International Journal of Clinical Oncology

, Volume 20, Issue 3, pp 474–479 | Cite as

A phase I study of combination therapy with nanoparticle albumin-bound paclitaxel and cyclophosphamide in patients with metastatic or recurrent breast cancer

  • Goro Kutomi
  • Tousei Ohmura
  • Fukino Satomi
  • Hideki Maeda
  • Hiroaki Shima
  • Hidekazu Kameshima
  • Minoru Okazaki
  • Hideji Masuoka
  • Kenichi Sasaki
  • Koichi Hirata
Original Article



The objective of the present clinical study is to determine the maximum tolerated dose (MTD)/recommended dose (RD) of combination therapy with nanoparticle albumin-bound paclitaxel (nab-PTX) and cyclophosphamide (CPA) in patients with metastatic or recurrent breast cancer.


nab-PTX and CPA were administered on the first day of each 21-day treatment cycle. The dose of CPA was fixed at 600 mg/m2, while the dose of nab-PTX was increased from 180 mg/m2 (Level 1) to 220 mg/m2 (Level 2) and then to 260 mg/m2 (Level 3).


A total of 11 patients from two institutions were enrolled in the present study. At Level 3, a dose-limiting toxicity (DLT) was observed in 1 patient. Considering treatment continuity and the risk of adverse events in Cycle 2 and thereafter at this level, further subject enrollment at Level 3 was discontinued after two patients had been enrolled.

Since the doses used at Level 3 were considered the MTD of nab-PTX and CPA and the doses used at Level 2 were considered the RD of nab-PTX and CPA, three additional subjects were enrolled at Level 2. No DLTs were observed at Level 2.


The RD of combination therapy with nab-PTX and CPA was 220 mg/m2 and 600 mg/m2, respectively, in patients with metastatic or recurrent breast cancer.


Breast cancer nab-paclitaxel Cyclophosphamide Phase I 


Conflict of interest

All authors declare no conflicts of interest.


  1. 1.
    Hortobagyi GN (1998) Treatment of breast cancer. N Engl J Med 339:974–984PubMedCrossRefGoogle Scholar
  2. 2.
    The Japanese Breast Cancer Society (2013) Breast cancer guideline. Kanehara & Co. Ltd, TokyoGoogle Scholar
  3. 3.
    Von Hoff DD, Layard MW, Basa P et al (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717CrossRefGoogle Scholar
  4. 4.
    Bissery MC, Vrignaud P, Lavelle F (1995) Preclinical profile of docetaxel (taxotere): efficacy as a single agent and in combination. Semin Oncol 22:3–16Google Scholar
  5. 5.
    Jonathan CTr, Vicente V, Daniel JB et al (2003) A phase I study of docetaxel plus cyclophosphamide in solid tumors followed by a phase II study as first-line therapy in metastatic breast cancer. Clin Cancer Res 9:2426–2434Google Scholar
  6. 6.
    Stephen EJ, Michael AS, Frankie H et al (2006) A phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 34:5381–5387Google Scholar
  7. 7.
    Gradishar WJ (2006) Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother 7:1041–1053PubMedCrossRefGoogle Scholar
  8. 8.
    Ibrahim NK, Desai N, Legha S et al (2002) Phase I and pharmacokinetic study of ABI-007, a Cremophor-free protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 8:1038–1044PubMedGoogle Scholar
  9. 9.
    Ibrahim NK, Samuels B, Page R et al (2005) Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J Clin Oncol 23:6019–6026PubMedCrossRefGoogle Scholar
  10. 10.
    Gradishar WJ, Tjulandin S, Davidson N et al (2005) Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 23:7794–7803PubMedCrossRefGoogle Scholar
  11. 11.
    William JG, Dimitry K, Sergey C et al (2009) Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 27:3611–3619CrossRefGoogle Scholar
  12. 12.
    Desai N, Trieu V, Yao Z et al (2006) Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 12:1317–1324PubMedCrossRefGoogle Scholar
  13. 13.
    Sparreboom A, van Zuylen L, Brouwer E et al (1999) Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res 59:1454–1457PubMedGoogle Scholar
  14. 14.
    John TA, Vogel SM, Tiruppathi C et al (2003) Quantitative analysis of albumin uptake and transport in the rat microvessel endothelial monolayer. Am J Physiol Lung Cell Mol Physiol 284:187–196CrossRefGoogle Scholar
  15. 15.
    Elsadek B, Kratz F (2012) Impact of albumin on drug delivery−new applications on the horizon. J Control Release 157:4–28PubMedCrossRefGoogle Scholar
  16. 16.
    Denise Y, Howard B, Nancy P et al (2010) A pilot study of adjuvant nanoparticle albumin-bound (nab) paclitaxel and cyclophosphamide with trastuzumab in HER2-positive patients, in the treatment of early-stage breast cancer. Breast Cancer Res Treat 123:471–475CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2014

Authors and Affiliations

  • Goro Kutomi
    • 1
  • Tousei Ohmura
    • 2
  • Fukino Satomi
    • 1
  • Hideki Maeda
    • 1
  • Hiroaki Shima
    • 1
  • Hidekazu Kameshima
    • 2
  • Minoru Okazaki
    • 3
  • Hideji Masuoka
    • 4
  • Kenichi Sasaki
    • 5
  • Koichi Hirata
    • 1
  1. 1.Department of Surgery, Surgical Oncology and Science, School of MedicineSapporo Medical UniversitySapporoJapan
  2. 2.Department of SurgeryHigashi-Sapporo HospitalSapporoJapan
  3. 3.Sapporo Breast Surgical ClinicSapporoJapan
  4. 4.Sapporo-Kotoni Breast ClinicSapporoJapan
  5. 5.Department of SurgeryMuroran City General HospitalMuroranJapan

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