Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

Carles, Joan; Font, Albert; Mellado, Begoña; Domènech, Montserrat; Gallardo, Enrique; González-Larriba, José-Luis; Catalán, G.; Alfaro, J.; Alba, Arancha González del; Nogué, Miguel; Lianes, P.; Tello, J M

doi:10.1038/sj.bjc.6604030

Cited by 17 publications

(14 citation statements)

References 24 publications

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“…Selective inhibitors of COX-2 have been reported to reduce the formation, growth and metastasis of experimental tumors. Among the COX-2 inhibitors that show promise in cancer therapy is celecoxib, which shows marked efficacy against experimental tumors (6,7) and is currently the subject of ongoing clinical trials (8,9).…”

Section: Introductionmentioning

confidence: 99%

Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells

Ayakawa¹

2009

Mol Med Rep

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Abstract.To ascertain whether meloxicam used in a clinical setting as a non-steroidal anti-inflammatory drug (NSAID) warrants preclinical in vivo evaluation as an anticancer agent, we investigated its antitumor effects alone and in combination with radiation and/or 5-fluorouracil (5-FU) in cultured cells. Seven cell lines were examined for cyclooxygenase-2 (COX-2) protein expression by immunoblot analysis, and the HelaS3, SccVii and eMT6 cell lines were selected, expressing relatively high, intermediate, and relatively low COX-2 levels, respectively. Antitumor effects were examined using a colony assay. Among the three cell lines, the effect of meloxicam alone was strongest in SccVii cells. With 24 h of drug exposure, meloxicam at concentrations of 250 and 1250 µM had a definite antitumor effect, dependent on the drug exposure time. The effect of meloxicam in combination with radiation and/or 5-FU was also investigated in the SccVii cells. at a meloxicam concentration of 250 µM, the antitumor effect in combination with radiation or 5-FU was increased compared to the effect of radiation or 5-FU alone; however, the combined effect appeared to be additive. at lower concentrations, meloxicam had no radiosensitizing effect, nor did it enhance the effect of 5-FU. A meloxicam concentration of 250 µM is considerably higher than concentrations obtained in humans taking meloxicam as an nSaid. in conclusion, the antitumor effect of meloxicam was not correlated with the level of COX-2 protein expression. The effect of meloxicam in combination with radiation and/or 5-FU appeared to be additive. To evaluate the possibility of using meloxicam as an anticancer agent, in vivo investigations at clinically relevant drug dose levels are required.

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Section: Introductionmentioning

confidence: 99%

Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells

Ayakawa¹

2009

Mol Med Rep

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“…Several trials are testing the efficacy of drugs like Docetaxel, Celecoxib and others in combination that can bring down PSA levels, reduce pain and prolong the survival in patients with HRPC. 6 Previous reports in literature have demonstrated that selenium compounds are superior antitumor agents to their corresponding sulfur compounds. 34,35 In particular, seleniumenriched garlic was superior to regular garlic, 36 Se-methylselenocysteine was better than S-methylcysteine, 37 and diallyl selenide was better than diallyl sulfide 38 in mammary cancer prevention.…”

Section: Discussionmentioning

confidence: 99%

“…8 A previous clinical trial using docetaxel in combination with Celecoxib has provided effective treatment for HRPC. 6 Additional reports indicate that the efficacy of chemotherapeutic agents such as doxorubicin, taxol and topoisomerase I inhibitor can be enhanced when used in combination with selenium to control experimental prostate cancer. 12,13 Although the combination regimen is a credible approach, we used an alternative and novel strategy by placing a selenium containing functionality in the backbone of the Celecoxib molecule itself, to generate a new class of compounds named Selenocoxibs.…”

mentioning

confidence: 99%

“…3 NSAIDs have been used in clinical trials for prostate cancer 4,5 and prostate specific antigen (PSA) is the key factor shown to be decreased in these patients, 6 but there may be an associated cardiovascular toxicity that is mainly dose related. 7 Celecoxib (Celebrex), a specific COX-2 inhibitor, reduces prostate tumors in experimental models [8][9][10] mainly through cell cycle regulation and angiogenesis.…”

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confidence: 99%

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Synthesis and antitumor properties of selenocoxib‐1 against rat prostate adenocarcinoma cells

Desai

Sinha

Null

et al. 2010

Intl Journal of Cancer

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Hormone refractory prostate cancer poses a huge problem and standard of care chemotherapy has not been very successful. We used a novel strategy to combine properties of 2 well-studied class of compounds (selenium and COX-2 inhibitor) and examined the resulting effectiveness against prostate cancer. Bearing in mind that sulfonamide moiety and pyrazole ring is important for the proapoptotic activity of Celecoxib, we synthesized a selenium derivative, Selenocoxib-1, by modifying Celecoxib at position 3 of the pyrazole ring. The PAIII cells derived from a metastatic prostate tumor that arose spontaneously in a Lobund-Wistar (LW) rat were used to examine the efficacy of Selenocoxib-1 in vitro. In addition, human metastatic prostate cancer cells, PC-3M, were tested for antitumor effect of Selenocoxib-1 in vitro. The IC 50 in PAIII and PC-3M cells for Selenocoxib-1 was about 5 lM, while for Celecoxib it was more than 20 lM. Selenocoxib-1 induced apoptosis in a dosedependent manner in the PAIII cells. COX-2 expression in PAIII cells was downregulated by Celecoxib and Selenocoxib-1 at 20 and 5 lM, respectively; the COX-2 activity was, however, not affected by Selenocoxib-1. Following treatment with Selenocoxib-1, PAIII cells resulted in dose-dependent decrease in HIF-1a, p-AKT and Bcl-2 levels. A reduction in weights was observed in subcutaneous tumors produced by PAIII cells pretreated with Selenocoxib-1 as compared to Celecoxib in LW rats. Further, following 1 week Selenocoxib-1 treatment of PAIII tumors resulted in significant reduction of tumor weights. This study demonstrates that Selenocoxib-1 is more effective against prostate cancer than Celecoxib.

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“…Recently, there has been evidence of modest biologic activity for celecoxib in men with rising PSA levels after radical prostatectomy and/or radiation therapy for prostate cancer. A recent study suggests that celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel [79].…”

Section: Cox-2 Inhibitors Induce Apoptosis Of Human Prostate Cancer Cmentioning

confidence: 99%

Cyclooxygenase-2 (COX-2): a molecular target in prostate cancer

Gallego¹,

Prado²,

Fonseca

et al. 2007

Clin Transl Oncol

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Epidemiological studies provided the first evidence that COX may be involved in the pathogenesis of cancer. In the process of carcinogenesis and in the route of intracellular signalling during carcinogenesis, COX-2 expression may be a universal phenomenon. In general, COX-2 is up-regulated throughout the tumorigenic process, from early hyperplasia to metastatic disease. COX-2 has been reported to be constitutively overexpressed in a variety of malignancies and is frequently constitutively elevated in prostate carcinoma. COX-2 was consistently overexpressed in premalignant lesions such as prostatic intraepithelial neoplasia, and carcinoma. Cases are described with evolution of proliferative inflammatory atrophy of the prostate and prostate carcinoma. The increase of evidence implicating COX-2 in cancer has stimulated clinical trials to investigate the efficacy of selective COX-2 inhibitors in individuals at risk for human cancer. Regarding prostate carcinoma there is much direct or indirect evidence to support the use of COX-2 inhibitors in this disease. Trials using these drugs in familial adenomatous polyposis (FAP) and other patients with a high risk of colorectal carcinoma are ongoing.

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Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

Cited by 17 publications

References 24 publications

Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells

Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells

Synthesis and antitumor properties of selenocoxib‐1 against rat prostate adenocarcinoma cells

Cyclooxygenase-2 (COX-2): a molecular target in prostate cancer

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