relapsed CD20(+) B-cell non-Hodgkin's lymphoma (B-NHL) enrolled in a phase I study of rituximab, 11 were eligible, and of these 2 achieved a complete response and 5 a partial response. The elimination half-life of rituximab was 445+/-361 h, and serum rituximab levels were detectable at 3 months. In a phase II study, 90 patients with relapsed indolent B-NHL or mantle cell lymphoma (MCL) were treated with infusions of rituximab 375 mg/m(2) once weekly for four doses. ⋯ Gemtuzumab ozogamicin (CMA-676) is a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody. Of 20 patients with relapsed or refractory acute myeloid leukemia enrolled in a "bridging" phase I/II study, 7 showed an objective response. It is concluded that monoclonal antibodies will have play a significant role in the treatment of hematologic malignancies in the future.
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Cancer Chemother. Pharmacol. · Jul 2003
ReviewThe opportunities and challenges of personalized genome-based molecular therapies for cancer: targets, technologies, and molecular chaperones.
There are now unprecedented opportunities for the development of improved drugs for cancer treatment. Following on from the Human Genome Project, the Cancer Genome Project and related activities will define most of the genes in the majority of common human cancers over the next 5 years. This will provide the opportunity to develop a range of drugs targeted to the precise molecular abnormalities that drive various human cancers and opens up the possibility of personalized therapies targeted to the molecular pathology and genomics of individual patients and their malignancies. ⋯ The first-in-class HSP90 inhibitor 17AAG exhibited good activity in animal models and is now showing evidence of molecular and clinical activity in ongoing clinical trials. Novel HSP90 inhibitors are also being sought. The development of HSP90 inhibitors is used to exemplify the application of new technologies in drug discovery against a novel molecular target, and in particular the need for innovative pharmacodynamic endpoints is emphasized as an essential component of hypothesis-testing clinical trials.