1 Northwestern University Feinberg School of Medicine, Chicago, IL; 2 Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, DHHS Bethesda, MD; 3 University of Tennessee Cancer Institute, Memphis, TN; 4 Tufts New England Medical Center, Boston, MA; 5 Carolinas-Hematology Oncology Associates and the Blumenthal Cancer Center, Charlotte, NC; 6 Aventis Pharmaceuticals, Bridgewater, NJ, USA
* Correspondence to: Dr S. M. Swain, Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, DHHS Bethesda, MD, USA. Tel: +1-301-651-6882; Fax: +1-301-496-0047; Email: swains{at}mail.nih.gov
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Patients and methods: Forty-five patients were planned to receive four cycles of docetaxel 100 mg/m2 every 3 weeks, followed by surgery, four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) every 3 weeks, radiation therapy (RT), and tamoxifen when indicated.
Results: After four cycles of neoadjuvant docetaxel, the clinical response rate within the breast was 59% (95% CI 42% to 73%) and overall (breast and axilla) was 49% (95% CI 38% to 72%) in the intention-to-treat (ITT) population. At the time of surgery, 10% (n=4) of patients had a pathologic complete response (pCR) in the breast, 27% (n=11) had a pCR within the axillary lymph nodes, and 7% (n=3) had a pCR in the breast and axilla (95% CI 2% to 21%). An additional 5% (n=2) had minimal residual invasive tumor (<5 mm). The 5-year overall survival rate was 80%. The percentage of patients with grade 3/4 neutropenia was similar during docetaxel (93%) and AC (86%), while a greater percentage of patients had febrile neutropenia during docetaxel treatment (27%) compared with AC treatment (7%).
Conclusions: Neoadjuvant docetaxel followed by surgery, adjuvant AC, hormonal therapy where indicated, and RT is an active regimen for patients with stage III breast cancer.
Key words: neoadjuvant docetaxel, stage II breast cancer
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 established that neoadjuvant treatment of operable early-stage breast cancer with four cycles of doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (AC) every 3 weeks had equivalent survival results when compared with the same regimen in the adjuvant setting [6, 7
]. Disease-free survival (DFS) and overall survival (OS) were similar in both groups, but breast conserving surgery was performed more frequently in those patients who received neoadjuvant chemotherapy. The clinical response rate (RR) for patients receiving neoadjuvant AC was 79%, with 36% having a clinical complete response (cCR). Thirteen per cent of patients with a cCR had a pathologic CR (pCR) in the breast only. At 9 years follow-up, patients with a pCR had higher DFS and OS rates than patients with residual invasive disease noted at the time of surgery [8
].
Docetaxel is one of the most active agents in the management of metastatic breast cancer [914
]. It has, therefore, been evaluated as part of sequential [15
21
] and combination regimens in phase II and III studies enrolling women with early stage breast cancer [5
, 15
, 18
, 20
25
]. These studies demonstrated that sequential administration of an anthracycline and docetaxel in the neoadjuvant setting result in clinical RRs and pCR rates ranging from 85% to 93% and 11% to 31%, respectively. For anthracycline and docetaxel combination treatment, clinical RRs and pCR rates ranging from 68% to 93% and 8% to 16%, respectively, have been reported.
The current study was conducted to evaluate the efficacy and safety of docetaxel as neoadjuvant, single agent chemotherapy for patients with stage III breast cancer. The overall survival of these patients following additional standard treatment with surgery, adjuvant chemotherapy and RT was also assessed.
![]() |
Patients and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Treatment
This was a multicenter, phase II study. Neoadjuvant therapy consisted of a 1-h intravenous infusion of docetaxel 100 mg/m2 every 3 weeks for a total of four cycles with dexamethasone premedication given as 8 mg twice daily for 5 days, beginning 24 h prior to treatment. Primary surgery with confirmation of negative margins was to be performed within 35 days after completion of neoadjuvant therapy. Adjuvant therapy with AC every 3 weeks for four cycles began within 1255 days after surgery. Tamoxifen was prescribed for 5 years for women aged less than 50 with estrogen receptor positive tumors and for all women 50 years of age, regardless of estrogen receptor status. Radiation therapy to the entire chest wall and supraclavicular area began within 4 weeks from the last cycle of AC. The breast was treated to >5000 cGy with conventional fractions of 180200 cGy/day. A boost was administered to the tumor excision site to bring the total dose to >6040 cGy. After completion of RT, clinical evaluations were performed every 3 months for 1 year and every 6 months thereafter. Patients were removed from the study if they developed tumor progression, were inoperable following four cycles of neoadjuvant docetaxel, experienced excessive toxicity, or withdrew consent.
Dose reductions of docetaxel to 75 mg/m2 and then 55 mg/m2, doxorubicin to 45 mg/m2 and then 35 mg/m2, and cyclophosphamide to 450 mg/m2 and then 350 mg/m2 were planned for grade 3/4 non-hematologic and grade 4 hematologic toxicities other than anemia. Prophylactic granulocyte colony-stimulating factor (G-CSF) was recommended for all subsequent chemotherapy cycles following an episode of febrile neutropenia or neutropenia lasting more than 7 days. Grade 3 neurotoxicity and grade 3/4 hypersensitivity reactions required discontinuation of docetaxel, while grade 1/2 hypersensitivity reactions or fluid retention were treated symptomatically.
Evaluation of response
Pretreatment tumor assessments, including a physical examination and radiological studies, were obtained within 3 weeks before registration. Clinical tumor assessment by palpation was performed prior to each cycle and radiographically after the fourth cycle of neoadjuvant docetaxel. Pathologic tumor assessments were performed at the time of surgery. After treatment, annual mammograms and clinically indicated imaging studies were performed.
Clinical response assessments were based on measurable bidimensional disease. Clinical responses were determined based on a comparison of pretreatment tumor measurements with those obtained after the final cycle of docetaxel. A cCR was defined as the disappearance of all known disease and a clinical partial response (cPR) represented a 50% or greater decrease in the sum of the areas of bidimensionally measured lesions. Progressive disease (PD) was defined as a 25% or greater increase in the area of any lesion greater than 2 cm2 or in the sum of the products of the individual lesions or the appearance of new malignant lesions. If the only measurable lesion were 2 cm2 at the start of neoadjuvant therapy, a 50% or greater increase in area was required for a determination of PD. Stable disease (SD) reflected no significant change in disease and no evidence of new disease. A pCR was defined as the complete absence of invasive tumor cells in the pathologic specimen. None of the patients who attained pCRs in this study had residual non-invasive disease.
All toxicities were evaluated using the NCI common toxicity criteria, version 1, except for peripheral edema, pleural and pericardial effusions, and ascites, which were graded as mild, moderate, or severe.
Statistical methods
The primary end point of this study was to assess overall objective response rate (complete response and partial response) after neoadjuvant docetaxel. The pCR rate at the time of surgery was a secondary end point. Based on response rates observed in phase II studies of docetaxel in patients with previously untreated metastatic breast cancer, the prestudy hypothesis assumed a clinical response rate of 58% for neoadjuvant administration of docetaxel. To achieve a lower limit of a 95% confidence interval (CI) for the true response rate of at least 41.5%, it was necessary to enroll 40 evaluable patients.
The intent-to-treat (ITT) population included all patients with stage III breast cancer enrolled in the study who received at least one cycle of neoadjuvant docetaxel. The evaluable population included all patients with stage III breast cancer who received at least one cycle of docetaxel and had at least one post-infusion tumor assessment. Demographics and safety findings are presented for all 45 enrolled patients. Efficacy findings are presented for both the ITT and the evaluable populations.
Overall survival was calculated from the date of study enrollment to the date of death; for patients who were alive, censoring occurred on the date of last contact or 15 December 2002, whichever was first.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
Exposure to study medication
During the neoadjuvant phase of the study, two patients had docetaxel dose reductions due to hematologic toxicities, four patients received reduced doses for non-hematologic toxicities, and one patient had the dose reduced for both hematologic and non-hematologic toxicities. The median relative dose intensity (RDI) for docetaxel was 0.99 (range 0.031.07). Dose reductions during the adjuvant phase were performed for one patient due to non-hematologic toxicity. The median RDIs for doxorubicin and cyclophosphamide were 1.00 (range 0.821.04) and 1.01 (range 0.831.04), respectively.
Response to therapy
As shown in Table 2, after four cycles of neoadjuvant docetaxel there was an overall RR (breast and axilla) of 49% (CR 7%; PR 42%; 95% CI 38% to 72%) and RR within the breast only of 59% (CR 15%; PR 44%; 95% CI 42% to 73%) for the ITT population. There were 36 patients evaluable for clinical response in the breast and axilla with an overall clinical response rate of 56% (CR 8%; PR 47%; 95% CI 41% to 74%). Five patients were non-evaluable for clinical response in the breast and axilla; in four cases, this was because follow-up lymph node measurements were not performed, and one patient was lost to follow-up. There were 39 patients evaluable for clinical response in the breast only with an overall clinical response rate of 62% (CR 15%; PR 46%; 95% CI 47% to 79%). Two patients were non-evaluable for clinical response in the breast only; one patient had node-only disease and one patient was lost to follow-up.
|
Patients were followed for a median of 5.6 years (range 0.57.6 years). Ten patients died due to breast cancer. Disease-free survival has not been included, as only limited data were available. Overall survival at 1 year for the ITT population was 95% (39 of 41 patients); for patients with stage IIIA and stage IIIB disease, 1-year overall survival rates were 100% and 91%, respectively. At 2 years, overall survival was 88%; for stage IIIA and IIIB patients, these rates were 95% and 82%, respectively. The 5-year overall survival was 80%; for stage IIIA and IIIB patients, these rates were 84% and 77%, respectively (Figure 2).
Safety
There were no deaths due to therapy while on study. As shown in Table 3, during neoadjuvant treatment with docetaxel, the most frequently reported grade 3/4 hematologic toxicity was neutropenia (93%), while anemia and thrombocytopenia were each reported for 2% of patients. During adjuvant treatment with AC, a similar incidence of grade 3/4 neutropenia (86%) was observed, but the rates of grade 3/4 anemia (14%) and thrombocytopenia (7%) were higher. Twelve of 41 patients (27%) and two of 28 patients (7%) had febrile neutropenia during neoadjuvant and adjuvant treatment, respectively. During neoadjuvant treatment with docetaxel, 13 patients (29%) experienced grade 3/4 non-hematologic toxicities. During adjuvant AC treatment, grade 3/4 non-hematologic toxicities were reported for three patients (11%).
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Studies of single agent pre-operative docetaxel in women with early stage breast cancer have explored dosing every 3 weeks (100 mg/m2) [26] and weekly (36 and 40 mg/m2) [27
, 28
]. The number of cycles has varied among studies and the patient populations have been heterogeneous, often including operable and inoperable disease and a mixture of node-positive and node-negative patients. The overall RRs in these studies have ranged from 67% to 72% and the pCR rates have ranged from 5% to 21%. None have explored standard single agent docetaxel dosing regimens in a group of patients with only stage III disease, and few have reported on long-term survival in this patient population. Therefore, this is the first study to directly assess the safety and efficacy of treating with neoadjuvant, single agent, standard dose docetaxel followed by standard treatment with surgery, adjuvant chemotherapy, radiation and hormonal therapy for the management of stage III breast cancer.
The 5-year survival of 80% for stage III patients enrolled in this study is encouraging, particularly in view of historical data suggesting a 5-year survival of only 50.7% (95% CI 49.9% to 51.5%) for patients with stage III breast cancer diagnosed in the United States in 1995 and 1996 [30]. In the present study, the observed clinical response rate was similar to that described in other studies with docetaxel monotherapy. After four cycles of neoadjuvant docetaxel, an overall response rate of 49% (ITT population) or 56% (evaluable population) was seen in the breast and axilla with a pCR (breast and axilla) of 7% (ITT population) or 10% (evaluable population).
The chemotherapy regimen used in this study had a predictable safety profile and was well tolerated, with neutropenia and febrile neutropenia being the most common hematological toxicities. Grade 3/4 non-hematologic toxicities were not frequent and were similar to prior experience with docetaxel at this dose and with standard AC.
NSABP Protocol B-27 was initiated to evaluate the contribution of docetaxel 100 mg/m2 every 3 weeks when administered as neoadjuvant or adjuvant therapy following four cycles of neoadjuvant AC in women with operable breast cancer (stage III). Compared with neoadjuvant AC alone, patients receiving neoadjuvant AC and docetaxel have shown significant increases in overall clinical response rates (91% versus 86%), cCR rates (64% versus 40%), pCR rates in the breast alone, including patients with residual non-invasive disease (26% versus 14%), and pCR rates of the axillary lymph nodes (58% versus 51%). There was no significant difference in the incidence of breast-conserving surgery (64% versus 62%; P=0.33) [19]. The addition of docetaxel to standard AC improved upon pCR rates in the breast alone in NSABP B-27. The two groups receiving neoadjuvant AC therapy alone had pCR (no invasive or non-invasive tumor) rates of 9.2% and 10.1% compared with 18.9% in the group receiving both neoadjuvant AC and docetaxel [19
]. This incremental improvement in the pCR of about 10% before the addition of docetaxel is similar to pCR rates of 10% seen in our present study. Despite a remarkable increase in pCR with the addition of docetaxel in NSABP B-27, to date this has not translated into a survival benefit compared with the groups not receiving neoadjuvant docetaxel [31
]. However, patients who achieved a pCR had a better survival regardless of treatment.
Similar to NSABP B-27, the GEPAR-DUO study incorporated a treatment arm consisting of AC followed by docetaxel as neoadjuvant treatment in patients with operable breast cancer [18]. The ORR was 85%, and the pCR rate for breast and axilla was 14%. The higher clinical and pathologic response rates in the above mentioned studies might have been due to combination neoadjuvant chemotherapy or an increased number of chemotherapy cycles compared with our study.
Recently, Amat et al. [32] published the results of neoadjuvant docetaxel in operable stage IIIII breast cancer patients. Six cycles of docetaxel were administered at 100 mg/m2 every 3 weeks prior to surgery and RT to 88 patients. The overall clinical response rate of 68% included a CR rate of 19%. Pathologic complete response rates for the breast only were 35.5% with the Sataloff classification and 19.8% with the Chevallier classification. A pCR was defined as total or near total response by the Sataloff classification [33
] and as no tumor in the breast by the Chevallier classification [34
, 35
]. The inclusion of stage II breast cancer patients may have contributed to the high response rates in this study.
The Aberdeen Breast Study Group compared eight cycles of neoadjuvant cyclophosphamide 1000 mg/m2, vincristine 1.5 mg/m2, doxorubicin 50 mg/m2 and prednisone 40 mg (CVAP) with four cycles of neoadjuvant CVAP followed by four cycles of neoadjuvant docetaxel 100 mg/m2 for patients with large (3 cm) or locally advanced breast cancer [29
, 36
]. A significantly greater RR (85% versus 64%) and incidence of breast-conserving surgery (67% versus 48%) were observed for patients receiving CVAP followed by docetaxel compared with patients receiving CVAP alone. The pCR (no invasive tumor cells) rates were 31% versus 15% in the CVAP followed by docetaxel group compared with CVAP alone. At 5 years, OS (93% versus 78%) was significantly greater for the CVAP and docetaxel group compared with the CVAP group, suggesting that the use of sequential, non-cross-resistant chemotherapeutic agents, such as anthracyclines and taxanes, can improve survival [36
].
Various schedules of combinations of docetaxel in the neoadjuvant setting have been tested. Evans et al. [37] compared six cycles of neoadjuvant AC to AT (doxorubicin plus docetaxel) in women with locally advanced, inoperable, inflammatory, or large, operable primary breast cancer. Both the ORR (88% versus 78%) and the pCR rate (8% versus 12%) were comparable for AT and for AC, respectively. A phase II study demonstrated that a combination of docetaxel, doxorubicin and cyclophosphamide (TAC) conferred ORR of 81% and pCR of 8% [38
]. This does not appear to improve upon the historical experience with AC neoadjuvant therapy or with the findings of docetaxel monotherapy reported in the present study. However, preliminary results from the larger, multicenter phase III GEPAR-TRIO study has demonstrated that two cycles of TAC confers an ORR of 74%. Following four additional cycles of TAC, responders to the initial two cycles achieved an ORR of 96% and a pCR of 23% [39
]. Clearly, the duration, schedule and sequence of treatments remain to be optimized.
Citron et al. [40] recently published results from Cancer and Leukemia Group B Protocol 9741 showing differences in DFS at 4 years (75% versus 82%) and OS at 3 years (90% versus 92%) between conventional and bi-weekly (or dose-dense) chemotherapy, respectively, in the adjuvant setting. This dose-dense schedule is also being evaluated in the neoadjuvant setting. For example, the doxorubicin plus docetaxel combination administered every 2 weeks for four cycles has been studied in the GEPAR-DUO study, conferring clinical ORR of 73% (ITT population) and pCR of 7% [18
]. Preliminary results with the use of bi-weekly neoadjuvant docetaxel and vinorelbine appear promising with an ORR of 100%, cCR rate of 59% and pCR rate of 31% for the 43 evaluable patients enrolled in one study [41
].
With the increasing use of taxanes in breast cancer, predicting response and resistance to chemotherapy will be invaluable in clinical decision making. The pre-operative setting provides an opportunity to study the early molecular changes that may occur in response to taxane treatment. Chang et al. [42] performed a cDNA microarray analysis on RNA extracted from core biopsies in 24 breast cancer patients prior to docetaxel treatment. Based on the median residual disease, patients were divided into two roughly equal groups having sensitive or resistant tumors. Differential patterns of expression of 92 genes correlated with docetaxel response (P=0.001). With further validation, cDNA microanalysis could be used as a predictive clinical test of docetaxel sensitivity.
In summary, neoadjuvant docetaxel followed by surgery, adjuvant AC and radiation appears to be an active regimen for stage III breast cancer, with promising long-term survival as seen in the subset of patients who completed study therapy. The aim now lies in finding the best combination, sequence and duration of therapy along with properly predicting and monitoring response. Further studies are needed to optimize treatment regimens so as to increase pathologic response rates and ultimately survival.
![]() |
Acknowledgements |
---|
The following investigators (institution) participated in this study: R. Cohen (University of Virginia Cancer Center, Charlottesville, VA); T.W. Dobbs (Baptist Regional Cancer Center, Knoxville, TN); P. Eisenberg (Marin Oncology Associates, Greenbrae, CA); J. Erban (Tufts New England Medical Center, Boston, MA); W. Gradishar (Northwestern University Medical Center, Chicago, IL); F. A. Greco (Sarah Cannon Cancer Center, Nashville, TN); M. Jahanzeb (Comprehensive Cancer Care, Boca Raton, FL); S. Limentani (Charlotte Medical Center, Charlotte, NC); and K. Loh (Queens Medical Center, Honolulu, HI).
![]() |
Notes |
---|
Received for publication September 30, 2004. Revision received March 4, 2005. Accepted for publication April 15, 2005.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2. Formenti SC, Volm M, Skinner KA et al. Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: A phase I/II trial. J Clin Oncol 2003; 21: 864870.
3. van der Hage JA, van de Velde CJH, Julien J-P et al. Preoperative chemotherapy in primary operable breast cancer: Results from the European Organization for Research and Treatment of Cancer Trial 10902. J Clin Oncol 2001; 19: 42244237.
4. Hortobagyi GN, Singletary SE, Strom EA. Treatment of locally advanced and inflammatory breast cancer. In Harris JR, Lippman ME, Morrow M, Osborne CK (eds): Disease of the Breast. Philadelphia: Lippincott Williams & Wilkins 2000; 645660.
5. von Minckwitz G, Costa SD, Eiermann W et al. Maximized reduction of primary breast tumor size using preoperative chemotherapy with doxorubicin and docetaxel. J Clin Oncol 1999; 17: 19992005.
6. Mamounas EP. Overview of National Surgical Adjuvant Breast Project neoadjuvant chemotherapy studies. Sem Oncol 1998; 25 (Suppl 3): 3135.[ISI][Medline]
7. Wolmark N, Wang J, Mamounas E et al. Preoperative chemotherapy in patients with operable breast cancer: Nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. Presented at The National Institutes of Health Consensus Development Conference: Adjuvant Therapy for Breast Cancer, Bethesda, MD, 13 November 2000.
8. Fisher ER, Wang J, Bryant J et al. Pathobiology of preoperative chemotherapy. Findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP Protocol B-18). Cancer 2002; 95: 681695.[CrossRef][ISI][Medline]
9. Chan S, Friedrichs K, Noel D et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1999; 17: 23412354.
10. Nabholtz J-M, Senn HJ, Bezwoda WR et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol 1999; 17: 14131424.
11. Bonneterre J, Roché H, Monnier A et al. Docetaxel vs. 5-fluorouracil plus vinolrelbine in metastatic breast cancer after anthracycline therapy failure. Br J Cancer 2002; 87: 12101215.[CrossRef][ISI][Medline]
12. Extra J-M, Cognetti F, Chan S et al. Randomized phase III trial (M77001) of trastuzumab (Herceptin®) plus docetaxel versus docetaxel alone as first-line therapy in patients with HER-2 positive metastatic breast cancer. Eur J Cancer 2003; 1 (Suppl 5): S202 (Abstr 672).
13. Nabholtz J-M, Falkson C, Campos D et al. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: Results of a randomized, multicenter, phase III trial. J Clin Oncol 2003; 21: 968975.
14. Mackey JR, Paterson A, Dirix LY et al. Final results of the phase III randomized trial comparing docetaxel (T), doxorubicin (A) and cyclophosphamide (C) to FAC as first-line chemotherapy (CT) for patients (pts) with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2002; 21 (pt 1): 35a (Abstr 137).
15. Miller KD, McCaskill-Stevens W, Sisk J et al. Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: A randomized pilot trial of the Hoosier Oncology Group. J Clin Oncol 1999; 17: 30333037.
16. Tolnai E, Cooper B, Silverman P et al. Dose-dense preoperative chemotherapy with sequential doxorubicin (D) and docetaxel (T) for operable and inoperable stage IIIIIB breast cancer. Breast Cancer Research and Treatment 2000; 64: 69 (Abstr 256).
17. Minton SE, Muro-Cacho C, Diaz N et al. A phase II neoadjuvant trial of sequential doxorubicin and docetaxel for the treatment of stage III breast cancer measuring signal transducers and activators of transcription (STAT) activation as a predictor of response to therapy. Proc Am Soc Clin Oncol 2002; 21 (pt 1): 32a (Abstr 125).
18. Jackisch C, von Minckwitz G, Raab G et al. Primary endpoint analysis of the GEPAR-DUO study-preoperative chemotherapy (PCT) comparing dose-dense versus sequential adriamycin/docetaxel combination in operable breast cancer (T2-3, N0-2, M0). Breast Cancer Res Treat 2002; 76 (Suppl 1): S50 (Abstr 152).
19. Bear HD, Anderson S, Brown A et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: Preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003; 21: 41654174.
20. Limentani SA, Brufsky AM, Erban J et al. Dose-dense neoadjuvant treatment of women with breast cancer utilizing Taxotere and navelbine with growth factor support. Presented at the San Antonio Breast Cancer Symposium, San Antonio, TX, 811 December 2003 (Abstr 251).
21. Malhotra V, Dorr VJ, Lyss AP et al. Neoadjuvant and adjuvant chemotherapy (CT) with doxorubicin and docetaxel (DD) with surgery and radiation in locally advanced breast cancer. Proc Am Soc Clin Oncol 2001; 20 (pt 2): 6b (Abstr 1771).
22. Valero V, Esteva FJ, Sahin AA et al. Phase II trial of neoadjuvant chemotherapy with docetaxel and doxorubicin, surgery, adjuvant CMF, and radiotherapy ± tamoxifen in locally advanced breast cancer. Breast Cancer Res Treat 2000; 64: 69 (Abstr 253).
23. Tubiana-Hulin M, Dieras V, Fumoleau P et al. Phase II trial combining docetaxel (D) and doxorubicin (DOX) in the neoadjuvant setting in patients (PTS) with operable breast carcinoma (BC): Final results. Breast Cancer Res Treat 2000; 64: 69 (Abstr 250).
24. Bouzid K, Vinholes J, Salas F et al. A Phase III trial of Taxotere and doxorubicin (AT) vs 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) in patients with unresectable locally advanced breast cancer: An interim analysis. Eur J Cancer 2001; 37 (Suppl 6): S167 (Abstr 608).
25. von Minckwitz G, Costa SD, Raab G et al. Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: A randomized, controlled, open phase IIb study. J Clin Oncol 2001; 19: 35063515.
26. Chollet PJM, Amat S, Penault-Llorca F et al. Neoadjuvant docetaxel: 4-year survival outcomes and prognostic factors in patients with operable breast cancer. Proc Am Soc Clin Oncol 2003; 22: 48 (Abstr 190).
27. Bines J, Vinholes J, Del Giglio A et al. Neo-adjuvant chemotherapy with weekly docetaxel (taxotere) in poor prognosis locally-advanced breast cancer (LABC). Breast Cancer Res Treat 2002; 76 (Suppl 1): S54 (Abstr 166).
28. Gacia-Estevez L, Cuevas J, Anton A et al. Weekly docetaxel as neoadjuvant treatment in stage II and III breast cancer. Final results of a phase II, multicenter GEICAM study. Eur J Cancer 2002; 38 (Suppl 3): S65 (Abstr 107).
29. Hutcheon AW, Heys SD, Miller ID et al. Improvements in survival in patients receiving primary chemotherapy with docetaxel for breast cancer: A randomised controlled trial. Breast Cancer Res Treat 2001; 69: 298 (Abstr 506).
30. National Cancer Data Base. Commission on Cancer, American College of Surgeons Survival Reports, v 2.0, 11 March 2004; http://www.web.facs.org/ncdbbmr/sas6/surv/GRAPHS/OY96S37XaT00000B.html.
31. Bear HD, Anderson S, Smith RE et al. A randomized trial comparing preoperative (preop) doxorubicin/cyclophosphamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative (postop) T in paients (pts) with operable carcinoma of the breast: results of NSABP B-27. Breast Cancer Res Treat 2004; 88: (Abstr 26).
32. Amat S, Bougnoux P, Penault-Llorca F et al. Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate. Br J Cancer 2003; 88: 13391345.[CrossRef][ISI][Medline]
33. Sataloff DM, Mason BA, Prestipino AJ et al. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg 1995; 180: 297306.[ISI][Medline]
34. Chevallier B, Fumoleau P, Kerbrat P et al. Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the Clinical Screening Cooperative Group of the European Organization for Research and Treatment of Cancer. J Clin Oncol 1995; 13 (2): 314322.
35. Chevallier B, Roche H, Olivier JP et al. Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in a high histologic response rate. Am J Clin Oncol 1993; 16: 223228.[ISI][Medline]
36. Hutcheon AW, Heys SD, Sarkar TK et al. Docetaxel primary chemotherapy in breast cancer: a five year update of the Aberdeen trial. Breast Cancer Res Treat 2003; 82 (Supp 1): S9 (Abstr 11).
37. Evans T, Gould A, Foster E et al. Phase III randomised trial of adriamycin (A) and docetaxel (D) versus A and cyclophosphamide (C) as primary medical therapy (PMT) in women with breast cancer: An ACCOG study. Proc Am Soc Clin Oncol 2002; 21: 35a (Abstr 136).
38. O'Regan R, Malik U, Sparano J et al. Final results of a phase II study of neoadjuvant docetaxel, doxorubicin and cyclophosphamide (TAC) in stage III breast cancer. Proc Am Soc Clin Oncol 2003; 22: 41 (Abstr 163).
39. von Minckwitz G, Raab G, Blohmer JU et al. In vivo chemosensitivity-adapted neoadjuvant chemotherapy (docetaxeldoxorubiincyclophosphamide followed by vinorelbinecapecitabine salvage therapy) in patients with primary breast cancer: results of the GEPAR-TRIO randomized pilot study. Breast Cancer Res Treat 2003; 82 (Suppl 1): S54 (Abstr 236).
40. Citron ML, Berry DA, Cirrincione C et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003; 21: 14311439.
41. Limentani SA, Brufsky AM, Erban J et al. Dose dense neoadjuvant treatment of women with breast cancer utilizing docetaxel and vinorelbine with growth factor support. Proc Am Soc Clin Oncol 2003; 22: 33 (Abstr 131).
42. Chang JC, Wooten EC, Tsimelzon A et al. Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. The Lancet 2003; 362: 362369.[CrossRef][ISI][Medline]
|