Paclitaxel Versus Doxorubicin as First-Line Single-Agent Chemotherapy for Metastatic Breast Cancer: A European Organization for Research and Treatment of Cancer Randomized Study With Cross-Over

Paridaens, Robert; Biganzoli, Laura; Bruning, P.F.; Klijn, Jan G.M.; Gamucci, Teresa; Houston, Stephen; Coleman, Robert E.; Schachter, Jacob; Vreckem, A. Van; Sylvester, Richard; Awada, Ahmad; Wildiers, J.; Piccart, Martine

doi:10.1200/jco.2000.18.4.724

Cited by 327 publications

(156 citation statements)

References 31 publications

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“…By contrast, there is no standard regimen recommended in the metastatic setting. In cases with life-threatening metastatic lesions or rapidly growing tumors, regimens that are expected to control lesions quickly, such as simultaneous administration of taxanes and anthracyclines, or taxanes in combination with either gemcitabine, capecitabine or bevacizumab, should be applied (4)(5)(6)(7)(8)(9)(20)(21)(22)(23). However, a proportion of the patients exhibit disease progression during or after receiving these cytotoxic regimens, even if favorable combinations are selected.…”

Section: Discussionmentioning

confidence: 99%

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Kontani

Hashimoto

Murazawa

et al. 2016

Molecular and Clinical Oncology

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Abstract.The survival of patients with metastatic breast cancer (MBC) has not improved, despite recent advances in therapeutic strategies. This is mainly due to the fact that cytotoxic agents cannot be administered over a long period, even if they exhibit favorable activity, due to treatment-related side effects or acquisition of tumor resistance to the administered agents. Thus, the development of therapeutic strategies that may be used over a long time period is required to improve survival. We assessed the availability and clinical outcomes of metronomic chemotherapy, which is defined as continuous or frequent treatment with low doses of cytotoxic drugs. A total of 80 patients with MBC received chemotherapy in the metastatic setting, and the clinicopathological factors and clinical outcomes were retrospectively compared between 52 patients who received metronomic regimens and 28 patients who received other cytotoxic regimens. As regards clinical outcomes, the median time-to-treatment failure (TTF) and overall survival (OS) were significantly longer in the metronomic group compared with those in the non-metronomic group (TTF, 15 vs. 4 months, P=0.0001; and OS, 53 vs. 28 months P=0.0012, respectively). In the metronomic group, none of the 18 patients who responded to the regimen had triple-negative (TN) cancer (17 had luminal-type tumors and 1 had a human epidermal factor receptor 2-type tumor). Furthermore, TTF and OS were significantly longer in patients with non-TN cancer compared with those in patients with TN cancer in the metronomic group (TTF, 16 vs. 7 months, P=0.0014; and OS, 108 vs. 20 months, P=0.000007, respectively). The proportion of patients who experienced treatment-related adverse events was significantly lower in the metronomic group compared with that in the non-metronomic group (36.5 vs. 61.5%, respectively; P=0.038). In conclusion, metronomic chemotherapy is a viable option for luminal-type MBC in terms of effectiveness and minimal toxicity, regardless of metastatic sites or prior treatment. However, an alternative treatment is required for TN cancer.

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Section: Discussionmentioning

confidence: 99%

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Kontani

Hashimoto

Murazawa

et al. 2016

Molecular and Clinical Oncology

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“…[1][2][3][4][5][6][7] The effectiveness of paclitaxel in metastatic anthracycline-resistant breast cancer led to several large adjuvant clinical trials. The first of these to be reported, US Intergroup trial INT 0148 (CALGB 9344), demonstrated an improvement in diseasefree and overall survival from the addition of four cycles of paclitaxel to four cycles of cyclophosphamide and doxorubicin.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

Dougherty¹,

Schumaker²,

Jordan³

et al. 2004

Cancer Biology & Therapy

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ACKNOWLEDGEMENTS Research Paper Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer ABSTRACTA retrospective analysis of CALGB trial 9344 suggested paclitaxel administration following cyclophosphamide and doxorubicin adjuvant chemotherapy is most beneficial for patients with ERα negative (ERα-) breast cancer. Since the cytotoxic effects of paclitaxel are cell cycle dependent, we postulated that the relationship between ERα and the effectiveness of adjuvant paclitaxel reflects the observation that ERα positive (ERα+) breast cancers proliferate more slowly than ERα-breast cancers. Three in vitro models (MCF-7, T47D and ZR-75) were examined to compare growth rates and paclitaxelinduced apoptosis in ERα+ and ERα-clones of the same, originally ERα+ cell line. For the T47D and ZR-75 cell lines, loss of ERα was associated with a decrease in doubling time and an increase in paclitaxel sensitivity. However, when cell culture conditions were altered to achieve equivalent cell proliferation rates, no difference in paclitaxel sensitivity was observed. Similarly, an ERα-clone of MCF-7 cells that did not exhibit an enhanced growth rate compared to its ERα+ counterpart also did not show increased paclitaxel sensitivity. The combined apoptotic effects of tamoxifen and paclitaxel on MCF-7 cells were not synergistic or even clearly additive. In these in vitro models, the effectiveness of paclitaxel correlated more closely with growth rate than ERα expression. These data suggest that measurements of tumor proliferation may provide more accurate predictive markers for the benefits of adjuvant paclitaxel than ERα analysis.

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“…We identified 21 eligible studies, of which three are ongoing (Table 2) (Dieras et al, 1995;Bishop et al, 1999;Chan et al, 1999;Nabholtz et al, 1999Nabholtz et al, , 2003Sjostrom et al, 1999;Luck et al, 2000;Paridaens et al, 2000;Bonneterre et al, 2001Bonneterre et al, , 2002Bonneterre et al, , 2003Jassem et al, 2001;Zielinski et al, 2001;Biganzoli et al, 2002;Icli et al, 2002;Talbot et al, 2002;Bontenbal et al, 2003;Sledge et al, 2003;Goldhirsch, 2005;Heidemann, 2005). An additional two studies were identified but excluded: the status of one as a randomised trial was unclear (Gebbia et al, 2003), and the second randomised women to cease vs continue paclitaxel (Gennari et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

A systematic review of taxane-containing regimens for metastatic breast cancer

2005

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We compared the results of randomised trials comparing taxane-containing chemotherapy regimens with regimens not containing a taxane in women with metastatic breast cancer. The specialised register of the Cochrane Breast Cancer Group was searched in March 2004. Eligibility was assessed and data extracted from eligible studies by two reviewers. Hazard ratios (HR) were derived for time-to-event outcomes, and a fixed-effect model was used for meta-analysis. Tumour response rates were analysed as dichotomous variables. Of 21 eligible trials, 16 had published some results and 12 data on overall survival. An estimated 2621 deaths among 3643 women suggest a significant difference in overall survival in favour of taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.86 -1.00, P ¼ 0.05). The treatment effect on survival was similar if only trials of first-line chemotherapy were included, although not statistically significant. There appeared to be an advantage for taxanes in time to progression (HR 0.92, 95% CI 0.85 -0.99, P ¼ 0.02) and overall response (odds ratio (OR) 1.34, 95% CI 1.18 -1.52, Po0.001). There was significant heterogeneity across the trials (Po0.001), partly because of the varying efficacy of the comparator regimens. Taxane-containing regimens improved overall survival in women with metastatic breast cancer. Taxane-containing regimens are more effective than some, but not all, nontaxanecontaining regimens. British Journal of Cancer (2005) Taxanes are among the most active chemotherapy agents used in the management of metastatic breast cancer. Paclitaxel was identified in 1971 as part of a National Cancer Institute (NCI) programme that screened medicinal plants for potential anticancer activity, and was first used in clinical trials in 1983 (Breast cancer: taxane clinical perspectives, 1996). Docetaxel was synthesised in 1986 and is similar to paclitaxel in its mechanism of action.Initially, the use of taxanes was limited by hypersensitivity reactions, but once these were better managed (largely by premedication with steroids), taxane use became more frequent. Taxanes have become part of standard management in most western countries and are used as single agents or in combination with other chemotherapeutic drugs or the monoclonal antibody trastuzumab (Bernard-Marty et al, 2003).The effect of taxanes on survival compared with other drugs or drug combinations is unclear. We therefore conducted a systematic review and meta-analysis to identify and synthesise the results of randomised clinical trials comparing taxanecontaining chemotherapy regimens with regimens that did not contain a taxane. Prospectively, we asked the following questions:(Q1) Regimen A plus taxane vs Regimen A (e.g. doxorubicin plus docetaxel vs doxorubicin alone) (Q2) Regimen A plus taxane vs Regimen B (e.g. doxorubicin plus docetaxel vs doxorubicin plus cyclophosphamide) (Q3) Single agent taxane vs Regimen C (e.g. docetaxel vs doxorubicin plus cyclophosphamide).The planned outcome measures were survival (date randomised to...

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Paclitaxel Versus Doxorubicin as First-Line Single-Agent Chemotherapy for Metastatic Breast Cancer: A European Organization for Research and Treatment of Cancer Randomized Study With Cross-Over

Cited by 327 publications

References 31 publications

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

A systematic review of taxane-containing regimens for metastatic breast cancer

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