Compilation of phase I and II trial data of docetaxel and doxorubicin in the treatment of advanced breast cancer and other malignancies

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Abstract

Doxorubicin and docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France) are the most active cytotoxic agents in the treatment of advanced breast cancer. In the pre-taxane era, randomized trials demonstrated that doxorubicin-containing chemotherapy regimens are associated with higher response rates and improved survival compared with non-doxorubicin-containing regimens. Doxorubicin-containing regimens were therefore considered the standard of care at that time. Because of the substantial activity of the taxanes in anthracycline-resistant breast cancer, there is a clear rationale for combining doxorubicin with the taxanes as initial therapy for patients with metastatic disease. The combination of doxorubicin plus paclitaxel has been extensively studied. Impressive response rates were noted in at least two studies, although the treatment also resulted in an unacceptably high risk of congestive heart failure. Paclitaxel is known to perturb the metabolism of doxorubicin, thereby increasing drug exposure and augmenting the cardiotoxicity of the anthracycline. The cardiotoxicity of the combination may be ameliorated by restricting the cumulative doxorubicin dose to less than 360 mg/m2, by increasing the interval between administration of the two drugs to at least 4 hours, or by adding the cardioprotective agent dexrazoxane. The Eastern Cooperative Oncology Group performed a randomized phase III trial comparing doxorubicin alone, paclitaxel alone, or the doxorubicin/paclitaxel combination in patients with metastatic breast cancer. Although the response rate and time to treatment failure improved with the combination, survival did not. There has been two phase II trials investigating the combination of doxorubicin plus docetaxel. The regimen was highly effective and did not seem to be associated with an increased risk of congestive heart failure. The findings justify further evaluation of the doxorubicin/docetaxel combination in patients with advanced and operable breast cancer. Such trials are currently in progress and will define the role for this combination in the management of patients with breast cancer.

Original languageEnglish (US)
Pages (from-to)10-15
Number of pages6
JournalSeminars in Oncology
Volume25
Issue number6 SUPPL. 13
StatePublished - 1998

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docetaxel
Doxorubicin
Breast Neoplasms
Neoplasms
Paclitaxel
Therapeutics
Taxoids
Anthracyclines
Heart Failure
Dexrazoxane
Cardiotonic Agents

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Compilation of phase I and II trial data of docetaxel and doxorubicin in the treatment of advanced breast cancer and other malignancies",
abstract = "Doxorubicin and docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France) are the most active cytotoxic agents in the treatment of advanced breast cancer. In the pre-taxane era, randomized trials demonstrated that doxorubicin-containing chemotherapy regimens are associated with higher response rates and improved survival compared with non-doxorubicin-containing regimens. Doxorubicin-containing regimens were therefore considered the standard of care at that time. Because of the substantial activity of the taxanes in anthracycline-resistant breast cancer, there is a clear rationale for combining doxorubicin with the taxanes as initial therapy for patients with metastatic disease. The combination of doxorubicin plus paclitaxel has been extensively studied. Impressive response rates were noted in at least two studies, although the treatment also resulted in an unacceptably high risk of congestive heart failure. Paclitaxel is known to perturb the metabolism of doxorubicin, thereby increasing drug exposure and augmenting the cardiotoxicity of the anthracycline. The cardiotoxicity of the combination may be ameliorated by restricting the cumulative doxorubicin dose to less than 360 mg/m2, by increasing the interval between administration of the two drugs to at least 4 hours, or by adding the cardioprotective agent dexrazoxane. The Eastern Cooperative Oncology Group performed a randomized phase III trial comparing doxorubicin alone, paclitaxel alone, or the doxorubicin/paclitaxel combination in patients with metastatic breast cancer. Although the response rate and time to treatment failure improved with the combination, survival did not. There has been two phase II trials investigating the combination of doxorubicin plus docetaxel. The regimen was highly effective and did not seem to be associated with an increased risk of congestive heart failure. The findings justify further evaluation of the doxorubicin/docetaxel combination in patients with advanced and operable breast cancer. Such trials are currently in progress and will define the role for this combination in the management of patients with breast cancer.",
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AU - Sparano, Joseph A.

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AB - Doxorubicin and docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France) are the most active cytotoxic agents in the treatment of advanced breast cancer. In the pre-taxane era, randomized trials demonstrated that doxorubicin-containing chemotherapy regimens are associated with higher response rates and improved survival compared with non-doxorubicin-containing regimens. Doxorubicin-containing regimens were therefore considered the standard of care at that time. Because of the substantial activity of the taxanes in anthracycline-resistant breast cancer, there is a clear rationale for combining doxorubicin with the taxanes as initial therapy for patients with metastatic disease. The combination of doxorubicin plus paclitaxel has been extensively studied. Impressive response rates were noted in at least two studies, although the treatment also resulted in an unacceptably high risk of congestive heart failure. Paclitaxel is known to perturb the metabolism of doxorubicin, thereby increasing drug exposure and augmenting the cardiotoxicity of the anthracycline. The cardiotoxicity of the combination may be ameliorated by restricting the cumulative doxorubicin dose to less than 360 mg/m2, by increasing the interval between administration of the two drugs to at least 4 hours, or by adding the cardioprotective agent dexrazoxane. The Eastern Cooperative Oncology Group performed a randomized phase III trial comparing doxorubicin alone, paclitaxel alone, or the doxorubicin/paclitaxel combination in patients with metastatic breast cancer. Although the response rate and time to treatment failure improved with the combination, survival did not. There has been two phase II trials investigating the combination of doxorubicin plus docetaxel. The regimen was highly effective and did not seem to be associated with an increased risk of congestive heart failure. The findings justify further evaluation of the doxorubicin/docetaxel combination in patients with advanced and operable breast cancer. Such trials are currently in progress and will define the role for this combination in the management of patients with breast cancer.

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