Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Phase I/II Study Of 72-hour Infusional Paclitaxel And Doxorubicin With Granulocyte Colony-stimulating Factor In Patients With Metastatic Breast Cancer.

J. Fisherman, K. Cowan, M. Noone, A. Denicoff, S. Berg, D. Poplack, F. Balis, D. Venzon, M. McCabe, B. Goldspiel, C. Chow, F. Ognibene, J. O'Shaughnessy
Published 1996 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
PURPOSE We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.
This paper references
Cross-resistance of vinblastine- and taxol-resistant mutants of Chinese hamster ovary cells to other anticancer drugs.
R. Gupta (1985)
10.1016/0360-3016(90)90019-G
In vitro effect of doxorubicin on non-proliferating and proliferating epithelial cells.
E. Baral (1990)
Use of growth-stimulatory hormones to improve the in vitro therapeutic index of doxorubicin for human breast tumors.
V. Hug (1986)
Taxol in Combination with Doxorubicin or Etoposide
S. Hahn (1993)
10.1093/OXFORDJOURNALS.ANNONC.A058975
A dose intensity study of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy and Escherichia coli-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) in advanced breast cancer patients.
J. O'Shaughnessy (1994)
10.1111/j.1749-6632.1986.tb38455.x
Taxol: Mechanisms of Action and Resistance a
S. Horwitz (1993)
10.1016/0277-5379(89)90135-1
Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy.
S. Bielack (1989)
Paclitaxel (Taxol)/doxorubicin combinations in advanced breast cancer: the Eastern Cooperative Oncology Group experience.
G. Sledge (1994)
10.1038/bjc.1993.488
Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.
J. Liebmann (1993)
10.1200/JCO.1993.11.5.885
Successful re-treatment with taxol after major hypersensitivity reactions.
D. Peereboom (1993)
10.1093/JNCI/83.24.1797
Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer.
F. Holmes (1991)
10.1200/JCO.1991.9.9.1704
Cardiac disturbances during the administration of taxol.
E. Rowinsky (1991)
10.1002/1097-0142(19931101)72:9<2705::AID-CNCR2820720930>3.0.CO;2-K
Taxol in combination with doxorubicin or etoposide possible antagonism in vitro
S. Hahn (1993)
10.1002/1097-0142(19820501)49:9<1762::AID-CNCR2820490905>3.0.CO;2-Q
Adriamycin therapy by continuous intravenous infusion in patients with metastatic breast cancer
S. Legha (1982)
10.1002/IJC.2910490512
P‐glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines
G. M. Lai (1991)
10.1002/1097-0142(19890515)63:10<1944::AID-CNCR2820631013>3.0.CO;2-#
Taxol toxicity. Epithelial necrosis in the gastrointestinal tract associated with polymerized microtubule accumulation and mitotic arrest
R. H. Hruban (1989)
10.1002/1097-0142(19930301)71:5<1797::AID-CNCR2820710514>3.0.CO;2-B
Typhlitis resulting from treatment with taxol and doxorubicin in patients with metastatic breast cancer
B. Pestalozzi (1993)
10.1093/JNCI/86.1.18
Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer.
E. Kohn (1994)
10.1200/JCO.1993.11.10.1943
Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer.
B. Reichman (1993)
Taxol-based combination chemotherapy and other in vivo preclinical antitumor studies.
Rose Wc (1993)
10.1016/0006-2952(89)90405-X
Modulation by verapamil of vincristine pharmacokinetics and toxicity in mice bearing human tumor xenografts.
J. Horton (1989)
10.1093/JNCI/86.2.143
Pharmacokinetics of taxol and doxorubicin administered alone and in combination by continuous 72-hour infusion.
S. Berg (1994)
10.1200/JCO.1987.5.2.172
A phase I-II study of intensive-dose adriamycin for advanced breast cancer.
R. Jones (1987)
10.1016/0378-4347(87)80171-8
Estimation of doxorubicin and doxorubicinol by high-performance liquid chromatography and advanced automated sample processor.
N. Dobbs (1987)
10.1200/JCO.1994.12.8.1621
Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96-hour infusion.
W. Wilson (1994)
10.1200/JCO.1995.13.11.2688
Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study.
L. Gianni (1995)



This paper is referenced by
10.1093/ANNONC/10.SUPPL_6.S139
New developments in chemotherapy of advanced breast cancer.
D. Lebwohl (1999)
10.1177/030089160409000303
Design and Development of New Combinations of the CMF Agents with Taxanes (Paclitaxel or Docetaxel) in Advanced Breast Cancer: A Feasibility Study
G. Cocconi (2004)
10.1093/OXFORDJOURNALS.ANNONC.A010758
Paclitaxel induces significant changes in epidoxorubicin distribution in mice.
T. Colombo (1996)
10.1007/BF02967411
Dose-intensified chemotherapy for breast cancer: Present and future prospects
T. Tajima (1998)
10.1097/01.coc.0000217552.69036.16
Phase I-II Study of Pegylated Liposomal Doxorubicin Combined With Weekly Paclitaxel as First-Line Treatment in Patients With Metastatic Breast Cancer
H. Bourgeois (2006)
10.1080/07357909909011727
Taxanes in the treatment of breast cancer: a prodigy comes of age.
K. Miller (1999)
10.1177/107815529700300202
Review : Pharmacokinetics and pharmacodynamics of the taxanes
Y. F. Lam (1997)
10.1007/978-3-642-45769-2_29
Putting the taxanes to work: unanswered questions.
P. Conte (1998)
10.1046/J.1365-2125.2002.01579.X
Pharmacokinetics and pharmacodynamics of combination chemotherapy with paclitaxel and epirubicin in breast cancer patients.
R. Danesi (2002)
Paclitaxel for breast cancer: the Memorial Sloan-Kettering Cancer Center experience.
A. Seidman (1997)
10.1634/THEONCOLOGIST.6-SUPPL_3-5
Taxane/anthracycline combinations: setting a new standard in breast cancer?
J. Nabholtz (2001)
10.1159/000011908
Sequential Administration of Doxorubicin and Paclitaxel Followed by Cyclophosphamide, Methotrexate and 5-Fluorouracil Combination (CMF) in Women with Metastatic Breast Cancer
C. Papadimitriou (1998)
10.1517/14656566.1.2.187
Chemotherapy of breast cancer: are the taxanes going to change the natural history of breast cancer?
J. Nabholtz (2000)
10.1081/CNV-120005897
Paclitaxel and Mitoxantrone in the Treatment of Metastatic Breast Cancer: A Phase II Trial of the Minnie Pearl Cancer Research Network
J. Hainsworth (2002)
10.1080/08998280.2004.11927967
Joyce Ann O'Shaughnessy, MD: A Conversation with the Editor
J. O'Shaughnessy (2004)
10.1023/A:1026418831238
Dose-finding study of docetaxel and doxorubicin in first-line treatment of patients with metastatic breast cancer.
J. L. Misset (1999)
10.1023/a:1008351310818
Front-line treatment of advanced breast cancer with docetaxel and epirubicin: a multicenter phase II study.
D. Mavroudis (2000)
10.1517/14656566.6.7.1073
The role of taxanes in the treatment of breast cancer
J. Nabholtz (2005)
10.1023/A:1008360406322
Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: phase I results.
F. Holmes (1999)
10.1023/A:1011655503511
Cardiac function following combination therapy with paclitaxel and doxorubicin: an analysis of 657 women with advanced breast cancer.
L. Gianni (2001)
10.1634/THEONCOLOGIST.8-1-124
Combination versus sequential single-agent therapy in metastatic breast cancer.
D. Miles (2002)
10.1093/JNCI/89.13.917
Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance.
B. Trock (1997)
Paclitaxel plus epirubicin in advanced breast cancer.
P. Conte (1998)
10.1093/MUTAGE/GEG024
Aneugenic and clastogenic effects of doxorubicin in human lymphocytes.
A. Dhawan (2003)
10.2165/00003495-199754030-00003
Breast Cancer Therapies in Development
Dominique de Valeriola (2012)
10.1093/JNCI/88.15.1078
Typhlitis associated with docetaxel treatment.
F. Cardenal (1996)
10.17160/josha.7.2.652
Automatic breast cancer cell classification using deep convolutional neural networks
G. Pattarone (2020)
10.2165/00002018-200023050-00005
Risks and Benefits of Taxanes in Breast and Ovarian Cancer
L. Michaud (2000)
10.1159/000065466
Doxorubicin-Docetaxel Sequential Schedule: Results of Front-Line Treatment in Advanced Breast Cancer
S. Palmeri (2002)
10.1101/2020.07.16.188748
Metronomic doses and drug schematic combination response tested within microfluidic models for the treatment of breast cancer cells (JIMT-1)
G. Rosero (2020)
10.1023/B:BREA.0000025405.63953.f9
A Southwest Oncology Group Randomized Phase II Study of Doxorubicin and Paclitaxel as Frontline Chemotherapy for Women with Metastatic Breast Cancer
G. Lyman (2004)
10.1007/s40262-017-0563-z
Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review
T. Stage (2017)
See more
Semantic Scholar Logo Some data provided by SemanticScholar