Effects of Taxotere and taxol on in vitro colony formation of freshly explanted human tumor cells

Ar, Hanauske; Degen, D; Sg, Hilsenbeck; Mc, Bissery; Hoff, Von

doi:10.1097/00001813-199204000-00008

Cited by 117 publications

(28 citation statements)

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“…In vitro, the antiproliferative actions of docetaxel and paclitaxel were studied against a variety of freshly explanted human tumor specimens, including breast, lung, ovarian, and colorectal cancers. At concentrations of 10 mg/ml, 41% of docetaxeltreated specimens achieved significant inhibition, compared with 33% of paclitaxel-treated specimens, demonstrating high cytotoxicity with docetaxel as well as incomplete cross-resistance between the taxanes [5].…”

Section: Molecular Pharmacologymentioning

confidence: 96%

Preclinical Pharmacology of the Taxanes: Implications of the Differences

2004

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Taxanes are one of the most powerful classes of compounds among all chemotherapeutic drugs. Only 30 years separate the isolation of the first taxane from the results of direct clinical comparisons in metastatic breast, ovarian, and lung cancer between the two taxanes available in routine clinical practice. These results suggest a more favorable benefit-to-risk ratio for docetaxel compared to paclitaxel when these drugs are used as single agents or in combination with other chemotherapeutic agents in an every-3-week dosing regimen. Pharmacological data support the difference between the taxanes, likely explaining the clinical results. Considering the molecular pharmacology of the two drugs, docetaxel appears to bind to β β-tubulin with greater affinity and has a wider cell cycle activity than paclitaxel. Docetaxel also appears to have direct antitumoral activity via an apoptotic effect mediated by bcl-2 phosphorylation. In addition, docetaxel has a longer retention time in tumor cells than paclitaxel because of greater uptake and slower efflux. Pharmacokinetics and pharmacodynamics of the taxanes show both agents to be extensively metabolized in the liver, and paclitaxel has a nonlinear pharmacokinetic behavior while docetaxel has linear pharmacokinetics. These differences explain the more simple treatment schedule and favorable results for docetaxel as a single agent and in combination therapy. Last, but not least, there is a pharmacokinetic interaction between paclitaxel and the anthracyclines, an active class of compounds commonly used in the treatment of breast cancer. This pharmacokinetic interaction is associated with greater cardio-and myelotoxicities, which are sequence dependent. These pharmacological data likely explain the different clinical development strategies for the two molecules as well as the different clinical results from individual trials and direct comparisons. The Oncologist 2004;9(suppl 2):3-8 The Oncologist 2004;9(suppl 2):3-8 www.TheOncologist.com

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Section: Molecular Pharmacologymentioning

confidence: 96%

Preclinical Pharmacology of the Taxanes: Implications of the Differences

2004

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“…Docetaxel promotes the polymerization of tubulin and inhibits the disassembly of microtubules, thereby blocking cell division at the M phase during the cell cycle. In vitro colony formation assays have demonstrated the superior anti-tumor activity of docetaxel against many cell lines including ESCC (7,8). A phase II clinical trial of docetaxel monotherapy for the treatment of advanced/recurrent ESCC reported a response rate of 20.4%.…”

Section: Introductionmentioning

confidence: 99%

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Tabuchi

Ozawa

Koyanagi

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Esophageal squamous cell carcinoma (ESCC)is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0x10 -11 to 10 -7 M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC 50 for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0x10 -10 M; TE-2 and TE-3, ≤1.0x10 -9 M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity. This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.

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“…The activity of docetaxel has been demonstrated against a number of freshly explanted and cloned human cancer specimens, including breast cancers (Hanauske et al, 1992;Ringel and Horwitz, 1991).…”

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confidence: 99%

A multicentre phase II study of docetaxel 75 mg m-2 as first-line chemotherapy for patients with advanced breast cancer: report of the Clinical Screening Group of the EORTC

Dièras

Chevallier²,

Kerbrat³

et al. 1996

Br J Cancer

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Summary In this phase II study, 39 women (median age 51 years) with advanced breast cancer received docetaxel (75 mg m-2) intravenously over 1 h every 3 weeks as first-line chemotherapy for advanced disease, without routine premedication for hypersensitivity reactions. In 31 evaluable patients, an overall response rate of 52% (95% CI 33-70%) was achieved, including a complete response rate of 13%. The median time to first response was 12 weeks (range 3-35+), the median duration of response was 34 weeks (range 11 -42+) and the median time to progression was 24 weeks (range 0-42+). Docetaxel showed considerable activity in patients with visceral involvement (52% response), including lung (67%) and liver (44%) metastases. The safety profile was acceptable. Grade 4 neutropenia occurred in 82% of patients (53% of cycles); febrile neutropenia (grade 4 neutropenia with fever >38°C, requiring antibiotics) occurred in only three (7.7%) patients (1.4% of cycles) and none of these required hospitalisation. Acute adverse events were generally well tolerated, with only two grade 3 events and no grade 4 events reported. Despite no prophylactic premedication, the incidence of acute hypersensitivity reactions was only 13%. Fluid retention was widely experienced (72% of patients) but was severe in only five (12.8%) patients and was the reason for discontinuation of treatment in 16 patients.Nevertheless, patients were able to receive a median cumulative dose of approximately 592 mg m-2 before discontinuing treatment, and the syndrome was slowly reversible after treatment withdrawal. In conclusion, docetaxel, even at a dose of 75 mg m-2, is confirmed to be an active agent in breast cancer. Compared with an earlier study of first-line docetaxel at the usual dose of 100 mg -2, it appears that 75 mg m-2 produces a lower response rate (52% vs 68%), although this still compares favourably with that of doxorubicin monotherapy in a similar patient population (43%). This difference is particularly striking in subgroups of patients with particularly poor prognostic factors, such as liver metastases or involvement of more than two organs. The incidence of fluid retention appears to be similar at the two doses and it is likely that premedication with corticosteroids will be preferable to dose reduction for managing this adverse event.

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Effects of Taxotere and taxol on in vitro colony formation of freshly explanted human tumor cells

Cited by 117 publications

References 0 publications

Preclinical Pharmacology of the Taxanes: Implications of the Differences

Preclinical Pharmacology of the Taxanes: Implications of the Differences

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

A multicentre phase II study of docetaxel 75 mg m-2 as first-line chemotherapy for patients with advanced breast cancer: report of the Clinical Screening Group of the EORTC

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