High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: Toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome

G. Somlo, J. H. Doroshow, T. Synold, J. Longmate, D. Reardon, W. Chow, S. J. Forman, L. A. Leong, K. A. Margolin, Jr J. Morgan, J. W. Raschko, S. I. Shibata, M. L. Tetef, Y. Yen, N. Kogut, J. Schriber, J. Alvarnas

Research output: Contribution to journalArticle

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Abstract

We assessed the feasibility and pharmacokinetics of high-dose infusional paclitaxel in combination with doxorubicin, cyclophosphamide, and peripheral blood progenitor cell rescue. Between October 1995 and June 1998, 63 patients with high-risk primary [stage II with ≥ 10 axillary nodes involved, stage IIIA or stage IIIB inflammatory carcinoma (n = 53)] or with stage IV responsive breast cancer (n = 10) received paclitaxel 150-775mg/m2 infused over 24 hours, doxorubicin 165mg/m2 as a continuous infusion over 96 hours, and cyclophosphamide 100 mg kg-1. There were no treatment-related deaths. Dose-limiting toxicity was reversible, predominantly sensory neuropathy following administration of paclitaxel at the 775 mg/m2 dose level. Paclitaxel pharmacokinetics were non-linear at higher dose levels; higher paclitaxel dose level, AUC, and peak concentrations were associated with increased incidence of paraesthesias. No correlation between stomatitis, haematopoietic toxicities, and paclitaxel dose or pharmacokinetics was found. Kaplan-Meier estimates of 30-month event-free and overall survival for patients with primary breast carcinoma are 65% (95% CI; 51-83%) and 77% (95% CI; 64-93%). Paclitaxel up to 725 mg/m2 infused over 24 hours in combination with with doxorubicin 165 mg/m2 and cyclophosphamide 100 mg kg-1 is tolerable. A randomized study testing this regimen against high-dose carboplatin, thiotepa and cyclophosphamide (STAMP V) is currently ongoing.

Original languageEnglish
Pages (from-to)1591-1598
Number of pages8
JournalBritish Journal of Cancer
Volume84
Issue number12
DOIs
Publication statusPublished - Jun 15 2001
Externally publishedYes

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Paclitaxel
Doxorubicin
Cyclophosphamide
Blood Cells
Stem Cells
Pharmacokinetics
Breast Neoplasms
Thiotepa
Stomatitis
Paresthesia
Carboplatin
Kaplan-Meier Estimate
Disease-Free Survival
Area Under Curve
Carcinoma
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma : Toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome. / Somlo, G.; Doroshow, J. H.; Synold, T.; Longmate, J.; Reardon, D.; Chow, W.; Forman, S. J.; Leong, L. A.; Margolin, K. A.; Morgan, Jr J.; Raschko, J. W.; Shibata, S. I.; Tetef, M. L.; Yen, Y.; Kogut, N.; Schriber, J.; Alvarnas, J.

In: British Journal of Cancer, Vol. 84, No. 12, 15.06.2001, p. 1591-1598.

Research output: Contribution to journalArticle

Somlo, G, Doroshow, JH, Synold, T, Longmate, J, Reardon, D, Chow, W, Forman, SJ, Leong, LA, Margolin, KA, Morgan, JJ, Raschko, JW, Shibata, SI, Tetef, ML, Yen, Y, Kogut, N, Schriber, J & Alvarnas, J 2001, 'High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: Toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome', British Journal of Cancer, vol. 84, no. 12, pp. 1591-1598. https://doi.org/10.1054/bjoc.2001.1835
Somlo, G. ; Doroshow, J. H. ; Synold, T. ; Longmate, J. ; Reardon, D. ; Chow, W. ; Forman, S. J. ; Leong, L. A. ; Margolin, K. A. ; Morgan, Jr J. ; Raschko, J. W. ; Shibata, S. I. ; Tetef, M. L. ; Yen, Y. ; Kogut, N. ; Schriber, J. ; Alvarnas, J. / High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma : Toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome. In: British Journal of Cancer. 2001 ; Vol. 84, No. 12. pp. 1591-1598.
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abstract = "We assessed the feasibility and pharmacokinetics of high-dose infusional paclitaxel in combination with doxorubicin, cyclophosphamide, and peripheral blood progenitor cell rescue. Between October 1995 and June 1998, 63 patients with high-risk primary [stage II with ≥ 10 axillary nodes involved, stage IIIA or stage IIIB inflammatory carcinoma (n = 53)] or with stage IV responsive breast cancer (n = 10) received paclitaxel 150-775mg/m2 infused over 24 hours, doxorubicin 165mg/m2 as a continuous infusion over 96 hours, and cyclophosphamide 100 mg kg-1. There were no treatment-related deaths. Dose-limiting toxicity was reversible, predominantly sensory neuropathy following administration of paclitaxel at the 775 mg/m2 dose level. Paclitaxel pharmacokinetics were non-linear at higher dose levels; higher paclitaxel dose level, AUC, and peak concentrations were associated with increased incidence of paraesthesias. No correlation between stomatitis, haematopoietic toxicities, and paclitaxel dose or pharmacokinetics was found. Kaplan-Meier estimates of 30-month event-free and overall survival for patients with primary breast carcinoma are 65{\%} (95{\%} CI; 51-83{\%}) and 77{\%} (95{\%} CI; 64-93{\%}). Paclitaxel up to 725 mg/m2 infused over 24 hours in combination with with doxorubicin 165 mg/m2 and cyclophosphamide 100 mg kg-1 is tolerable. A randomized study testing this regimen against high-dose carboplatin, thiotepa and cyclophosphamide (STAMP V) is currently ongoing.",
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T1 - High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma

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AU - Somlo, G.

AU - Doroshow, J. H.

AU - Synold, T.

AU - Longmate, J.

AU - Reardon, D.

AU - Chow, W.

AU - Forman, S. J.

AU - Leong, L. A.

AU - Margolin, K. A.

AU - Morgan, Jr J.

AU - Raschko, J. W.

AU - Shibata, S. I.

AU - Tetef, M. L.

AU - Yen, Y.

AU - Kogut, N.

AU - Schriber, J.

AU - Alvarnas, J.

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N2 - We assessed the feasibility and pharmacokinetics of high-dose infusional paclitaxel in combination with doxorubicin, cyclophosphamide, and peripheral blood progenitor cell rescue. Between October 1995 and June 1998, 63 patients with high-risk primary [stage II with ≥ 10 axillary nodes involved, stage IIIA or stage IIIB inflammatory carcinoma (n = 53)] or with stage IV responsive breast cancer (n = 10) received paclitaxel 150-775mg/m2 infused over 24 hours, doxorubicin 165mg/m2 as a continuous infusion over 96 hours, and cyclophosphamide 100 mg kg-1. There were no treatment-related deaths. Dose-limiting toxicity was reversible, predominantly sensory neuropathy following administration of paclitaxel at the 775 mg/m2 dose level. Paclitaxel pharmacokinetics were non-linear at higher dose levels; higher paclitaxel dose level, AUC, and peak concentrations were associated with increased incidence of paraesthesias. No correlation between stomatitis, haematopoietic toxicities, and paclitaxel dose or pharmacokinetics was found. Kaplan-Meier estimates of 30-month event-free and overall survival for patients with primary breast carcinoma are 65% (95% CI; 51-83%) and 77% (95% CI; 64-93%). Paclitaxel up to 725 mg/m2 infused over 24 hours in combination with with doxorubicin 165 mg/m2 and cyclophosphamide 100 mg kg-1 is tolerable. A randomized study testing this regimen against high-dose carboplatin, thiotepa and cyclophosphamide (STAMP V) is currently ongoing.

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