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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

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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)
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)
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)
Taxol: Mechanisms of Action and Resistance a
S. Horwitz (1993)
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)
Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.
J. Liebmann (1993)
Successful re-treatment with taxol after major hypersensitivity reactions.
D. Peereboom (1993)
Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer.
F. Holmes (1991)
Cardiac disturbances during the administration of taxol.
E. Rowinsky (1991)
Taxol in combination with doxorubicin or etoposide possible antagonism in vitro
S. Hahn (1993)
Adriamycin therapy by continuous intravenous infusion in patients with metastatic breast cancer
S. Legha (1982)
P‐glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines
G. M. Lai (1991)
Taxol toxicity. Epithelial necrosis in the gastrointestinal tract associated with polymerized microtubule accumulation and mitotic arrest
R. H. Hruban (1989)
Typhlitis resulting from treatment with taxol and doxorubicin in patients with metastatic breast cancer
B. Pestalozzi (1993)
Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer.
E. Kohn (1994)
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)
Modulation by verapamil of vincristine pharmacokinetics and toxicity in mice bearing human tumor xenografts.
J. Horton (1989)
Pharmacokinetics of taxol and doxorubicin administered alone and in combination by continuous 72-hour infusion.
S. Berg (1994)
A phase I-II study of intensive-dose adriamycin for advanced breast cancer.
R. Jones (1987)
Estimation of doxorubicin and doxorubicinol by high-performance liquid chromatography and advanced automated sample processor.
N. Dobbs (1987)
Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96-hour infusion.
W. Wilson (1994)
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
New developments in chemotherapy of advanced breast cancer.
D. Lebwohl (1999)
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)
Paclitaxel induces significant changes in epidoxorubicin distribution in mice.
T. Colombo (1996)
Dose-intensified chemotherapy for breast cancer: Present and future prospects
T. Tajima (1998)
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)
Taxanes in the treatment of breast cancer: a prodigy comes of age.
K. Miller (1999)
Review : Pharmacokinetics and pharmacodynamics of the taxanes
Y. F. Lam (1997)
Putting the taxanes to work: unanswered questions.
P. Conte (1998)
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)
Taxane/anthracycline combinations: setting a new standard in breast cancer?
J. Nabholtz (2001)
Sequential Administration of Doxorubicin and Paclitaxel Followed by Cyclophosphamide, Methotrexate and 5-Fluorouracil Combination (CMF) in Women with Metastatic Breast Cancer
C. Papadimitriou (1998)
Chemotherapy of breast cancer: are the taxanes going to change the natural history of breast cancer?
J. Nabholtz (2000)
Paclitaxel and Mitoxantrone in the Treatment of Metastatic Breast Cancer: A Phase II Trial of the Minnie Pearl Cancer Research Network
J. Hainsworth (2002)
Joyce Ann O'Shaughnessy, MD: A Conversation with the Editor
J. O'Shaughnessy (2004)
Dose-finding study of docetaxel and doxorubicin in first-line treatment of patients with metastatic breast cancer.
J. L. Misset (1999)
Front-line treatment of advanced breast cancer with docetaxel and epirubicin: a multicenter phase II study.
D. Mavroudis (2000)
The role of taxanes in the treatment of breast cancer
J. Nabholtz (2005)
Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: phase I results.
F. Holmes (1999)
Cardiac function following combination therapy with paclitaxel and doxorubicin: an analysis of 657 women with advanced breast cancer.
L. Gianni (2001)
Combination versus sequential single-agent therapy in metastatic breast cancer.
D. Miles (2002)
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)
Aneugenic and clastogenic effects of doxorubicin in human lymphocytes.
A. Dhawan (2003)
Breast Cancer Therapies in Development
Dominique de Valeriola (2012)
Typhlitis associated with docetaxel treatment.
F. Cardenal (1996)
Automatic breast cancer cell classification using deep convolutional neural networks
G. Pattarone (2020)
Risks and Benefits of Taxanes in Breast and Ovarian Cancer
L. Michaud (2000)
Doxorubicin-Docetaxel Sequential Schedule: Results of Front-Line Treatment in Advanced Breast Cancer
S. Palmeri (2002)
Metronomic doses and drug schematic combination response tested within microfluidic models for the treatment of breast cancer cells (JIMT-1)
G. Rosero (2020)
A Southwest Oncology Group Randomized Phase II Study of Doxorubicin and Paclitaxel as Frontline Chemotherapy for Women with Metastatic Breast Cancer
G. Lyman (2004)
Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review
T. Stage (2017)
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