A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer

Andrea Rocca, Roberta Maltoni, Alessandro Passardi, Ilaria Massa, Michele Aquilina, Ruggero Ridolfi, Toni Ibrahim, Lorenzo Cecconetto, Samanta Sarti, Elisabetta Pietri, Oriana Nanni, Dino Amadori

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Abstract

Purpose: Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer. Patients and methods: Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1-14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety. Results: Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4-7]). Grade 4 neutropenia occurred in 15% of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin ≥ 560 mg/m2. Conclusions: The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1-14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.

Original languageEnglish
Pages (from-to)871-876
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume65
Issue number5
DOIs
Publication statusPublished - Apr 2010

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Breast Neoplasms
Anthracyclines
Maximum Tolerated Dose
Epirubicin
Febrile Neutropenia
Toxicity
Neutropenia
liposomal doxorubicin
Capecitabine
Monitoring
Safety
Cardiotoxicity

Keywords

  • Breast cancer
  • Capecitabine
  • Cardiac toxicity
  • Liposomal doxorubicin
  • Phase I dose-finding study

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

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title = "A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer",
abstract = "Purpose: Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer. Patients and methods: Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1-14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety. Results: Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4-7]). Grade 4 neutropenia occurred in 15{\%} of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin ≥ 560 mg/m2. Conclusions: The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1-14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.",
keywords = "Breast cancer, Capecitabine, Cardiac toxicity, Liposomal doxorubicin, Phase I dose-finding study",
author = "Andrea Rocca and Roberta Maltoni and Alessandro Passardi and Ilaria Massa and Michele Aquilina and Ruggero Ridolfi and Toni Ibrahim and Lorenzo Cecconetto and Samanta Sarti and Elisabetta Pietri and Oriana Nanni and Dino Amadori",
year = "2010",
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doi = "10.1007/s00280-009-1092-8",
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journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
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TY - JOUR

T1 - A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer

AU - Rocca, Andrea

AU - Maltoni, Roberta

AU - Passardi, Alessandro

AU - Massa, Ilaria

AU - Aquilina, Michele

AU - Ridolfi, Ruggero

AU - Ibrahim, Toni

AU - Cecconetto, Lorenzo

AU - Sarti, Samanta

AU - Pietri, Elisabetta

AU - Nanni, Oriana

AU - Amadori, Dino

PY - 2010/4

Y1 - 2010/4

N2 - Purpose: Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer. Patients and methods: Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1-14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety. Results: Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4-7]). Grade 4 neutropenia occurred in 15% of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin ≥ 560 mg/m2. Conclusions: The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1-14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.

AB - Purpose: Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer. Patients and methods: Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1-14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety. Results: Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4-7]). Grade 4 neutropenia occurred in 15% of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin ≥ 560 mg/m2. Conclusions: The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1-14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.

KW - Breast cancer

KW - Capecitabine

KW - Cardiac toxicity

KW - Liposomal doxorubicin

KW - Phase I dose-finding study

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U2 - 10.1007/s00280-009-1092-8

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JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 5

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