Dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in HER2/neu-overexpressed/amplified breast cancer is not feasible because of excessive diarrhea Journal Article


Authors: Dang, C.; Lin, N.; Moy, B.; Come, S.; Sugarman, S.; Morris, P.; Abbruzzi, A.; Chen, C.; Steingart, R.; Patil, S.; Norton, L.; Winer, E.; Hudis, C.
Article Title: Dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in HER2/neu-overexpressed/amplified breast cancer is not feasible because of excessive diarrhea
Abstract: Purpose: Dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel and trastuzumab (PT) is feasible. Lapatinib is effective in the treatment of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer. We conducted a pilot study of dose-dense AC followed by PT plus lapatinib (PTL) followed by trastuzumab plus lapatinib (TL). Patients and Methods: Patients with stages I to III, HER2-positive breast cancer and left ventricular ejection fraction (LVEF) of ≥ 50% were enrolled. Treatment consisted of AC (60 mg/m2 and 600 mg/m2) for 4 cycles every 2 weeks (with pegfilgrastim 6 mg on day 2) followed by paclitaxel (80 mg/m2) for 12 doses weekly plus trastuzumab and lapatinib. Trastuzumab (4 mg/kg loading dose, then 2 mg/kg weekly during paclitaxel then 6 mg/kg every 3 weeks after paclitaxel) and lapatinib (1,000 mg daily) were given for 1 year. The primary end points were feasibility defined as ≥ 80% patients completing the PTL phase without a dose delay/reduction and a cardiac event rate of ≤ 4%. Results: From March 2007 to April 2008, we enrolled 95 patients. Median age was 46 years (range, 28 to 73 years). At a median follow-up of 22 months, 92 were evaluable. Of the 92 patients, 41 patients (45%) withdrew for PTL-specific toxicities. Overall, 40 (43%) of 92 patients had lapatinib dose reductions, and 27 (29%) of 92 patients had grade 3 diarrhea. Three patients (3%) had congestive heart failure; three patients dropped out because of significant asymptomatic LVEF decline during PTL followed by TL. Conclusion: Dose-dense AC followed by PTL and then followed by TL was not feasible because of a high rate of lapatinib dose reduction, mostly caused by unacceptable grade 3 diarrhea. Lapatinib (1,000 mg/d) was not feasible combined with weekly PT. © 2010 by American Society of Clinical Oncology.
Keywords: adult; treatment outcome; treatment response; aged; middle aged; survival rate; major clinical study; genetics; clinical trial; constipation; fatigue; neutropenia; doxorubicin; diarrhea; dose response; drug dose reduction; drug withdrawal; side effect; paclitaxel; cancer staging; follow up; follow-up studies; antineoplastic agent; neoplasm staging; metabolism; in situ hybridization, fluorescence; gene overexpression; drug eruption; multiple cycle treatment; pain; phase 2 clinical trial; sensory neuropathy; neoplasm recurrence, local; breast cancer; gene amplification; anemia; leukopenia; mucosa inflammation; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; myalgia; qt prolongation; epidermal growth factor receptor 2; cyclophosphamide; pathology; dose-response relationship, drug; breast neoplasms; monoclonal antibody; arthralgia; dizziness; dyspnea; febrile neutropenia; fever; loading drug dose; pneumonia; enzyme immunoassay; immunoenzyme techniques; hospitalization; antibodies, monoclonal; fluorescence in situ hybridization; feasibility study; pilot study; feasibility studies; pilot projects; chemically induced disorder; tumor recurrence; breast tumor; acne; receptor, erbb-2; headache; trastuzumab; recombinant granulocyte colony stimulating factor; virus hepatitis; dyspepsia; heart left ventricle ejection fraction; quinazolines; congestive heart failure; lapatinib; quinazoline derivative; paronychia; cellulitis; filgrastim; acneiform; heart rate; skin pruritus
Journal Title: Journal of Clinical Oncology
Volume: 28
Issue: 18
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2010-06-20
Start Page: 2982
End Page: 2988
Language: English
DOI: 10.1200/jco.2009.26.5900
PUBMED: 20479410
PROVIDER: scopus
PMCID: PMC3664034
DOI/URL:
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 20 April 2011" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Sujata Patil
    383 Patil
  2. Patrick Glyn Morris
    107 Morris
  3. Clifford Hudis
    843 Hudis
  4. Larry Norton
    567 Norton
  5. Chau Dang
    156 Dang
  6. Richard M Steingart
    113 Steingart
  7. Carol Chen
    25 Chen