Phase I/II Study of Weekly Docetaxel and Vinblastine in the Treatment of Metastatic Hormone-Refractory Prostate Carcinoma

Tester, William J.; Ackler, Joann; Tijani, Lukman; Leighton, John K.

doi:10.1097/00130404-200607000-00008

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…Although this apparently conflicts with the microtubule stabilizing mechanism of docetaxel therapy, in fact there is a variety of evidence supporting our current findings which suggest that the opposite is true. For example, microtubule depolymerizing drugs vinblastine and vinorelbine have shown potent synergy with docetaxel both in vitro and in early clinical trials 36, 37. Additionally, taxane resistance may be mediated by β‐tubulin mutational modification to induce a more unstable microtubular structure,38 which may not tolerate further destabilization by SAMC treatment.…”

Section: Discussionmentioning

confidence: 99%

Evidence of a novel docetaxel sensitizer, garlic‐derived S‐allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer

Howard

Lee

Chiu

et al. 2008

Intl Journal of Cancer

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The recent introduction of docetaxel in the treatment of hormone refractory prostate cancer (HRPC) has made a small but significant impact on patient survival. However, its effect is limited by intolerance and resistance. The aim of our study was to investigate if the garlic-derived compound, S-allylmercaptocysteine (SAMC), was able to act as a docetaxel sensitizing agent. First, the effect of SAMC on docetaxel sensitivity was examined on 3 HRPC cell lines by colony forming assay. We found that SAMC increased the efficacy of docetaxel on colony forming inhibition by 9-50% compared to single agent treatment. Second, using the HRPC CWR22R nude mice model, we found that the combination of SAMC and docetaxel was 53% more potent than docetaxel alone (p 5 0.037). In addition, there was no additive toxicity in the mice treated with the combination therapy evidenced by histological and functional analysis of liver, kidney and bone marrow. These results suggest that SAMC is able to increase the anticancer effect of docetaxel without causing additional toxic effect in vivo. Third, flow cytometry and Western blotting analysis on HRPC cell lines demonstrated that SAMC promoted docetaxel-induced G2/M phase cell cycle arrest and apoptotic induction. In addition, immunohistochemistry on CWR22R xenograft revealed a suppression of Bcl-2 expression and upregulation of E-cadherin in the SAMC and docetaxel treated animals. These results suggest that SAMC may promote docetaxel-induced cell death through promoting G2/ M cell cycle arrest and apoptosis. Our study implies a potential role for SAMC in improving docetaxel based chemotherapy for the treatment of HRPC.

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Section: Discussionmentioning

confidence: 99%

Evidence of a novel docetaxel sensitizer, garlic‐derived S‐allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer

Howard

Lee

Chiu

et al. 2008

Intl Journal of Cancer

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“…While phase II trials with various combinations of new drugs have suggested promise for emerging docetaxel combination therapies (Oh et al , 2003; Ferrero et al , 2006; Tester et al , 2006; Kikuno et al , 2007; Garcia et al , 2011), of note is the fact that no drug has yet been shown to provide survival benefit when combined with docetaxel in phase III trials (Antonarakis and Eisenberger, 2013). This suggests that there is a need to identify novel compounds for efficacy as single agents or for use in combination with taxane-based therapies.…”

mentioning

confidence: 99%

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

Toner

McLaughlin²,

Giles

et al. 2013

Br J Cancer

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Background:Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer.Methods:The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background.Results:EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102.Conclusion:EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.

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“…Third, the purpose of the measure is to accurately record the pain experienced by the dog regardless of the underlying etiology. Like the BPI, the CBPI maintains internal consistency, stability, and positive validity assessments when applied to bone cancer pain from several potential etiologies [23,[33][34][35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

A Novel Approach to the Use of Animals in Studies of Pain: Validation of the Canine Brief Pain Inventory in Canine Bone Cancer

Brown¹,

Boston²,

Coyne³

et al. 2009

Pain Med

103

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Objective To validate the Canine Brief Pain Inventory (Canine BPI) which is based on the human Brief Pain Inventory (BPI), in a canine model of spontaneous bone cancer. Design and Participants 100 owners of dogs with bone cancer self-administered the Canine BPI on 3 occasions to test the reliability, validity, and responsiveness of the measure. Outcome Measures Factor analysis, internal consistency, convergent validity, and an extreme group validation assessment were completed using the responses from the first administration of the CBPI. Test-retest reliability was evaluated using two administrations of the instrument, one week apart. Responsiveness was tested by comparing responses 3 weeks apart. Results The “severity” and “interference” factors hypothesized based on the BPI were demonstrated in the Canine BPI in dogs with bone cancer. Internal consistency was high (Cronbach’s alpha 0.95 and 0.93), as was test-retest reliability (kappa 0.73 and 0.65). Convergent validity was demonstrated with respect to quality of life (r=0.49 and 0.63). Extreme groups validation against normal dogs showed significantly higher factor scores (P<0.001 for both). Conclusions The Canine BPI reliably measures the same pain constructs in the companion canine model of spontaneous bone cancer as the BPI does in people with bone cancer. This innovative approach to preclinical outcomes development, validating a preclinical outcome measure that directly corresponds to an outcome measure routinely used in clinical research, applied to a readily available animal model of spontaneous disease could transform the predictive ability of preclinical pain studies.

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Phase I/II Study of Weekly Docetaxel and Vinblastine in the Treatment of Metastatic Hormone-Refractory Prostate Carcinoma

Abstract: This combination of weekly docetaxel and vinblastine is effective, well tolerated, and associated with improved quality of life in most of the patients treated. Although estramustine was not given, the risk of thromboembolic disease remains significant.

Cited by 10 publications

References 12 publications

Evidence of a novel docetaxel sensitizer, garlic‐derived S‐allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer

Evidence of a novel docetaxel sensitizer, garlic‐derived S‐allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

A Novel Approach to the Use of Animals in Studies of Pain: Validation of the Canine Brief Pain Inventory in Canine Bone Cancer

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