-
Gordon F Schwartz,
Harry Bartelink,
Harold J Burstein,
Blake Cady,
Luigi Cataliotti,
Ian S Fentiman,
Roland Holland,
Kevin S Hughes,
Shahla Masood,
Beryl McCormick,
Juan A Palazzo,
Peter I Pressman,
Jorge Reis-Filho,
Lajos Pusztai,
Emiel J T Rutgers, Andrew D Seidman,
Lawrence J Solin,
Joseph A Sparano
[show abstract]
[hide abstract]
ABSTRACT: A consensus conference was held in order to provide guidelines for the use of adjuvant therapy in patients with Stage I carcinoma of the breast, using traditional information, such as tumor size, microscopic character, Nottingham index, patient age and co-morbidities, but also incorporating steroid hormone and Her-2-neu data as well as other immunohistochemical markers. The role of the genetic analysis of breast cancer and proprietary gene prognostic signatures was discussed, along with the molecular profiling of breast cancers into several groups that may predict prognosis. These molecular data are not currently sufficiently mature to make them part of decision making algorithms of recommendations for the treatment of individual patients.
The Breast Journal 07/2012; 18(4):303-11. · 1.64 Impact Factor
-
Patrick G Morris,
Conleth G Murphy,
Divya Mallam,
Melissa Accordino,
Sujata Patil,
Jane Howard,
Antonio Omuro,
Kathryn Beal, Andrew D Seidman,
Clifford A Hudis,
Monica N Fornier
[show abstract]
[hide abstract]
ABSTRACT: Patients with breast cancer, which lacks ER, PR, and HER2; "triple negative" (TNBC), are at increased risk of brain metastases (BMs). However, the impact of modern therapy on the risk of BMs and outcomes remains largely unknown. In this retrospective, single-institution study we assessed the incidence of BMs, the therapeutic options, and overall survival, in a recent cohort of patients with TNBC. Women diagnosed with early stage TNBC from January 1, 1998 to December 31, 2007 were identified through institutional databases. Electronic medical records were reviewed to assess patterns of recurrence, treatment, and survival. In total, 1,323 patients, median age 53 years (range 20-91), were identified. There were 298 patients (23%) who developed metastatic disease, of whom, 99 (33%) developed BMs, representing 7.5% of the entire cohort. Following BM diagnosis, treatment consisted of: radiotherapy 87 (88%) patients, resection 26 (26%) patients, and systemic chemotherapy 70 (71%) patients, with a median of 1.0 (range 0-8) chemotherapy regimens. The actuarial median survival from diagnosis of BMs is 5 months (95% CI 4-7 months). This single-institution, retrospective study confirms that the prognosis for patients with BMs from TNBC remains poor. This group of patients urgently needs improved therapies.
The Breast Journal 05/2012; 18(4):345-50. · 1.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pregnancy-associated breast cancer (PABC) may be defined as breast cancer diagnosed during pregnancy or within 1 year of giving birth. Conflicting data exist regarding the impact of pregnancy on clinical features and prognosis of breast cancer.
A single-institution retrospective chart review was performed of 99 patients identified with PABC between 1992 and 2007. Non-PABC controls were matched 2:1 to PABC cases by year of diagnosis and age. The differences in clinical features were compared between cases and controls using chi-square tests. Univariate and multivariate analyses were performed to assess the effect of PABC on survival.
Of the 99 PABC cases, breast cancer was diagnosed during pregnancy in 36 patients, and after delivery in 63. PABC cases were more likely than controls to be negative for estrogen receptor (59% vs 31%, P < .0001) and negative for progesterone receptor (72% vs 40%, P < .0001). Cases were also more likely to have advanced T class (P = .0271) and N class (P = .0104) and higher grade tumors (P = .0115). With a median follow-up of 6.3 years for cases and 4.7 years for controls, overall survival did not differ between cases and controls (P = .0787). On multivariate analysis, the independent prognostic factors for overall survival were estrogen receptor status (P = .0031) and N class (P = .0003). The diagnosis of PABC was not an independent prognostic factor (P = .1317).
PABC is associated with more adverse tumor features than non-PABC matched for age and year of diagnosis. After correcting for pathologic features, the diagnosis of PABC is not in itself an adverse prognostic factor for survival.
Cancer 11/2011; 118(13):3254-9. · 4.77 Impact Factor
-
Andrew D Seidman
Journal of Clinical Oncology 04/2011; 29(16):2129-30. · 18.37 Impact Factor
-
Heather L McArthur,
Hope Rugo,
Benjamin Nulsen,
Laura Hawks,
Jill Grothusen,
Michelle Melisko,
Mark Moasser,
Matthew Paulson,
Tiffany Traina,
Sujata Patil, [......],
Nancy Sklarin,
Mark Robson,
Mary Ellen Moynahan,
Steven Sugarman,
Jane E Sealey,
John H Laragh,
Carmen Merali,
Larry Norton,
Clifford A Hudis,
Maura N Dickler
[show abstract]
[hide abstract]
ABSTRACT: Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (ddAC) → nanoparticle albumin-bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer.
Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC → nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted.
The median age was 48 years (range, 27-75 years), and baseline LVEF was 68% (53%-82%). After 39 months' median follow-up (5-45 months): median LVEF was 68% (53%-80%) at 2 months (n = 78), 64% (51%-77%) at 6 months (n = 66), 63% (48%-77%) at 9 months (n = 61), and 66% (42%-76%) at 18 months (n = 54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted congestive heart failure (CHF) or HTN, respectively.
Bevacizumab with ddAC → nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials.
Clinical Cancer Research 02/2011; 17(10):3398-407. · 7.74 Impact Factor
-
Pamela Drullinsky,
Steven M Sugarman,
Monica N Fornier,
Gabriella D'Andrea,
Teresa Gilewski,
Diana Lake,
Tiffany Traina,
Carolyn Wasserheit-Lieblich,
Nancy Sklarin,
Deena Atieh-Graham,
Nancy Mills,
Tiffany Troso-Sandoval, Andrew D Seidman,
Jeffrey Yuan,
Hamangi Patel,
Sujata Patil,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule.
Thirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simon's 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%.
The median age was 52-years-old (range, 38-78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals.
Dose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support.
Clinical Breast Cancer 12/2010; 10(6):440-4. · 2.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Knowledge of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) status is necessary for determining the optimal treatment of breast cancer patients. At the same time, the discordance between marker profiles (ER/PR and HER2) of primary and metastatic breast cancer is well documented. Whether discordant cases are secondary to "clonal selection" in the face of targeted anti-estrogen or anti-HER2 therapy or whether they are a laboratory artifact is still debated; both scenarios are likely. This article outlines current modalities for ER, PR, and HER2 testing in primary breast carcinoma and its metastases and reviews prospective and retrospective studies that have addressed these issues, as well as recent advances in the field.
Current Oncology Reports 10/2010; 13(1):17-25. · 2.55 Impact Factor
-
Andrew D Seidman
Clinical advances in hematology & oncology: H&O 09/2010; 8(9):595-7.
-
Alison K Conlin, Andrew D Seidman,
Ariadne Bach,
Diana Lake,
Maura Dickler,
Gabriella D'Andrea,
Tiffany Traina,
Michael Danso,
Adam M Brufsky,
Mansoor Saleh,
Alicia Clawson,
Clifford A Hudis
[show abstract]
[hide abstract]
ABSTRACT: This multicenter phase II trial evaluated the efficacy and safety of weekly nanoparticle albumin-bound paclitaxel with carboplatin and weekly trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer (MBC).
We treated 32 patients who had measurable MBC that was HER2-positive defined by an immunohistochemical staining score of 3+ or gene amplification by fluorescence in situ hybridization, required for those with an IHC of 2+. Patients were treated with albumin-bound paclitaxel 100 mg/m2 and carboplatin at area under the curve (AUC) = 2 on days 1, 8, and 15 of a 28-day cycle. Trastuzumab was administered at 2 mg/kg weekly after a loading dose of 4 mg/kg. Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6-8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis. Patients were treated with 6 cycles and allowed to continue with all 3 drugs or trastuzumab alone if free of progression and unacceptable toxicity after 6 cycles.
The overall response rate (ORR) was 62.5% (95% CI, 45.7%-79.3%) with 3 confirmed complete responders (CRs; 9%) and 17 confirmed partial responses (PRs; 53%). An additional 6 patients (19%) had stable disease (SD) for greater than 16 weeks for a clinical benefit rate (ORR + SD > 16 weeks) of 81%. As of April 16, 2009, 20 patients (63%) had progressed with a median progression-free survival (PFS) of 16.6 months (95% CI, 7.5-26.5 months). Antitumor activity was similar for patients treated with weekly carboplatin and every-4-week carboplatin (ORR, 65% vs. 67%, respectively). Hematologic toxicities were the only grade 4 toxicities noted and were infrequent with grade 4 neutropenia in 3 patients (9%) and 1 febrile neutropenia. Grade 2/3 peripheral neuropathy was uncommon (13%/3%).
Weekly albumin-bound paclitaxel with carboplatin and trastuzumab is highly active in HER2-overexpressing MBC. In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions. The regimen was very well tolerated with few grade 3 and 4 nonhematologic toxicities experienced, and severe hematologic toxicity and peripheral neuropathy were infrequent.
Clinical Breast Cancer 08/2010; 10(4):281-7. · 2.38 Impact Factor
-
Tiffany A Traina,
Hope S Rugo,
James F Caravelli,
Sujata Patil,
Benjamin Yeh,
Michele E Melisko,
John W Park,
Stephanie Geneus,
Matthew Paulson,
Jill Grothusen, Andrew D Seidman,
Monica Fornier,
Diana Lake,
Chau Dang,
Mark Robson,
Maria Theodoulou,
Carlos D Flombaum,
Larry Norton,
Clifford A Hudis,
Maura N Dickler
[show abstract]
[hide abstract]
ABSTRACT: Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC).
Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease.
Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%. Median PFS was 17.1 months.
Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).
Journal of Clinical Oncology 10/2009; 28(4):628-33. · 18.37 Impact Factor
-
Maura N Dickler,
Hope S Rugo,
Carey A Eberle,
Edi Brogi,
James F Caravelli,
Katherine S Panageas,
Jeff Boyd,
Benjamin Yeh,
Diana E Lake,
Chau T Dang,
Teresa A Gilewski,
Jacqueline F Bromberg, Andrew D Seidman,
Gabriella M D'Andrea,
Mark M Moasser,
Michele Melisko,
John W Park,
Janet Dancey,
Larry Norton,
Clifford A Hudis
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway.
Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of > or = 26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis.
One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy.
The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy.
Clinical Cancer Research 01/2009; 14(23):7878-83. · 7.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: As reflected in its varied clinical behavior, appearances under the light microscope, and differential patterns of gene expression, metastatic breast cancer (MBC) is a heterogeneous disease. Systemic treatment decisions are guided by specific tumor characteristics and individual patient factors. For patients with hormone receptor (HR)-negative MBC and for those whose HR-positive disease has become refractory to hormonal therapies, cytotoxic chemotherapy has been the mainstay of systemic treatment. For hormone-insensitive, HER2-positive MBCs, the addition of trastuzumab to chemotherapy has resulted in improved outcomes. Hormone-insensitive MBC lacking HER2 overexpression includes the subset of patients with estrogen receptor/ progesterone receptor/HER2-negative (so-called triple-negative) disease, which represents a significant minority of all breast cancers. Therapeutic options for such patients are limited by the lack of specific targeted approaches, and this heterogeneous group will be considered collectively as well as separately in this overview of existing and emerging treatment strategies. Conventional cytotoxic chemotherapy, alone or in combination, has been the standard first-line treatment for patients with MBC not amenable to antiestrogen or trastuzumab therapy. The recent evaluation of new targeted therapies in combination with cytotoxic agents has created a new type of combination regimen. Agents targeting angiogenesis, the epidermal growth factor receptor, and various signal transduction pathways have been combined with chemotherapy and possess biologic activity in MBC. As these combinations are being investigated, parallel correlative studies aimed at enriching the population who will benefit most are under way.
Clinical Breast Cancer 06/2008; 8(3):215-23. · 2.38 Impact Factor
-
Andrew D Seidman,
Donald Berry,
Constance Cirrincione,
Lyndsay Harris,
Hyman Muss,
P Kelly Marcom,
Grandella Gipson,
Harold Burstein,
Diana Lake,
Charles L Shapiro,
Peter Ungaro,
Larry Norton,
Eric Winer,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: Phase II trials suggested that weekly paclitaxel might be more effective and less toxic than every-3-weeks administration for metastatic breast cancer (MBC). Cancer and Leukemia Group B (CALGB) protocol 9840 was initiated to address this question. Subsequently trastuzumab was demonstrated to improve outcomes of paclitaxel therapy for human epidermal growth factor receptor-2 (HER-2)-positive patients, and was therefore incorporated. Because inhibition of HER-family signaling had potential efficacy even without HER-2 overexpression, we randomly assigned for trastuzumab in this population.
Patients were randomly assigned to paclitaxel 175 mg/m(2) every 3 weeks or 80 mg/m(2) weekly. After the first 171 patients, all HER-2-positive patients received trastuzumab; HER-2 nonoverexpressors were randomly assigned for trastuzumab, in addition to paclitaxel schedule. A total of 577 patients were treated on 9840. An additional 158 patients were included in analyses, for combined sample of 735. The primary end point was response rate (RR); secondary end points were time to progression (TTP), overall survival, and toxicity. Primary comparisons were between weekly versus every-3-weeks paclitaxel, and trastuzumab versus no trastuzumab in HER-2 nonoverexpressors.
In the combined sample, weekly paclitaxel was superior to every-3-weeks administration: RR (42% v 29%, unadjusted odds ratio [OR] = 1.75; P = .0004), TTP (median, 9 v 5 months; adjusted HR = 1.43; P < .0001), and survival (median, 24 v 12 months; adjusted HR = 1.28; P = .0092). For HER-2 nonoverexpressors, trastuzumab did not improve efficacy. Grade 3 neuropathy was more common with weekly dosing (24% v 12%; P = .0003).
Weekly paclitaxel is more effective than every-3-weeks administration for MBC. Trastuzumab did not improve efficacy for HER-2 nonoverexpressors. Neurotoxicity is a treatment-limiting toxicity for weekly paclitaxel.
Journal of Clinical Oncology 05/2008; 26(10):1642-9. · 18.37 Impact Factor
-
Gary Deng,
Andrew Vickers,
Simon Yeung,
Gabriella M D'Andrea,
Han Xiao,
Alexandra S Heerdt,
Steven Sugarman,
Tiffany Troso-Sandoval, Andrew D Seidman,
Clifford A Hudis,
Barrie Cassileth
[show abstract]
[hide abstract]
ABSTRACT: To determine the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer.
Seventy-two women with breast cancer experiencing three or more hot flashes per day were randomly assigned to receive either true or sham acupuncture. Interventions were given twice weekly for 4 consecutive weeks. Hot flash frequency was evaluated at baseline, at 6 weeks, and at 6 months after initiation of treatment. Patients initially randomly assigned to the sham group were crossed over to true acupuncture starting at week 7.
The mean number of hot flashes per day was reduced from 8.7 (standard deviation [SD], 3.9) to 6.2 (SD, 4.2) in the true acupuncture group and from 10.0 (SD, 6.1) to 7.6 (SD, 5.7) in the sham group. True acupuncture was associated with 0.8 fewer hot flashes per day than sham at 6 weeks, but the difference did not reach statistical significance (95% CI, -0.7 to 2.4; P = .3). When participants in the sham acupuncture group were crossed over to true acupuncture, a further reduction in the frequency of hot flashes was seen. This reduction in hot flash frequency persisted for up to 6 months after the completion of treatment.
Hot flash frequency in breast cancer patients was reduced following acupuncture. However, when compared with sham acupuncture, the reduction by the acupuncture regimen as provided in the current study did not reach statistical significance. We cannot exclude the possibility that a longer and more intense acupuncture intervention could produce a larger reduction of these symptoms.
Journal of Clinical Oncology 01/2008; 25(35):5584-90. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The development of superior treatment strategies directed against metastatic breast cancer remains a major challenge. Because
this condition is historically treatable but not curable, the primary goal of clinical management is often to create an optimal
equilibrium between maximizing response, minimizing toxicity, improving survival, and optimizing symptom palliation. The search
for new drugs that might provide these characteristics, together with an expanding understanding of the molecular basis of
cancer, has prompted the development and investigation of “biologic” agents, which offer high tumor selectivity together with
a favorable therapeutic ratio.
10/2007: pages 175-195;
-
[show abstract]
[hide abstract]
ABSTRACT: Metastatic breast cancer is a heterogeneous disease, and treatment decisions depend on several individualized patient and tumor characteristics. Although combination therapy often shows improved response rates in metastatic breast cancer, few studies have shown superiority in overall survival. The choice of combination versus sequential single-agent treatment, therefore, must consider many factors, with no one strategy right for all patients. This article reviews several important clinical trials that address this issue, and argues for single-agent sequential therapy for most patients with metastatic breast cancer.
Journal of the National Comprehensive Cancer Network: JNCCN 10/2007; 5(8):668-72. · 4.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Breast cancer is the most common neoplasia among women in the world. For the last few years there has been an increasing interest in the development of agents against molecular targets considered to be involved in the process of malignant transformation or tumor progression. Experimental data indicate that various intracellular signaling pathways may be activated or overexpressed in patients who have breast cancer. Targeted therapies against these pathways have recently become one of the most active and promising areas of development in oncology.
Hematology/Oncology Clinics of North America 05/2007; 21(2):321-40. · 2.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The decision to use adjuvant chemotherapy in patients with early stage breast cancer involves the consideration of many factors that traditionally rely heavily on tumor size and lymph node involvement and a limited set of biologic characteristics such as estrogen receptor and HER2 expression. Overtreatment with cytotoxic chemotherapy is a significant concern among patients and physicians. Using the currently accepted guidelines it has been estimated that a large percentage of patients receiving chemotherapy for low-risk breast cancers may be overtreated. Gene expression profiling is a new technology being developed to help improve risk stratification of patients and to predict outcomes. The Oncotype DXtrade mark assay is one example of a gene expression profile validated in women with lymph node-negative, estrogen receptor-expressing breast cancer. This assay and others aim to help improve risk classification and recurrence prediction and, therefore, optimize selection of patients for adjuvant chemotherapy.
Molecular diagnosis & therapy 02/2007; 11(6):355-60. · 1.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Over the past decade the taxanes have proved to be fundamental in the treatment of breast cancer. Initially found to have efficacy in metastatic breast cancer, the taxanes are now vital components in the treatment of early-stage disease, in which their addition to adjuvant treatment of early breast cancer has been shown to improve overall survival. In addition, the taxanes have demonstrated a role in first-line therapy for metastatic disease, with some of the highest efficacy of any class of chemotherapy. Targeted therapies in combination with the taxanes have further improved survival for both early and metastatic disease. New formulations of taxanes may both improve antitumor activity and reduce toxicity.
Current Oncology Reports 02/2007; 9(1):22-30. · 2.55 Impact Factor
-
Monica N Fornier, Andrew D Seidman,
Diana Lake,
Gabriella D'Andrea,
Jacqueline Bromberg,
Mark Robson,
Catherine Van Poznak,
Katherine S Panageas,
Marietta Atienza,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: Because Cancer and Leukemia Group B 9741 trial showed a benefit for every 14-day administration of chemotherapy compared with every 21-day treatment, we hypothesized that even greater dose density would be more effective. We conducted a pilot trial to assess the feasibility of dose-dense chemotherapy consisting of a standard regime at 10- to 11-day intervals in the adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling logistics.
Thirty-nine women with early-stage breast carcinoma were accrued from April 2004 to October 2004. Median age was 47 years (range, 26-67 years). Patients received therapy with 100 mg/m(2) epirubicin and 600 mg/m(2) cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175 mg/m(2) paclitaxel q 10 to 11 days for four cycles, all with filgrastim support (300 microg s.c. daily) from day 2 to 24 h before the next treatment.
Thirty-five (90%) patients completed all planned therapy. The median intertreatment interval was 10 days (range, 8-28 days). Cycles (80.7%) were delivered at no more than 10- to 11-day intervals. There were five dose reductions of 25% for grade 3 nonhematologic toxicity in five patients. Six (16%) patients developed febrile neutropenia defined as temperature >38 degrees C with absolute neutrophil count <1,000/microL. All febrile neutropenia was during therapy with EC. Other grade 3 toxicities included bone pain, hand and foot syndrome, neuropathy, mucositis, nausea, and vomiting.
Therapy with EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day intervals is feasible. The approximately 30% reduction in intertreatment interval compared with every 14-day treatment could increase the efficacy of adjuvant chemotherapy.
Clinical Cancer Research 02/2007; 13(1):223-7. · 7.74 Impact Factor
