Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer

Amita Patnaik, Janet MacKinnon, Paul Goss, Tracy Nagy, Alexander Keith Stewart, Armand Keating, Michael Crump

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high Complete and overall response rates in metastatic breast cancer (MBC). Patients and Methods: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline- based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m2/d and mitoxantrone 16 mg/m2/d combined with escalating doses of carboplatin 200 to 500 mg/m2/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 μg/d subcutaneously starting on day 1. Results: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with ≤ 400 mg/m2 of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 109/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 109/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). Conclusion: The maximum-tolerated dose of carboplatin was 400 mg/m2/d in combination with mitoxantrone 16 mg/m2/d and cyclophosphamide 1,500 mg/m2, all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish (US)
Pages (from-to)2363-2368
Number of pages6
JournalJournal of Clinical Oncology
Volume18
Issue number12
StatePublished - Jun 2000
Externally publishedYes

Fingerprint

Mitoxantrone
Carboplatin
Cyclophosphamide
Breast Neoplasms
Peripheral Blood Stem Cell Transplantation
Drug Therapy
Maximum Tolerated Dose
Poisons
Anthracyclines
Hematopoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Heart Arrest
Platelet Count
Peripheral Blood Stem Cells
Sepsis
Neutrophils
Heart Failure
Kidney
Lung
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer. / Patnaik, Amita; MacKinnon, Janet; Goss, Paul; Nagy, Tracy; Stewart, Alexander Keith; Keating, Armand; Crump, Michael.

In: Journal of Clinical Oncology, Vol. 18, No. 12, 06.2000, p. 2363-2368.

Research output: Contribution to journalArticle

@article{928a1925371c4902839112992e747e7b,
title = "Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer",
abstract = "Purpose: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high Complete and overall response rates in metastatic breast cancer (MBC). Patients and Methods: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline- based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m2/d and mitoxantrone 16 mg/m2/d combined with escalating doses of carboplatin 200 to 500 mg/m2/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 μg/d subcutaneously starting on day 1. Results: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with ≤ 400 mg/m2 of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 109/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 109/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). Conclusion: The maximum-tolerated dose of carboplatin was 400 mg/m2/d in combination with mitoxantrone 16 mg/m2/d and cyclophosphamide 1,500 mg/m2, all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment. (C) 2000 by American Society of Clinical Oncology.",
author = "Amita Patnaik and Janet MacKinnon and Paul Goss and Tracy Nagy and Stewart, {Alexander Keith} and Armand Keating and Michael Crump",
year = "2000",
month = "6",
language = "English (US)",
volume = "18",
pages = "2363--2368",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "12",

}

TY - JOUR

T1 - Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer

AU - Patnaik, Amita

AU - MacKinnon, Janet

AU - Goss, Paul

AU - Nagy, Tracy

AU - Stewart, Alexander Keith

AU - Keating, Armand

AU - Crump, Michael

PY - 2000/6

Y1 - 2000/6

N2 - Purpose: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high Complete and overall response rates in metastatic breast cancer (MBC). Patients and Methods: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline- based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m2/d and mitoxantrone 16 mg/m2/d combined with escalating doses of carboplatin 200 to 500 mg/m2/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 μg/d subcutaneously starting on day 1. Results: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with ≤ 400 mg/m2 of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 109/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 109/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). Conclusion: The maximum-tolerated dose of carboplatin was 400 mg/m2/d in combination with mitoxantrone 16 mg/m2/d and cyclophosphamide 1,500 mg/m2, all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment. (C) 2000 by American Society of Clinical Oncology.

AB - Purpose: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high Complete and overall response rates in metastatic breast cancer (MBC). Patients and Methods: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline- based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m2/d and mitoxantrone 16 mg/m2/d combined with escalating doses of carboplatin 200 to 500 mg/m2/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 μg/d subcutaneously starting on day 1. Results: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with ≤ 400 mg/m2 of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 109/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 109/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). Conclusion: The maximum-tolerated dose of carboplatin was 400 mg/m2/d in combination with mitoxantrone 16 mg/m2/d and cyclophosphamide 1,500 mg/m2, all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment. (C) 2000 by American Society of Clinical Oncology.

UR - http://www.scopus.com/inward/record.url?scp=0034126558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034126558&partnerID=8YFLogxK

M3 - Article

C2 - 10856095

AN - SCOPUS:0034126558

VL - 18

SP - 2363

EP - 2368

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 12

ER -