Activity of Docetaxel With or Without Estramustine Phosphate Versus Mitoxantrone in Androgen Dependent and Independent Human Prostate Cancer Xenografts

Oudard, Stéphane; Legrier, Marie-Emmanuelle; Boyé, Karine; Bras-Gonçalves, Rui; Pinieux, Gonzague de; Crémoux, Patricia de; Poupon, Marie‐France

doi:10.1097/01.ju.0000062500.75703.2c

Cited by 47 publications

(28 citation statements)

References 15 publications

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“…In contrast, apoptosis could not be demonstrated in a docetaxel-treated human prostate cancer xenograft (Oudard et al, 2003). We here report that both docetaxel and vinorelbine induce significant increases in serum CK18-Asp396 in HRPC patients.…”

Section: Discussionmentioning

confidence: 66%

Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles

et al. 2006

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Caspase-cleaved proteins are released from disintegrated apoptotic cells and can be detected in the circulation. We here addressed whether caspase-cleaved cytokeratin 18 (CK18-Asp396) can be used as a serum biomarker for assessment of the clinical efficiency of chemotherapy in hormone-refractory prostate cancer (HRPC). A total of 82 patients with HRPC were evaluated during 751 treatment cycles, either with estramustine (EMP)/vinorelbine or with EMP/docetaxel. The levels of CK18-Asp396 and of total CK18 were measured in patient serum before and during therapy by ELISA. Docetaxel induced significant increases in serum CK18-Asp396 (Po0.0001) and total CK18 (Po0.0002), suggesting induction of apoptosis. Similarly, vinorelbine induced increases in both CK18-Asp396 and CK18 (Po0.001 and 0.011). In contrast, EMP induced increases in total serum CK18 (Po0.0001), but not in CK18-Asp396 (P ¼ 0.13). The amplitudes of docetaxel-induced increases were associated with baseline prostate-specific antigen (PSA) and CK18 serum levels in these patients, consistent with tumoral origin of caspase-cleaved fragments. Docetaxel induced significant increases in CK18-Asp396 during second-, third-and fourth-line therapy and induced increased levels of CK18-Asp396 during treatment cycles 1 -8. In contrast, vinorelbine induced significant increases only during cycles 1 -3. In a subgroup of 32 patients that received EMP/vinorelbine in second line followed by EMP/docetaxel in third line, docetaxel induced stronger increases than vinorelbine (P ¼ 0.008). These results show that the CK18-Asp396 serum marker can be used to assess tumour apoptosis in vivo and suggest that the clinical efficiency of docetaxel in HRPC is due to induction of apoptosis during multiple treatment cycles.

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Section: Discussionmentioning

confidence: 66%

Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles

et al. 2006

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“…Hormone-refractory prostate cancer (HRPC) was regarded as chemoresistant, until the recent demonstration of taxane activity (Petrylak et al, 1999). A preclinical in vivo study using our PAC120 model of hormone-dependent (HD) human prostate cancer xenograft confirmed these data (de Pinieux et al, 2001;Oudard et al, 2003). A randomised phase II study demonstrated the efficacy of docetaxel-based chemotherapy vs a mitoxantroneprednisone combination, significantly decrease PSA and prolongs time to progression of metastatic HRPC patients (Oudard et al, 2005).…”

mentioning

confidence: 58%

Potentiation of antitumour activity of docetaxel by combination with trastuzumab in a human prostate cancer xenograft model and underlying mechanisms

et al. 2007

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Antitumour activity of docetaxel (Taxotere s ) in hormone-dependent (HD) and hormone-independent (HID) prostate cancer PAC120 xenograft model was previously reported, and its level was associated with HER2 protein expression. In the present study, we evaluate the antitumour effects of docetaxel combined with trastuzumab (Herceptin s ), an anti-HER2 antibody. Although trastuzumab alone had no effect on tumour growth, it potentiated the antitumour activity of docetaxel in HD tumours and more strongly in HID variants. Using the HID28 variant, we show that docetaxel treatment of tumour-bearing mice induces an increased HER2 mRNA expression of the tyrosine kinase receptor of 25-fold 24 h after docetaxel treatment, while HER2 protein and p-AKT decreased. This was followed by an increase of HER2 protein 3 days (two-fold) after docetaxel treatment and by a strong HER2 release in the serum of treated mice; expression of phospho-ERK, p27, BCL2 and HSP70 concomitantly increased. Similar molecular alterations were induced by docetaxel plus trastuzumab combination, except for that there was a transient and complete disappearance of AR and HSP90 proteins 24 h after treatment. We show that in addition to its known effects on tubulin and mitotic spindles, docetaxel induces complex signalisation pathway mechanisms in surviving cells, including HER2, which can be pharmacologically targeted. This study suggests that the docetaxel/trastuzumab combination may prove an effective therapeutic approach for HER2-expressing hormone-refractory prostate cancer. Escape from androgen ablation therapy is a constant feature of prostate cancer progression, leaving patients with few therapeutic options. Hormone-refractory prostate cancer (HRPC) was regarded as chemoresistant, until the recent demonstration of taxane activity (Petrylak et al, 1999). A preclinical in vivo study using our PAC120 model of hormone-dependent (HD) human prostate cancer xenograft confirmed these data (de Pinieux et al, 2001;Oudard et al, 2003). A randomised phase II study demonstrated the efficacy of docetaxel-based chemotherapy vs a mitoxantroneprednisone combination, significantly decrease PSA and prolongs time to progression of metastatic HRPC patients (Oudard et al, 2005). Despite these encouraging preclinical and clinical data, the therapeutic efficacy of taxane-based chemotherapy of HRPC remains modest. A better knowledge of the mechanisms of tumour hormonal escape and of key molecular targets is needed to design more effective combination therapies for HRPC.Several preclinical studies have implicated the ERBB family of tyrosine kinase receptors, especially HER2, in the progression of prostate cancer to a hormone-refractory state. The CWR22 hormone-independent prostate cancer xenograft expresses HER2 and its growth is inhibited in vivo by an anti-HER2 antibody (Agus et al, 1999;Mendoza et al, 2002). Increased hormone independence in prostate cancer cells was associated with androgen receptor (AR) phosphorylation mediated by transfected HER2 (Craft et al, 1999;Yeh e...

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“…12 Docetaxel blocks the cell cycle in the G 2 /M phase. 15,23 Lokeshwar et al 16 demonstrated that 80% of all tumor cells are blocked in the G 2 /M phase 24 h after the administration of i.p. paclitaxel in Dunning tumors implanted in Copenhagen rats.…”

Section: Discussionmentioning

confidence: 99%

“…The choice of the doses and the protocol of docetaxel administration were made according to an optimal balance of efficacy and tolerance, as previously tested in the litterature. 15 …”

Section: Treatment Sessionmentioning

confidence: 99%

Influence of the docetaxel administration period (neoadjuvant or concomitant) in relation to HIFU treatment on the growth of Dunning tumors: results of a preliminary study

Paparel

Chapelon

Bissery

et al. 2007

Prostate Cancer Prostatic Dis

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The objective of this study was to evaluate mechanisms of the synergy between high intensityfocused ultrasound (HIFU) and docetaxel and to determine the best sequence of chemotherapy administration in relation to HIFU treatment for obtaining optimum control of tumoral growth. A total of 15 days after s.c. implantation of the tumor, 52 Copenhagen rats studied were randomized in 4 groups of 13: controls, docetaxel alone (group 1), HIFU and docetaxel concomitant (group 2) and HIFU and docetaxel administered 24 h before treatment (group 3). The number of HIFU shots was calculated in order to cover 75% of the tumor volume. The effects of docetaxel, HIFU and their interaction on tumor volumes were analyzed using a linear regression. The distributions of the tumor volumes were significantly greater in the control group than in the group 1 (P ¼ 0.002) and than in both groups 2 and 3 (Po0.0001 and P ¼ 0.0001). These volumes were also significantly greater in group 1 than in both groups 2 and 3 and there was no difference between the groups 2 and 3. The tumor doubling times were 7.8 days for the group 1, 43.8 days for the group 2, 16.1 days for the group 3 and 5.9 days for the controls. The mechanism of the synergy between HIFU and docetaxel on the growth of Dunning tumors is apparently multifaceted. The results are encouraging because in the two groups of rats treated with the combination of HIFU and docetaxel, the percentage of complete remission was approximately 30%.

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Activity of Docetaxel With or Without Estramustine Phosphate Versus Mitoxantrone in Androgen Dependent and Independent Human Prostate Cancer Xenografts

Cited by 47 publications

References 15 publications

Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles

Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles

Potentiation of antitumour activity of docetaxel by combination with trastuzumab in a human prostate cancer xenograft model and underlying mechanisms

Influence of the docetaxel administration period (neoadjuvant or concomitant) in relation to HIFU treatment on the growth of Dunning tumors: results of a preliminary study

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