Journal of Clinical Oncology, Vol 14, 783-791, Copyright © 1996 by American Society of Clinical Oncology
Phase I and pharmacologic study of sequences of paclitaxel and cyclophosphamide supported by granulocyte colony-stimulating factor in women with previously treated metastatic breast cancer
MJ Kennedy, ML Zahurak, RC Donehower, DA Noe, S Sartorius, TL Chen, K Bowling and EK Rowinsky
The Johns Hopkins Oncology Center, Baltimore, MD, 21287, USA.
PURPOSE: Pacltaxel is active in metastatic breast cancer, but limited
information is available on combinations of this agent with other cytotoxic
agents. Study aims were to determine the maximum-tolerated doses (MTDs) of
paclitaxel (24-hour infusion) and cyclophosphamide (1- hour infusion)
administered every 21 days with granulocyte colony- stimulating factor
(G-CSF, filgrastim) to determine the effect of drug sequence on toxicity
and pharmacology and to evaluate the activity of this combination in women
with anthracycline-resistant disease. PATIENTS AND METHODS: Thirty-seven
women with metastatic breast cancer were treated. Starting doses were
paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2, with filgrastim 5
microG/kg/d subcutaneously beginning 24 hours after chemotherapy. Four
patients were treated at each dose level. The sequence of drug
administration was alternated between sequential patients, and with
subsequent courses of therapy in each patient, to enable evaluation of
effects of drug sequence on toxicity and pharmacology. Patients were
treated every 21 days and disease status was reevaluated every two courses.
RESULTS: Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 is the MTD
for this combination on this schedule. The hematopoietic toxicity of
therapy was sequence-dependent. Paired analysis of toxicity data indicated
more severe toxicity in courses in which paclitaxel was administered first.
Sequence-dependent pharmacologic effects did not account for this
phenomenon. Responses were noted in 29% of patients with
anthracycline-resistant disease. CONCLUSION: Paclitaxel 200 mg/m2 and
cyclophosphamide 1,250 mg/m2 with filgrastim administered every 21 days are
the doses recommended for further study.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
J. C. Trent, V. Valero, D. J. Booser, L. T. Esparza-Guerra, N. Ibrahim, Z. Rahman, L. Vernillet, S. Patel, C. L. David, J. L. Murray, et al.
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.,
July 1, 2003;
9(7):
2426 - 2434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S H Lam and R. J Ignoffo
A guide to clinically relevant drug interactions in oncology
Journal of Oncology Pharmacy Practice,
June 1, 2003;
9(2-3):
45 - 85.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Kurata, T. Tamura, T. Shinkai, Y. Ohe, H. Kunitoh, T. Kodama, R. Kakinuma, T. Matsumoto, K. Kubota, H. Omatsu, et al.
Phase I and Pharmacological Study of Paclitaxel Given Over 3 h with Cisplatin for Advanced Non-small Cell Lung Cancer
Jpn. J. Clin. Oncol.,
March 1, 2001;
31(3):
93 - 99.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Itoh, Y. Sasaki, H. Fujii, H. Minami, T. Ohtsu, H. Wakita, T. Igarashi, Y. Watanabe, Y. Onozawa, M. Kashimura, et al.
Study of Dose Escalation and Sequence Switching of Administration of the Combination of Docetaxel and Doxorubicin in Advanced Breast Cancer
Clin. Cancer Res.,
October 1, 2000;
6(10):
4082 - 4090.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. A. Perez
Paclitaxel in Breast Cancer
Oncologist,
December 1, 1998;
3(6):
373 - 389.
[Abstract]
[Full Text]
|
|
|
|
