Taxotere™ (docetaxel, D), doxorubicin (Dx) and cyclophosphamide (CTX) (TAC) in the treatment of metastatic breast cancer (MBC)

Among the novel chemotherapeutic drugs introduced in the 1990s, the taxanes have emerged as the most powerful compounds in breast cancer. Both compounds, paclitaxel and docetaxel, have been evaluated in metastatic settings before adjuvant trials proceeded. Docetaxel was shown in several phase III trials to be superior, particularly in terms of survival, for salvaging polychemotherapies after failure of prior chemotherapy, including that with anthracyclines. A benefit of docetaxel was also reported when compared with doxorubicin after failure of alkylating agents. In phase III trials paclitaxel was reported to be as efficacious over 24 hours as doxorubicin 60 mg/m 2 , while paclitaxel was significantly inferior to doxorubicin 75 mg/m 2 over 3 hours and was close to CMF in another trial. The role of taxanes in combination with anthracyclines in first-line therapy of advanced breast cancer is emerging. Following several phase II studies, a phase III trial showed the significant superiority of docetaxel/doxorubicin (AT) versus doxorubicin/cyclophosphamide (AC) in terms of response and time to progression. In several phase II studies with paclitaxel (3 hours), anthracyclines in the metastatic setting showed high efficacy but produced cardiac toxicity related to a pharmacokinetic interaction between the two agents. This finding led to the implementation of metastatic strategies (phase III trials) aimed at avoiding the pharmacokinetic interaction, while the adjuvant strategies with paclitaxel focused primarily on the sequential approach (AC followed by paclitaxel). In contrast, adjuvant strategies with docetaxel/anthracycline-based programs were implemented following both sequential and combination approaches. The Oncologist 2001;6(suppl 3):5-12

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“…Phase I/II studies of docetaxel in combination with doxorubicin involved a number of different regimens [9][10][11][12].…”

Section: Initial Studies Combining Docetaxel With Doxorubicinmentioning

confidence: 99%

Taxane/Anthracycline Combinations: Setting a New Standard in Breast Cancer?

Nabholtz

Riva

2001

The Oncologist

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“…In a clinical study, the combination therapy showed a better cure rate against metastatic breast cancer than the previous therapy. However, the combination of ADR and DOC induces severe myelosuppression (9). DOC is almost always administered as a 1-h infusion at 1 h or immediately after a bolus infusion of ADR.…”

Section: Introductionmentioning

confidence: 99%

Influence of Dosing Schedule on Toxicity and Antitumor Effects of a Combination of Adriamycin and Docetaxel in Mice

Shin

Tabuchi

et al. 2004

Clinical Cancer Research

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Purpose: Although the combination of Adriamycin (ADR) and docetaxel (DOC) showed a better cure rate against metastatic breast cancer in a clinical study, severe myelosuppression and cardiotoxicity were dose-limiting factors. The purpose of this study was to establish the most suitable dosing schedule to relieve severe adverse effects and improve the antitumor effects.Experimental Design: Both ADR and DOC were administered simultaneously in the simultaneous-dosing group (ADR/DOC), whereas in the intermittent-dosing groups (ADR-DOC and DOC-ADR), the second drug was administered 12 h after the first drug. Leukocyte counts and survival were measured to estimate adverse effects. After administration, ADR and DOC concentrations in blood, myelocyte cells, and heart were determined. To clarify the antitumor effect, tumor growth was measured in Ehrlichcell-bearing mice after the initiation of drug injections.Results: The simultaneous-dosing group showed severe leukopenia compared with the saline-treated group. However, the toxicity was reduced in the intermittent-dosing groups. The DOC-ADR group showed the best survival rate in the dosing groups. In the pharmacokinetic study, ADR and DOC concentrations in plasma, myelocyte cells, and the heart were markedly higher in the simultaneous-dosing group than the intermittent-dosing groups. These results indicate that pharmacokinetic interactions may contribute to the change in leukopenia induced by concurrent administration of ADR and DOC. The antitumor effect in the DOC-ADR group was the highest in the dosing groups.Conclusions: In the present study, the findings suggest that ADR administered 12 h after DOC injection (DOC-ADR group) not only inhibits tumor growth more strongly but also significantly reduces leukopenia compared with results for the simultaneous-dosing (ADR/DOC) group and significantly reduced the number of toxic deaths compared with the other groups.

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“…In a clinical study, the combination of docetaxel and adriamycin showed a better cure rate against metastatic breast cancer than other regimens [24]. However, the combination of docetaxel and adriamycin induces severe dose-limiting toxicity [24].…”

Section: Discussionmentioning

confidence: 99%

973 Co-Administration of Piperine and Docetaxel Results in Improved Anti-Tumor Efficacy via Inhibition of Cyp3a4 Activity

et al. 2012

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Background-Docetaxel is the mainline treatment approved by the FDA for castration-resistant prostate cancer (CRPC) yet its administration only increases median survival by two to four months. Docetaxel is metabolized in the liver by hepatic CYP3A4 activity. Piperine, a major plant alkaloid/amide, has been shown to inhibit the CYP3A4 enzymatic activity in a cell-free system. Thus, we investigated whether the co-administration of piperine and docetaxel could increase docetaxel's pharmacokinetic activity in vitro and in vivo.

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Taxotere™ (docetaxel, D), doxorubicin (Dx) and cyclophosphamide (CTX) (TAC) in the treatment of metastatic breast cancer (MBC)

Cited by 10 publications

References 0 publications

Taxane/Anthracycline Combinations: Setting a New Standard in Breast Cancer?

Taxane/Anthracycline Combinations: Setting a New Standard in Breast Cancer?

Influence of Dosing Schedule on Toxicity and Antitumor Effects of a Combination of Adriamycin and Docetaxel in Mice

973 Co-Administration of Piperine and Docetaxel Results in Improved Anti-Tumor Efficacy via Inhibition of Cyp3a4 Activity

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