Abstract | PURPOSE: PATIENTS AND METHODS: Female patients with early-stage, node-positive invasive breast cancer were eligible for this multicenter, cooperative group feasibility trial that was designed as the pilot study for a larger randomized clinical trial. The protocol treatment comprised five cycles of dose-intensified AC (75 and 2000 mg/m(2)/cycle, respectively, intravenously every three weeks) with G-CSF support, followed by an additional four cycles of T (175 mg/m(2) by 3h intravenous infusion, every three weeks). Patients were randomized to receive one of two dose levels of G-CSF (5 vs. 10 mcg/kg/day) during AC chemotherapy. Data on both short-term toxicity and long-term survival were collected. RESULTS: One hundred and seventy two node-positive patients with operable primary breast cancer were accrued to this trial between February 1993 and April 1994. 130 of the 172 patients (76%) completed all protocol-specified therapy. Of the 42 early study withdrawals, 23 were due to unacceptable acute treatment-related toxicity. No differences in toxicities or clinical outcomes were noted between the two different dose levels of G-CSF support. At 6.8 years median follow-up, relapse-free survival (RFS) and overall survival (OS) rates for all patients are 70% and 78%, respectively. Ten patients developed second malignancies during follow-up, including three cases with a hematologic malignancy (2% incidence). CONCLUSION: The delivery of dose-intensified AC followed by T was feasible in this large-scale pilot trial, although significant acute toxicities were commonly encountered. The data confirmed the acceptable tolerability of T after aggressive myelotoxic therapy in the adjuvant setting, leading to a larger randomized clinical trial comparing three dose levels of doxorubicin in AC with or without the addition of T (CALGB 9344). Supportive care using twice the conventional dose of G-CSF did not significantly improve the tolerability or change the toxicities of this regimen, and the occurrence of secondary malignancies is consistent with the emerging risk profile of dose-intensive regimens with growth factor support. With long-term follow-up, the clinical outcomes remain relatively favorable and correlate with such expected prognostic factors as the number of involved nodes and hormone receptor status.
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Authors | Minetta C Liu, George D Demetri, Donald A Berry, Larry Norton, Gloria Broadwater, Nicholas J Robert, David Duggan, Daniel F Hayes, I Craig Henderson, Alan Lyss, Judith Hopkins, Peter A Kaufman, P Kelly Marcom, Jerry Younger, Nancy Lin, Katherine Tkaczuk, Eric P Winer, Clifford A Hudis, Cancer and Leukemia Group B |
Journal | Cancer treatment reviews
(Cancer Treat Rev)
Vol. 34
Issue 3
Pg. 223-30
(May 2008)
ISSN: 0305-7372 [Print] Netherlands |
PMID | 18234424
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Recombinant Proteins
- Granulocyte Colony-Stimulating Factor
- Doxorubicin
- Cyclophosphamide
- Paclitaxel
- Filgrastim
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Topics |
- Adult
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, adverse effects)
- Breast Neoplasms
(drug therapy, mortality, pathology)
- Chemotherapy, Adjuvant
(methods)
- Cyclophosphamide
(administration & dosage)
- Disease-Free Survival
- Doxorubicin
(administration & dosage)
- Female
- Filgrastim
- Follow-Up Studies
- Granulocyte Colony-Stimulating Factor
(administration & dosage)
- Humans
- Lymphatic Metastasis
- Middle Aged
- Paclitaxel
(administration & dosage)
- Pilot Projects
- Recombinant Proteins
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