High-dose consolidation chemotherapy with idarubicin and alkylating agents following induction with gemcitabine-epirubicin-paclitaxel in metastatic breast cancer: A dose finding study

C. Bengala, R. Danesi, V. Guarneri, I. Pazzagli, S. Donati, C. Favre, S. Fogli, O. Biadi, F. Innocenti, M. Del Tacca, M. Mariani, P. F. Conte

Research output: Contribution to journalArticle

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Abstract

Preliminary randomized studies have failed to show a survival benefit of high-dose chemotherapy with alkylators in advanced breast cancer. Idarubicin is an active agent in breast cancer and is suitable for dose escalation. We designed a dose finding study with escalating high-dose idarubicin (HD-Ida) followed by fixed high-dose thiotepa + melphalan (HD-TM) with peripheral blood progenitor cells (PBPC) in MBC patients with stable disease or in partial response after six courses of induction chemotherapy with gemcitabine 1000 mg/m2 days 1 and 4, epirubicin 90 mg/m2 day 1, taxol 175 mg/m2 day 1 (GET). Aims of the study were to identify the maximum tolerated dose (MTD) of idarubicin, to evaluate the cardiac safety and activity of HD-Ida and HD-TM after GET and to study the pharmacokinetic profile of idarubicin and idarubicinol. A total of 14 patients were treated. Idarubicin was administered as a 48 h continuous i.v. infusion at the following dose levels: 40 mg/m2 (three patients), 50 mg/m2 (three patients), 60 mg/m2 (five patients) and 70 mg/m2 (three patients). Mucositis was the dose-limiting toxicity and the MTD was 60 mg/m2. Cmax of Idarubicin and idarubicinol were 7.7 ± 2.0 and 26.3 ± 9.7 ng/ml at 40 mg/m2 and increased to 14.8 + 3.0 and 47.4 + 12.6 ng/ml at 70 mg/m2. AUCto-264 of idarubicin and idarubicinol increased from 423.2 ± 111.6 and 2581 ± 606 hng/ml at 40 mg/m2 to 732.8 ± 140.2 and 4590 ± 1258 hng/ml at 70 mg/m2. Conversion rates after HD-Ida and HD-TM were 28.6 and 38.5%, respectively. No episodes of cardiac toxicity were observed. We conclude that HD-Ida followed by HD-TM is feasible and devoid of cardiac toxicity. Moreover, the activity of HD-Ida after a epirubicin-containing regimen suggests incomplete cross-resistance between the two drugs.

Original languageEnglish
Pages (from-to)275-280
Number of pages6
JournalBone Marrow Transplantation
Volume31
Issue number4
DOIs
Publication statusPublished - Feb 2003

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gemcitabine
Consolidation Chemotherapy
Idarubicin
Epirubicin
Alkylating Agents
Paclitaxel
Breast Neoplasms
Thiotepa
Melphalan
Maximum Tolerated Dose
Mucositis
Induction Chemotherapy

Keywords

  • High-dose chemotherapy
  • Idarubicin
  • Metastatic breast cancer

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

High-dose consolidation chemotherapy with idarubicin and alkylating agents following induction with gemcitabine-epirubicin-paclitaxel in metastatic breast cancer : A dose finding study. / Bengala, C.; Danesi, R.; Guarneri, V.; Pazzagli, I.; Donati, S.; Favre, C.; Fogli, S.; Biadi, O.; Innocenti, F.; Del Tacca, M.; Mariani, M.; Conte, P. F.

In: Bone Marrow Transplantation, Vol. 31, No. 4, 02.2003, p. 275-280.

Research output: Contribution to journalArticle

Bengala, C. ; Danesi, R. ; Guarneri, V. ; Pazzagli, I. ; Donati, S. ; Favre, C. ; Fogli, S. ; Biadi, O. ; Innocenti, F. ; Del Tacca, M. ; Mariani, M. ; Conte, P. F. / High-dose consolidation chemotherapy with idarubicin and alkylating agents following induction with gemcitabine-epirubicin-paclitaxel in metastatic breast cancer : A dose finding study. In: Bone Marrow Transplantation. 2003 ; Vol. 31, No. 4. pp. 275-280.
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abstract = "Preliminary randomized studies have failed to show a survival benefit of high-dose chemotherapy with alkylators in advanced breast cancer. Idarubicin is an active agent in breast cancer and is suitable for dose escalation. We designed a dose finding study with escalating high-dose idarubicin (HD-Ida) followed by fixed high-dose thiotepa + melphalan (HD-TM) with peripheral blood progenitor cells (PBPC) in MBC patients with stable disease or in partial response after six courses of induction chemotherapy with gemcitabine 1000 mg/m2 days 1 and 4, epirubicin 90 mg/m2 day 1, taxol 175 mg/m2 day 1 (GET). Aims of the study were to identify the maximum tolerated dose (MTD) of idarubicin, to evaluate the cardiac safety and activity of HD-Ida and HD-TM after GET and to study the pharmacokinetic profile of idarubicin and idarubicinol. A total of 14 patients were treated. Idarubicin was administered as a 48 h continuous i.v. infusion at the following dose levels: 40 mg/m2 (three patients), 50 mg/m2 (three patients), 60 mg/m2 (five patients) and 70 mg/m2 (three patients). Mucositis was the dose-limiting toxicity and the MTD was 60 mg/m2. Cmax of Idarubicin and idarubicinol were 7.7 ± 2.0 and 26.3 ± 9.7 ng/ml at 40 mg/m2 and increased to 14.8 + 3.0 and 47.4 + 12.6 ng/ml at 70 mg/m2. AUCto-264 of idarubicin and idarubicinol increased from 423.2 ± 111.6 and 2581 ± 606 hng/ml at 40 mg/m2 to 732.8 ± 140.2 and 4590 ± 1258 hng/ml at 70 mg/m2. Conversion rates after HD-Ida and HD-TM were 28.6 and 38.5{\%}, respectively. No episodes of cardiac toxicity were observed. We conclude that HD-Ida followed by HD-TM is feasible and devoid of cardiac toxicity. Moreover, the activity of HD-Ida after a epirubicin-containing regimen suggests incomplete cross-resistance between the two drugs.",
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AU - Pazzagli, I.

AU - Donati, S.

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AU - Fogli, S.

AU - Biadi, O.

AU - Innocenti, F.

AU - Del Tacca, M.

AU - Mariani, M.

AU - Conte, P. F.

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N2 - Preliminary randomized studies have failed to show a survival benefit of high-dose chemotherapy with alkylators in advanced breast cancer. Idarubicin is an active agent in breast cancer and is suitable for dose escalation. We designed a dose finding study with escalating high-dose idarubicin (HD-Ida) followed by fixed high-dose thiotepa + melphalan (HD-TM) with peripheral blood progenitor cells (PBPC) in MBC patients with stable disease or in partial response after six courses of induction chemotherapy with gemcitabine 1000 mg/m2 days 1 and 4, epirubicin 90 mg/m2 day 1, taxol 175 mg/m2 day 1 (GET). Aims of the study were to identify the maximum tolerated dose (MTD) of idarubicin, to evaluate the cardiac safety and activity of HD-Ida and HD-TM after GET and to study the pharmacokinetic profile of idarubicin and idarubicinol. A total of 14 patients were treated. Idarubicin was administered as a 48 h continuous i.v. infusion at the following dose levels: 40 mg/m2 (three patients), 50 mg/m2 (three patients), 60 mg/m2 (five patients) and 70 mg/m2 (three patients). Mucositis was the dose-limiting toxicity and the MTD was 60 mg/m2. Cmax of Idarubicin and idarubicinol were 7.7 ± 2.0 and 26.3 ± 9.7 ng/ml at 40 mg/m2 and increased to 14.8 + 3.0 and 47.4 + 12.6 ng/ml at 70 mg/m2. AUCto-264 of idarubicin and idarubicinol increased from 423.2 ± 111.6 and 2581 ± 606 hng/ml at 40 mg/m2 to 732.8 ± 140.2 and 4590 ± 1258 hng/ml at 70 mg/m2. Conversion rates after HD-Ida and HD-TM were 28.6 and 38.5%, respectively. No episodes of cardiac toxicity were observed. We conclude that HD-Ida followed by HD-TM is feasible and devoid of cardiac toxicity. Moreover, the activity of HD-Ida after a epirubicin-containing regimen suggests incomplete cross-resistance between the two drugs.

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