Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer

Henderson, I. Craig; Berry, Donald A.; Demetri, George D.; Cirrincione, Constance; Goldstein, Lori J.; Martino, Silvana; Ingle, James N.; Cooper, M. Robert; Hayes, Daniel F.; Tkaczuk, Katherine H.; Fleming, Gini F.; Holland, James F.; Duggan, David B.; Carpenter, John T.; Frei, Emil; Schilsky, Richard L.; Wood, William C.; Muss, Hyman B.; Norton, Larry

doi:10.1200/jco.2003.02.063

Cited by 1,241 publications

(737 citation statements)

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“…Furthermore, our results need to be discussed in front of the recent introduction of taxanes in the adjuvant treatment of EBC. Indeed, recent studies have clearly demonstrated a benefit in term of MFS and OS when paclitaxel or docetaxel are associated with anthracylines in chemotherapy regimen administered after primary surgery of EBC patients with lymph node invasion (Henderson et al, 2003;Nabholtz et al, 2002). However, the taxane-anthracycline combination, although effective is probably more toxic and certainly more expensive, justifying efforts to identify patients likely to be cured by conventional anthracycline-based regimen alone.…”

Section: Discussionmentioning

confidence: 99%

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

et al. 2005

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A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; Po0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.

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Section: Discussionmentioning

confidence: 99%

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

et al. 2005

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“…Based on their significant activity in the metastatic setting [2], the taxanes have also been extensively tested in the adjuvant setting in many randomized trials [3][4][5][6][7][8]; significant improvement in efficacy outcomes in terms of disease-free survival (DFS) [4,5] and overall survival (OS) [3,6,7] has been reported. Moreover, recently, a meta-analysis of 13 randomized studies including 22,903 patients demonstrated that the addition of a taxane to an anthracycline-based regimen improves DFS and OS of high-risk early breast cancer patients [9].…”

Section: Introductionmentioning

confidence: 99%

FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG)

Polyzos

Malamos²,

Boukovinas

et al. 2009

Breast Cancer Res Treat

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International audienceA randomized multicenter phase III study was conducted to compare the sequential docetaxel followed by epirubicin/cyclophosphamide combination with that of FEC regimen as adjuvant chemotherapy in women with axillary node-positive early breast cancer. Seven hundred and fifty-six women with axillary lymph node-positive breast cancer were randomized to receive either 4 cycles of docetaxel (100 mg/m) followed by 4 cycles of epirubicin (75 mg/m) plus cyclophosphamide (700 mg/m) (experimental arm) or 6 cycles of FEC (epirubicin 75 mg/m, cyclophosphamide 700 mg/m, and 5-fluorouracil 700 mg/m; control arm). All regimes were administered every 3 weeks. The primary end point was five-year disease-free survival (DFS). After a median follow-up period of 5 years, 233 (30.8%) relapses had occurred (108 and 125 in the experimental and control arms, respectively; = 0.181). The five-year DFS was 72.6% (95% CI 63.8–81.3%) and 67.2% (95% CI 58.0–76.4%) for women randomized in the experimental and control arms, respectively ( = 0.041; log rank test). There was no difference in the overall survival between the two arms (83.8 and 81.4% in the experimental and control arms, respectively; = 0.533). The experimental arm was associated with increased neutropenia requiring administration of granulocyte colony-stimulating factor in 90.5% of the patients as compared with 74.1% in the control arm ( = 0.0001). The sequential docetaxel followed by epirubicin/cyclophosphamide adjuvant chemotherapy regimen resulted in improved five-year DFS in women with axillary node-positive early breast cancer at the expense of increased but manageable myelotoxicity

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“…1 to receive eight cycles of FAC vs. four cycles of paclitaxel followed by four cycles of FAC. 6 The question posed by this trial was whether the initial positive results reported with the addition of paclitaxel to an anthracycline-based regimen 5 were the result of merely more chemotherapy as opposed to a specific therapeutic effect of paclitaxel. Preliminary results demonstrated a trend toward prolonged DFS at a median follow-up of 4years (83% for FAC ϫ8 vs. 86% for paclitaxel ϫ4 followed by FAC ϫ4), which did not reach statistical significance (P ϭ 0.09).…”

Section: Discussionmentioning

confidence: 99%

A Phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma

Assikis

Buzdar

Yang

et al. 2003

Cancer

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BACKGROUNDThe current study was performed to assess whether sequential potentially noncross‐resistant chemotherapy prolongs disease‐free survival (DFS) and overall survival (OS) in patients with operable breast carcinoma.METHODSSeven hundred eighty‐nine patients were registered and followed for a median of 10 years. They were treated in two groups. In Group 1, patients age < 50 years or age > 50 years but with either negative or unknown estrogen receptor (ER) status were randomized to receive 6 cycles of 5‐fluorouracil, doxorubicin, and cyclophosphamide (FAC) alone or followed by 4 cycles of methotrexate and vinblastine (MV). In Group 2, patients age ≥ 50 years with ER‐positive disease were randomized to receive either tamoxifen or combination chemotherapy (FAC + MV) for 10 cycles. Analysis was performed according to allocated treatment (intention to treat), with all randomized patients included.RESULTSIn Group 1 there were no significant differences with regard to DFS or OS between the two treatment arms. The DFS at 5 years was 0.70 and 0.76, respectively, for FAC compared with FAC+MV (P = 0.26). The OS was similar for both groups (0.84 vs. 0.83). It is interesting to note that there was a statistically nonsignificant trend for improved DFS in the FAC + MV arm for patients who were ER‐positive. In Group 2, tamoxifen alone led to more prolonged DFS compared to FAC+MV (0.78 vs. 0.66, respectively) but this did not reach statistical significance (P = 0.28). OS also was associated with a trend (P = 0.86) toward prolonged survival for the tamoxifen arm compared with the FAC+MV arm (0.85 vs. 0.74, respectively).CONCLUSIONSThe results of the current trial concerning sequential adjuvant chemotherapy for operable breast carcinoma, which to our knowledge contains the longest follow‐up presented to date, failed to demonstrate any additional benefit from the addition of 4 cycles of MV to 6 cycles of FAC chemotherapy. Cancer 2003;97:2716–23. © 2003 American Cancer Society.DOI 10.1002/cncr.11396

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Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer

Abstract: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

Cited by 1,241 publications

References 19 publications

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG)

A Phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma

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