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ABSTRACT: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has demonstrated clinical benefit in metastatic breast cancer (MBC) in a randomized phase III trial versus paclitaxel (CA012; N = 454) and in a randomized phase II trial versus docetaxel (CA024; N = 300). This retrospective analysis examines whether patients with poor prognostic factors demonstrate similar outcomes to the intent-to-treat (ITT) populations in these trials. This retrospective analysis evaluated the efficacy and safety of previously untreated patients with MBC with the following poor prognostic factors: visceral dominant metastases and short disease-free interval (DFI; ≤2 years). In CA012 (n = 186 first-line patients), nab-paclitaxel demonstrated a significantly higher overall response rate (ORR) versus paclitaxel in patients with visceral dominant metastases (42 vs. 23 %; P = 0.022), whereas the higher ORR for nab-paclitaxel in patients with a short DFI (43 vs. 33 %; P = NS) was not statistically significant. In CA024, a significantly higher ORR for nab-paclitaxel 150 mg/m(2) versus docetaxel was observed in patients with visceral dominant metastases (76 vs. 37 %; P < 0.001). No significant differences in ORR were observed in patients with a short DFI. Although progression-free survival (PFS) and overall survival showed trends similar to ORR, statistical significance was only achieved for comparisons of PFS in patients with visceral dominant metastases in CA024 (13.1 months for nab-paclitaxel 150 mg/m(2) vs. 7.8 months for docetaxel [P = 0.019] and 7.5 months for nab-paclitaxel 100 mg/m(2) [P = 0.010]). Safety results were similar to previous reports of the ITT populations. nab-Paclitaxel demonstrated similar efficacy in patients with poor prognostic factors as in the ITT populations of these two trials. In each trial, ORR was significantly higher for nab-paclitaxel versus the comparator taxane among patients with visceral dominant metastases.
Breast Cancer Research and Treatment 04/2013; · 4.43 Impact Factor
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CancerSpectrum Knowledge Environment 01/2013; 105(2):149-50. · 14.07 Impact Factor
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ABSTRACT: At least 14 stratifiers exist to assess recurrence risk, chemotherapy response, and overall survival (OS) in women with early-stage breast cancer (ESBC). These stratifiers have not been compared using a recently developed rigorous framework. We performed a systematic review of the literature on clinical validity/utility, change in clinical practice, and economic implications of ESBC stratifiers.
A systematic literature search was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews, and bibliographies of relevant studies. Data were extracted by two investigators and graded using a previously published framework. The Level-of-Evidence determination for each study was summarized, and the studies that provide evidence on change in clinical practice and economic implications are reported.
Fifty-six articles published original evidence addressing the 21-gene recurrence score (n = 31), 70-gene signature (n = 14), Adjuvant! Online (n = 12), 5-antibody immunohistochemistry panel (n = 3), 5-gene expression index (n = 1), and 14-gene signature (n = 1). The 21-gene recurrence score satisfied Level I evidence (the highest level of evidence among five levels) for estimating distant recurrence risk (DRR), OS, and response to adjuvant chemotherapy, and Level II for estimating local recurrence risk. The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS. Adjuvant! Online satisfied Level II evidence for estimating DRR, OS, and chemotherapy response. The 5-gene expression index satisfied Level III evidence for predicting DRR. The 14-gene signature satisfied Level III evidence for predicting DRR and OS. Ten studies reported changes in clinical practice patterns; seven studies reported economic implications.
The available evidence on the ability of stratifiers to predict risks of recurrence and response to chemotherapy in ESBC is growing. Level-of-Evidence determinations using the newer framework provide a solid scientific foundation for clinical recommendations.
CancerSpectrum Knowledge Environment 07/2012; 104(14):1068-79. · 14.07 Impact Factor
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
Stephen B Edge,
William B Farrar,
Andres Forero,
Sharon Hermes Giordano,
Lori J Goldstein, William J Gradishar, [......],
Elizabeth C Reed,
Mary Lou Smith,
Hatem Soliman,
George Somlo,
Richard L Theriault,
John H Ward,
Antonio C Wolff,
Richard Zellars,
Rashmi Kumar,
Dorothy A Shead
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ABSTRACT: These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option.
Journal of the National Comprehensive Cancer Network: JNCCN 07/2012; 10(7):821-9. · 4.41 Impact Factor
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ABSTRACT: A randomized phase II study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel. Final survival analyses and updated safety results are reported.
Three hundred two patients with no previous chemotherapy for MBC were randomized to receive nab-paclitaxel 300 mg/m(2) q3w, nab-paclitaxel 100 mg/m(2) or 150 mg/m(2) the first 3 of 4 weeks (qw 3/4), or docetaxel 100 mg/m(2) q3w. The trial was powered for analyses of antitumor activity and safety.
Treatment with nab-paclitaxel 150 mg/m(2) qw 3/4 resulted in a median overall survival (OS) of 33.8 months compared with 22.2, 27.7, and 26.6 months for nab-paclitaxel 100 mg/m(2) qw 3/4, nab-paclitaxel 300 mg/m(2) q3w, and docetaxel, respectively (overall P = .047). Patients receiving 150 mg/m(2)nab-paclitaxel had prolonged median OS compared with those in the 100 mg/m(2)nab-paclitaxel arm (hazard ratio, 0.575; P = .008). A trend toward a longer OS was noted in the 150 mg/m(2)nab-paclitaxel arm versus docetaxel arm (hazard ratio, 0.688). Grade 3 or 4 fatigue, neutropenia, and febrile neutropenia were less frequent in all nab-paclitaxel arms compared with docetaxel.
Consistent with previously published efficacy results, these data suggest that 150 mg/m(2) qw 3/4 may represent the most clinically efficacious nab-paclitaxel dosing regimen for patients with no previous chemotherapy for MBC. A phase III trial confirming these results would be necessary and prudent before widespread adoption of the 150 mg/m(2) dose in clinical practice.
Clinical Breast Cancer 06/2012; 12(5):313-21. · 2.38 Impact Factor
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ABSTRACT: Capecitabine produces an objective response rate of up to 25% in anthracycline-treated, taxane-resistant metastatic breast cancer (MBC). The farnesyltransferase inhibitor tipifarnib inhibits Ras signaling and has clinical activity when used alone in MBC. The objective of this study was to determine the efficacy and safety of tipifarnib-capecitabine combination in MBC patients who were previously treated with an anthracycline and progressed on taxane therapy. Eligible patients received oral capecitabine 1,000 mg/m2 twice daily plus oral tipifarnib 300 mg twice daily on days 1-14 every 21 days. The primary endpoint was ORR. The trial was powered to detect an improvement in response rate from 25 to 40%. Among 63 eligible, partial response occurred in six patients (9.5%; 90% CI 4.2-17.9%), median progression-free survival was 2.6 months (95% CI 2.1-4.4), and median overall survival was 11.4 months (95% CI 7.7-14.0). Dose modifications were required for 43 patients (68%) for either tipifarnib and/or capecitabine. Grades 3 and 4 toxicities were seen in 30 patients (44%; 90% CI 44.4-67.0%) and 11 patients (16%; 90% CI 10.8-29.0%), respectively. The most common grade 3 toxicities included neutropenia, nausea, and vomiting; and the most common grade 4 toxicity was neutropenia (8 out of 11 cases). The tipifarnib-capecitabine combination is not more effective than capecitabine alone in MBC patients who were previously treated with an anthracycline and taxane therapy.
Breast Cancer Research and Treatment 05/2012; 134(1):345-52. · 4.43 Impact Factor
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William J Gradishar
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ABSTRACT: Treatment of metastatic breast cancer (MBC) remains one of the major challenges in cancer care. Chemotherapeutic agents currently approved for the treatment of invasive disease may exhibit initial efficacy; however, the development of resistance to therapy and concerns over tolerability are common and generally limit treatment options available to physicians and patients. Novel chemotherapeutic agents are, therefore, necessary to increase survival, delay disease progression, and improve tolerability. Eribulin mesylate (E7389) is a novel microtubule dynamics inhibitor with a unique mechanism of action that has shown antitumor efficacy and a manageable tolerability profile in clinical trials. Importantly, eribulin is the only single agent to date that has been shown to prolong overall survival in patients with heavily pretreated MBC. This review will discuss eribulin, with focus on the potential it has to address the specific treatment needs of patients with MBC who are refractory to conventional chemotherapies.
Current Oncology Reports 02/2011; 13(1):11-6. · 2.55 Impact Factor
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
W Bradford Carter,
Stephen B Edge,
John K Erban,
William B Farrar,
Andres Forero,
Sharon Hermes Giordano, [......],
Ingrid A Mayer,
Beryl McCormick,
Lori J Pierce,
Elizabeth C Reed,
Jasgit Sachdev,
Mary Lou Smith,
George Somlo,
John H Ward,
Antonio C Wolff,
Richard Zellars
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ABSTRACT: Overview These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer are the work of the members of the NCCN Breast Cancer Panel. Categories of evidence and consensus were assessed and are noted in the algorithms and text. Although not explicitly stated at every decision point of the NCCN Guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer. The full breast cancer guidelines are not printed in this issue of JNCCN, but can be accessed online at www.NCCN.org. The American Cancer Society estimated that 209,060 new cases of invasive breast cancer were diagnosed and 40,230 people died of breast cancer in the United States in 2010.(1) In addition, approximately 54,010 women were diagnosed with carcinoma in situ of the breast during the same year. Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The incidence of breast cancer has increased steadily in the United States over the past few decades, but breast cancer mortality seems to be declining,(1,2) suggesting a benefit from early detection and more effective treatment. The cause of most breast cancer cases is unknown. However, numerous risk factors for the disease have been established, including female gender, increasing patient age, family history of breast cancer at a young age, early menarche, late menopause, older age at first live birth, prolonged hormone replacement therapy, previous exposure to therapeutic chest...
Journal of the National Comprehensive Cancer Network: JNCCN 02/2011; 9(2):136-222. · 4.41 Impact Factor
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Therese B Bevers,
Deborah K Armstrong,
Banu Arun,
Robert W Carlson,
Kenneth H Cowan,
Mary B Daly,
Irvin Fleming,
Judy E Garber,
Mary Gemignani, William J Gradishar, [......],
Deborah J Macdonald,
Martin C Mahoney,
Sofia D Merajver,
Ingrid Meszoely,
Lisa Newman,
Elizabeth Pritchard,
Victoria Seewaldt,
Rena V Sellin,
Charles L Shapiro,
John H Ward
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ABSTRACT: Breast cancer is the most commonly diagnosed cancer in American women with 209,060 and 54,010 estimated cases of invasive breast cancer and female carcinoma in situ, respectively, in 2010. Approximately 39,840 women will die of breast cancer in the United States in 2010.(1) Risk factors for the development of breast cancer can be grouped into categories, including familial/genetic factors (family history, known or suspected BRCA1/2, TP53, PTEN, or other gene mutation associated with breast cancer risk); factors related to demographics (e.g., age, ethnicity/race); reproductive history (age at menarche, parity, age at first live birth, age at menopause); environmental factors (prior thoracic irradiation before age 30 years [e.g., to treat Hodgkin disease], hormone replacement therapy [HRT], alcohol consumption); and other factors (e.g., number of breast biopsies, atypical hyperplasia or lobular carcinoma in situ [LCIS], breast density, body mass index). Estimating breast cancer risk for the individual woman is difficult, and most breast cancers are not attributable to risk factors other than female gender and increased age. The development of effective strategies for the reduction of breast cancer incidence has also been difficult because few of the existing risk factors are modifiable and some of the potentially modifiable risk factors have social implications extending beyond concerns for breast cancer (e.g., age at first live birth). Nevertheless, effective breast cancer risk reduction agents/strategies, such as tamoxifen, raloxifene, and risk reduction surgery, have been identified. However, women and their physicians who are considering interventions to reduce risk for breast cancer must balance the demonstrated...
Journal of the National Comprehensive Cancer Network: JNCCN 11/2010; 8(10):1112-46. · 4.41 Impact Factor
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
W Bradford Carter,
Stephen B Edge,
John K Erban,
William B Farrar,
Andres Forero,
Sharon Hermes Giordano, [......],
Ingrid A Mayer,
Beryl McCormick,
Lori J Pierce,
Elizabeth C Reed,
Mary Lou Smith,
George Somlo,
Neal S Topham,
John H Ward,
Eric P Winer,
Antonio C Wolff
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ABSTRACT: Overview The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer: Noninvasive and Special Situations presented here are the work of the NCCN Breast Cancer panel members. Categories of evidence and consensus were assessed and are noted in the algorithms and text. Although not explicitly stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer. These NCCN Guidelines focus on noninvasive breast cancer and special situations, such as Paget's disease, phyllodes tumor, breast cancer during pregnancy, and axillary breast cancer. Another NCCN guideline addresses invasive breast cancer (see NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Breast Cancer: Invasive and Inflammatory; to view the complete and most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org). The American Cancer Society estimates that 194,280 new cases of invasive breast cancer were diagnosed and 40,610 died of the disease in the United States in 2009.(1) In addition, approximately 62,280 women were diagnosed with carcinoma in situ of the breast during the same year. Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The incidence of breast cancer has increased steadily in the United States over the past few decades, but breast cancer mortality seems to be declining,(1,2) suggesting a benefit from early detection and more effective treatment. The origin of most breast cancer...
Journal of the National Comprehensive Cancer Network: JNCCN 11/2010; 8(10):1182-207. · 4.41 Impact Factor
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William J Gradishar
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ABSTRACT: Aromatase inhibitors (AIs) have largely replaced tamoxifen as adjuvant hormonal therapy for postmenopausal women with early breast cancer. While tamoxifen is effective in reducing breast cancer recurrence and mortality, recent data indicate two peaks of early, mostly distant metastatic recurrences in patients receiving tamoxifen, and AIs have proven more effective in reducing recurrence. As distant recurrence has been associated with poorer survival and death, reduction in this type of early recurrence event may lead to improved survival over the long term. Recent data from major clinical trials are beginning to bear out this contention.
Cancer Investigation 05/2010; 120(5):433-42. · 1.85 Impact Factor
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ABSTRACT: The epothilone B analogue, ixabepilone, binds to b-tubulin, is effective for taxane-refractory metastatic breast cancer (MBC), and may be given every 3 weeks or weekly. We evaluated the efficacy of weekly ixabepilone (I) plus trastuzumab (T) and carboplatin (C) as first line therapy in HER2 + MBC. Patients with HER2+ (3+ by IHC or FISH amplified) MBC received I (15 mg/m2 IV) and C (area under the curve, AUC = 2 IV) on days 1, 8, and 15 of a 28-day cycle for a maximum of 6 cycles, plus weekly T (4 mg/kg loading dose then 2 mg/kg IV) during chemotherapy then every 3 weeks (6 mg/kg IV) until disease progression. The primary objective was to determine whether the combination was associated with a response rate (RR) of at least 75%. Fifty-nine patients were treated, and 39 had HER2 overexpression confirmed in a central lab (cHER2+). For all treated patients, objective response occurred in 26 patients (44%; 95% CI 31-58%), median time to progression was 8.2 months (95% CI 6.3-9.9), and median overall survival was 34.7 months (95% CI 25.7 to [not reached]). Results were comparable for cHer2? cancers. Grade 3-4 adverse events included neutropenia (49%), thrombocytopenia (14%), fatigue (12%), nausea (7%), diarrhea (7%), and neuropathy (7%). One patient died from treatment complications during cycle 1. Weekly ixabepilone and carboplatin plus trastuzumab have an acceptable toxicity profile, but are not likely to be associated with an RR of 75% in HER2+ MBC. Efficacy appears comparable to paclitaxel, carboplatin, and trastuzumab.
Breast Cancer Research and Treatment 12/2009; 119(3):663-71. · 4.43 Impact Factor
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ABSTRACT: Capecitabine (Xeloda®) is an orally administered chemotherapeutic agent, widely used for metastatic breast cancer treatment. Preclinical and clinical studies demonstrate selective enzymatic conversion of capecitabine into 5-fluorouracil, a potent cytotoxic agent within malignant tumors. Capecitabine is the only cytotoxic agent without cumulative toxicity and it exhibits synergistic activity when used in combination with a wide range of other cytotoxic and biologic agents. Capecitabine monotherapy results in an objective response rate of 15-37% in patients with metastatic breast cancer in the adjuvant setting. A combination regimen of capecitabine with docetaxel (Taxotere®) improves overall survival in metastatic breast cancer compared with docetaxel monotherapy. Treatment-refractory, heavily pretreated and elderly patients have experienced positive outcomes with capecitabine, demonstrating its utility in diverse populations. Multiple trials suggest that initiating capecitabine treatment with lower daily doses may improve its safety and tolerability profile without compromising efficacy.
Expert Review of Obstetrics & Gynecology 06/2009; 4(4):367-376.
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ABSTRACT: In patients with metastatic breast cancer (MBC), nab-paclitaxel produced significantly higher antitumor activity compared with patients who received solvent-based paclitaxel. This phase II study examined the antitumor activity and safety of weekly and every 3 week (q3w) nab-paclitaxel compared with docetaxel as first-line treatment in patients with MBC.
In this randomized, multicenter study, patients (N = 302) with previously untreated MBC received nab-paclitaxel 300 mg/m(2) q3w, 100 mg/m(2) weekly, or 150 mg/m(2) weekly or docetaxel 100 mg/m(2) q3w.
nab-Paclitaxel 150 mg/m(2) weekly demonstrated significantly longer progression-free survival (PFS) than docetaxel by both independent radiologist assessment (12.9 v 7.5 months, respectively; P = .0065) and investigator assessment (14.6 v 7.8 months, respectively; P = .012). On the basis of independent radiologist review, both 150 mg/m(2) (49%) and 100 mg/m(2) (45%) weekly of nab-paclitaxel demonstrated a higher overall response rate (ORR) than docetaxel (35%), but this did not reach statistical significance. This trend was supported by statistically significant investigator ORR for both weekly nab-paclitaxel doses versus docetaxel. nab-Paclitaxel q3w versus docetaxel was not different for PFS or ORR. On the basis of both the independent radiologist and investigator review, disease control rate was significantly higher for patients receiving either dose of weekly nab-paclitaxel compared with docetaxel. Grade 3 or 4 fatigue, neutropenia, and febrile neutropenia were less frequent in all nab-paclitaxel arms. The frequency and grade of peripheral neuropathy were similar in all arms.
This randomized study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel, with a statistically and clinically significant prolongation of PFS (> 5 months) in patients receiving nab-paclitaxel 150 mg/m(2) weekly compared with docetaxel 100 mg/m(2) q3w.
Journal of Clinical Oncology 06/2009; 27(22):3611-9. · 18.37 Impact Factor
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ABSTRACT: Recently, recommendations for the use of the Oncotype DX assay in estrogen receptor-positive node-negative breast cancer patients were incorporated into guidelines from both the American Society of Clinical Oncology and the National Comprehensive Cancer Network. The Oncotype DX assay is a diagnostic test which measures changes in a set of 21 genes in order to predict the likelihood of disease recurrence and also to predict which patients are most likely to respond to chemotherapy. Oncotype DX has been available commercially since January 2004 and has been used for more than 85,000 patients. Drs. William J. Gradishar, Nora M. Hansen, and Barbara Susnik answered questions regarding the incorporation of the Oncotype DX breast cancer assay into routine clinical practice. This expert dialog offers an update and clinical insights into when, how, and why clinicians might incorporate the Oncotype DX assay into the management of their breast cancer patients. Also, the latest research into the benefit of the Oncotype DX assay in node-positive patients is discussed. Finally, sample case studies offer clinically relevant examples of the practical application of the Oncotype DX assay.
Clinical advances in hematology & oncology: H&O 05/2009; 7(4):1-7.
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
W Bradford Carter,
Stephen B Edge,
John K Erban,
William B Farrar,
Lori J Goldstein, William J Gradishar, [......],
Lisle M Nabell,
Lori J Pierce,
Elizabeth C Reed,
Mary Lou Smith,
George Somlo,
Richard L Theriault,
Neal S Topham,
John H Ward,
Eric P Winer,
Antonio C Wolff
Journal of the National Comprehensive Cancer Network: JNCCN 03/2009; 7(2):122-92. · 4.41 Impact Factor
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Martee L Hensley,
Karen L Hagerty,
Tarun Kewalramani,
Daniel M Green,
Neal J Meropol,
Todd H Wasserman,
Gary I Cohen,
Bahman Emami, William J Gradishar,
R Brian Mitchell,
J Tate Thigpen,
Andy Trotti,
Daniel von Hoff,
Lynn M Schuchter
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ABSTRACT: To update a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer.
An update committee reviewed literature published since the last guideline update in 2002.
Thirty-nine reports met the inclusion criteria: palifermin and dexrazoxane, three reports (two studies) each; amifostine, 33 reports (31 studies); and mesna, no published randomized trials identified since 2002.
Dexrazoxane is not recommended for routine use in breast cancer (BC) in adjuvant setting, or metastatic setting with initial doxorubicin-based chemotherapy. Consider use with metastatic BC and other malignancies, for patients who have received more than 300 mg/m(2) doxorubicin who may benefit from continued doxorubicin-containing therapy. Cardiac monitoring should continue in patients receiving doxorubicin. Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity, reduction of grade 3 to 4 neutropenia (alternative strategies are reasonable), and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer. It is not recommended for protection against thrombocytopenia, prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy, prevention of radiation therapy-associated mucositis in head and neck cancer, or prevention of esophagitis during concurrent chemoradiotherapy for non-small-cell lung cancer. Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation (SCT) for hematologic malignancies with total-body irradiation (TBI) conditioning regimens, and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens. Data are insufficient to recommend use in the non-SCT setting.
Journal of Clinical Oncology 12/2008; 27(1):127-45. · 18.37 Impact Factor
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ABSTRACT: Nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) is an albumin-bound 130-nm particle form of paclitaxel that demonstrated higher efficacy and was well tolerated compared with solvent-based paclitaxel (Taxol) and docetaxel (Taxotere) in clinical trials for metastatic breast cancer. Nab-paclitaxel enhances tumor targeting through gp60 and caveolae-mediated endothelial transcytosis and the association with the albumin-binding protein SPARC (secreted protein, acidic and rich in cysteine) in the tumor microenvironment. The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer has been shown to correlate with resistance to paclitaxel. To evaluate the importance of HER2 and SPARC status in determining the relative efficacy of nab-paclitaxel compared with polysorbate-based docetaxel, nude mice bearing six different human tumor xenografts were treated with nab-paclitaxel (MX-1: 15 mg/kg, once a week for 3 weeks; LX-1, MDA-MB-231/HER2+, PC3, and HT29: 50 and 120 mg/kg, every 4 days three times ; MDA-MB-231: 120 and 180 mg/kg, every 4 days three times) and polysorbate-based docetaxel (15 mg/kg). HER2 and SPARC status were analyzed by RT-PCR and immunohistochemical staining. MDA-MB-231 and MX-1 breast and LX-1 lung cancers were HER2 negative and low in SPARC expression. Nab-paclitaxel at submaximum-tolerated dosage was significantly more effective than polysorbate-based docetaxel at its maximum-tolerated dosage in these three HER2-negative tumors. The HER2-positive tumors had variable SPARC expression, with MDA-MB-231/HER2+ <PC3 <HT29. In these HER2-positive tumors, nab-paclitaxel was equal to or better than polysorbate-based docetaxel in tumors with medium to high SPARC levels (PC3 and HT29), but not in MDA-MB-231/HER2+ tumors with low SPARC expression. These results demonstrated that the relative efficacy of nab-paclitaxel was significantly higher compared with polysorbate-based docetaxel in HER2-negative tumors (three of three) and in HER2-positive tumors with high levels of SPARC. HER2 and SPARC expression may be useful biomarkers in determining antitumor effectiveness for taxanes.
Anti-Cancer Drugs 10/2008; 19(9):899-909. · 2.41 Impact Factor
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New England Journal of Medicine 10/2008; 359(13):1382-91. · 53.30 Impact Factor
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Robert W Carlson,
Susan Moench,
Arti Hurria,
Lodovico Balducci,
Harold J Burstein,
Lori J Goldstein, William J Gradishar,
Kevin S Hughes,
Mohammad Jahanzeb,
Stuart M Lichtman,
Lawrence B Marks,
Joan S McClure,
Beryl McCormick,
Lisle M Nabell,
Lori J Pierce,
Mary Lou Smith,
Neal S Topham,
Tiffany A Traina,
John H Ward,
Eric P Winer
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ABSTRACT: Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the "older" breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies.
Journal of the National Comprehensive Cancer Network: JNCCN 01/2008; 6 Suppl 4:S1-25; quiz S26-7. · 4.41 Impact Factor
