Maura N Dickler

Publications (18)126.36 Total impact

• Article: Nonimmediate Hypersensitivity Reaction After Trastuzumab Infusion: A Suspected Drug-Virus Interaction.

  Denisa E Ferastraoaru, Maura N Dickler, Sima Patel, Erica A Fischer, Melissa P Pulitzer, Patricia L Myskowski, Elina Jerschow
  Journal of Clinical Oncology 06/2013; · 18.37 Impact Factor
• Source

  Available from: Clifford Hudis

  Article: A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer.

  Hope S Rugo, A Jo Chien, Sandra X Franco, Alison T Stopeck, Alexa Glencer, Soumi Lahiri, Michael C Arbushites, Janet Scott, John W Park, Clifford Hudis, Ben Nulsen, Maura N Dickler
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  ABSTRACT: Preclinical data have demonstrated that the combination of antihuman epidermal growth factor receptor-2 (anti-HER2) and antivascular endothelial growth factor (anti-VEGF)--targeted agents has antitumor activity; these data indicate certain patients with HER2-overexpressing breast cancer may derive clinical benefit from this combination. The purpose of this single-arm phase II study was to determine the efficacy and safety of the dual-targeting combination of lapatinib and bevacizumab. Women with HER2-overexpressing advanced breast cancer received 1,500 mg oral lapatinib daily plus 10 mg/kg IV bevacizumab every 2 weeks. The primary endpoint was progression-free survival (PFS) at week 12; secondary endpoints included overall tumor response rate (ORR), clinical benefit rate (CBR), duration of response, time-to-response, PFS, and safety. Circulating tumor cells (CTC) and circulating endothelial cells (CEC) were measured at baseline and during study treatment as potential response markers. Fifty-two patients with stage IV disease were enrolled. The 12-week investigator-assessed PFS rate was 69.2% (95% confidence interval [CI]: 54.9, 81.3). Median PFS was 24.7 weeks (95% CI: 20.4, 35.1), and the CBR was 30.8% (95% CI: 18.7, 45.1). Of 45 patients with measurable disease, 6 were determined to have a partial response per Response Evaluation Criteria in Solid Tumors (ORR: 13.3%; 95% CI: 5.1, 26.8). The most common adverse events (AEs) included diarrhea, rash, and fatigue; most of these were either grade 1 or 2. Clinical responses were correlated with decreases in CTC and CEC. Lapatinib plus bevacizumab was active in patients with HER2-overexpressing breast cancer. The AE profile of the combination was consistent with the known profiles for these agents.
  Breast Cancer Research and Treatment 12/2011; 134(1):13-20. · 4.43 Impact Factor
• Article: Targeting the insulin-like growth factor pathway in estrogen receptor-positive breast cancer: a bumpy start with an uncertain future.

  Maura N Dickler
  Journal of Clinical Oncology 09/2011; 29(29):3846-8. · 18.37 Impact Factor
• Article: HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab.

  Shanu Modi, Alison Stopeck, Hannah Linden, David Solit, Sarat Chandarlapaty, Neal Rosen, Gabriella D'Andrea, Maura Dickler, Mary E Moynahan, Steven Sugarman, Weining Ma, Sujata Patil, Larry Norton, Alison L Hannah, Clifford Hudis
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  ABSTRACT: HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer. We enrolled patients with metastatic HER2(+) breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m(2) intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 17 months (95% CI: 16-28). This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted.
  Clinical Cancer Research 05/2011; 17(15):5132-9. · 7.74 Impact Factor
• Article: Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib.

  Patrick G Morris, Carol Chen, Richard Steingart, Martin Fleisher, Nancy Lin, Beverly Moy, Steven Come, Steven Sugarman, Alyson Abbruzzi, Robert Lehman, Sujata Patil, Maura Dickler, Heather L McArthur, Eric Winer, Larry Norton, Clifford A Hudis, Chau T Dang
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  ABSTRACT: There are no validated methods of early detection of cardiotoxicity from trastuzumab (T) following anthracycline-based chemotherapy. Currently changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Within a prospective feasibility study of dose-dense (dd) doxorubicin and cyclophosphamide (AC) → weekly paclitaxel (P) with T and lapatinib (L), we included a preplanned analysis of correlative cardiac Troponin I (cTnI) and C-reactive protein (CRP) as early biomarkers of cardiotoxicity. As previously described, patients received ddACx 4 → PTL → TL. LVEF was assessed at months 0, 2, 6, 9, and 18 and cTnI and CRP measured every 2 weeks during chemotherapy then at months 6, 9, and 18. These biomarkers were correlated with changes in LVEF. Ninety-five patients enrolled. Overall, 3 (3%) patients withdrew during AC and 41 (43%) withdrew during PTL → TL, mostly due to diarrhea. Median LVEF was 68% (baseline), 69% (month 2), 65% (month 6), 65% (month 9), and 65% (month 18). The majority (67%) had a detectable cTnI during the study. The proportion of detectable cTnIs increased over time; 4% at baseline, 11% at month 2, and 50% at month 3. The timing of these detectable cTnIs preceded maximum-recorded decline in LVEF. However, overall, maximum cTnI levels did not correlate with LVEF declines. A detectable CRP was seen in 74/95 (78%) but did not correlate with LVEF declines. In patients receiving ddAC → PTL, cTnIs are commonly detected. These elevations may precede changes in LVEF but, as assessed in this trial, do not predict CHF.
  Clinical Cancer Research 03/2011; 17(10):3490-9. · 7.74 Impact Factor
• Article: Bevacizumab in metastatic breast cancer: when may it be used?

  Shari B Goldfarb, Clifford Hudis, Maura N Dickler
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  ABSTRACT: Tumor angiogenesis, which is necessary for breast cancer growth, invasion and metastases, is regulated by pro-angiogenic factors such as vascular endothelial growth factor (VEGF). Bevacizumab is a recombinant humanized monoclonal antibody that targets VEGF. The addition of bevacizumab to chemotherapy has improved progression-free survival in the first- and second-line treatment of patients with advanced-stage breast cancer. In this article we review the clinical trials testing the utility of bevacizumab for the treatment of metastatic disease.
  rapeutic Advances in Medical Oncology, The 03/2011; 3(2):85-93.
• Article: Updates on therapeutic approaches in HER2-positive disease.

  Maura N Dickler
  Clinical advances in hematology & oncology: H&O 02/2010; 8(2):105-7.
• Article: Bevacizumab for advanced breast cancer.

  Shari B Goldfarb, Tiffany A Traina, Maura N Dickler
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  ABSTRACT: Tumor angiogenesis is an important step in breast cancer development, progression, invasion and metastasis. Pro-angiogenic factors such as VEGF regulate angiogenesis and are targets for drug development. Bevacizumab, an anti-VEGF antibody, has demonstrated significant clinical benefit in several solid tumors, including breast cancer. Its use in combination with either paclitaxel or docetaxel has prolonged progression-free survival and increased response rates in the first-line treatment of patients with metastatic breast cancer. This review article discusses the clinical trials establishing the use of bevacizumab for the treatment of advanced breast cancer.
  Women s Health 01/2010; 6(1):17-25.
• Article: Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer.

  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
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  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
• Article: A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer.

  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
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  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
• Article: Aromatase inhibitors and arthralgia: a growing pain?

  Conleth Murphy, Clifford A Hudis, Maura N Dickler
  Oncology (Williston Park, N.Y.) 12/2008; 22(12):1424, 1426. · 1.03 Impact Factor
• Article: Biomarkers in breast cancer.

  Heather L McArthur, Maura N Dickler
  Cancer biology & therapy 02/2008; 7(1):21-2. · 2.64 Impact Factor
• Article: When you look matters: the effect of assessment schedule on progression-free survival.

  Katherine S Panageas, Leah Ben-Porat, Maura N Dickler, Paul B Chapman, Deborah Schrag
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  ABSTRACT: Progression-free survival (PFS) is increasingly used as an endpoint for cancer clinical trials. Disease progression is typically assessed on the basis of radiologic testing at scheduled time points or after a fixed number of treatment cycles. The date of the radiologic evaluation at which progression is first evident is used as a proxy for the true progression time. The true progression time actually lies somewhere within the time interval between two assessments, a situation that results in interval-censored data. An analysis that ignores this interval censoring and uses the detection date as the date of progression unavoidably results in an overestimation of median PFS. This overestimation can erroneously result in a result being described as clinically significant when in fact a longer median PFS may just be a consequence of the length of the surveillance interval. Furthermore, if surveillance intervals are heterogenous within a disease group, comparisons of median PFS across studies may not be meaningful. The decision to use PFS as a primary endpoint should be made carefully when designing clinical trials, and investigators focused on a particular disease should develop consensus standards and strive for consistent surveillance intervals.
  CancerSpectrum Knowledge Environment 04/2007; 99(6):428-32. · 14.07 Impact Factor
• Article: The MORE Trial: Multiple Outcomes for Raloxifene Evaluation

  MAURA N. DICKLER, LARRY NORTON
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  ABSTRACT: Breast cancer is a common disease in the United States and Europe and is therefore a major target for prevention strategies. Estrogen plays a central role in its pathogenesis, and treatment with estrogen deprivation has long been recognized to be an effective therapy. Tamoxifen is the first selective estrogen receptor modulator (SERM) to be widely used for the treatment of breast cancer and has been demonstrated to reduce the risk of breast cancer in high-risk women. Raloxifene is a second-generation SERM that has estrogenic effects on bone and lipid metabolism, and antiestrogenic effects on breast tissue. Unlike tamoxifen, raloxifene displays antiestrogenic effects on the endometrium and may serve as a safer alternative to tamoxifen in the prevention setting. The MORE trial is a multicenter randomized placebo-controlled trial designed to determine whether 3 years of raloxifene reduces the risk of fracture in postmenopausal women with osteoporosis. As a secondary end point of the trial, raloxifene was shown to reduce the risk of both in situ and invasive breast cancer by 65% (RR = 0.35; 95% CI = 0.21-0.58; P < 0.001). The benefits were most significant in women who developed estrogen receptor (ER)-positive cancers, with a relative risk of 0.10 (95% CI = 0.04-0.24). This reduced incidence of breast cancer may be due to an anticarcinogenic effect or to a slowing of growth of occult ER-positive cancer, with a shift to the right in the time-to-cancer curve. A second large-scale prevention trial in breast cancer comparing tamoxifen to raloxifene is presently enrolling cancer-free, but high-risk postmenopausal women (the STAR trial). Future directions include combined estrogen blockade of the breast by the addition of an aromatase inhibitor to a SERM. New trial designs, including those based on biochemical changes at the tissue level, will be required to allow future progress in this field with adequate rapidity.
  Annals of the New York Academy of Sciences 01/2006; 949(1):134 - 142. · 3.15 Impact Factor
• Article: Phase II study of feasibility of dose-dense FEC followed by alternating weekly taxanes in high-risk, four or more node-positive breast cancer.

  Chau T Dang, Gabriella M D'Andrea, Mary E Moynahan, Maura N Dickler, Andrew D Seidman, Monica Fornier, Mark E Robson, Maria Theodoulou, Diana Lake, Violante E Currie, Arti Hurria, Katherine S Panageas, Larry Norton, Clifford A Hudis
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  ABSTRACT: To develop a potentially superior adjuvant chemotherapy regimen, we conducted a pilot study of dose-dense 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by weekly alternating taxanes. The primary objective was to determine the feasibility of the regimen; the secondary objective was to estimate the disease-free and overall survival. Patients with >/=4 node-positive breast cancer were studied. Treatment consisted of FEC at 500/100/500 mg/m(2), respectively, x6 at two-week intervals with granulocyte colony-stimulating factor, followed by weekly paclitaxel (80 mg/m(2)) alternating with docetaxel (35 mg/m(2)) x18. Between November 2001 and January 2003, 44 patients were enrolled. Median age was 46 years (range, 26-63 years), median number of positive nodes was 9 (range, 4-32), and median tumor size was 2.5 cm (range, 0.6-11.0 cm). Because of unexpected toxicities, the study was stopped when 17 (39%) had fully completed all of the planned treatment. Two of 17 (12%) developed grade 4 pericardial/grade 3 bilateral pleural effusions at treatment completion; both required pericardial window. The remaining patients were treated with taxanes using one of several standard dose and schedule combinations. Furthermore, 4 of 44 (9%) developed pneumonitis attributed to the FEC regimen. Hospital admissions were required for 12 of 44 (27%); 3 of 44 (7%) required blood transfusions. There were no treatment related deaths. Median disease-free and overall survival will not be estimatable because of early closure of study. FEC x6 at 2-week intervals followed by 18 weeks of alternating taxanes is not feasible at the doses tested. Other strategies are needed to improve adjuvant systemic chemotherapy.
  Clinical Cancer Research 10/2004; 10(17):5754-61. · 7.74 Impact Factor
• Article: Aromatase inhibitors for hormonal therapy of early-stage breast cancer.

  Tiffany A Traina, Maura N Dickler
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  ABSTRACT: Aromatase inhibitors block estrogen synthesis by inhibiting aromatase, the enzyme responsible for the conversion of adrenal steroids to estrogen. They are approved for the first-line treatment of metastatic breast cancer in hormone receptor-positive women. Three large, well-designed randomized trials have been reported which support the use of aromatase inhibitors in the treatment of early stage breast cancer. This review focuses on data on aromatase inhibitors in the adjuvant setting and looks to the future potential of these drugs in both ductal carcinoma in situ and chemoprevention.
  Current opinion in investigational drugs (London, England: 2000) 07/2004; 5(6):605-10. · 3.31 Impact Factor
• Article: Phase II study of celecoxib and trastuzumab in metastatic breast cancer patients who have progressed after prior trastuzumab-based treatments.

  Chau T Dang, Andrew J Dannenberg, Kotha Subbaramaiah, Maura N Dickler, Mark M Moasser, Andrew D Seidman, Gabriella M D'Andrea, Maria Theodoulou, Katherine S Panageas, Larry Norton, Clifford A Hudis
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  ABSTRACT: Preclinical studies demonstrate a link between overexpression of HER-2/neu and cyclooxygenase-2 (COX-2) activity. To explore the possibility that COX-2 is a therapeutic target, we conducted a phase II study of celecoxib, a selective COX-2 inhibitor, and trastuzumab in patients with HER-2/neu-overexpressing metastatic breast cancer that had progressed while receiving trastuzumab. Eligible patients had bi-dimensionally measurable or evaluable HER-2/neu-overexpressing metastatic breast cancer. HER-2/neu overexpression, defined as 2+ or 3+ by the HercepTest, was required. Patients had to have progressed despite prior trastuzumab-based therapy. Treatment consisted of celecoxib (400 mg twice daily) and trastuzumab. Twelve patients were enrolled (42% status post 1 regimen for metastatic disease 58% status post > 2 prior regimens (range of 2-6). Eleven patients were evaluable. There were no responses. Median duration of treatment was 9 weeks. One patient had stable disease at 3 months but progressed at 6 months. A second patient stopped treatment at 3 months because of unresolved grade 2 rash, felt to be related to celecoxib. Toxicities were generally grade 1 or 2. One patient (8%) experienced grade 3 toxicity (abdominal pain). Celecoxib combined with trastuzumab is well tolerated. However, this combination in patients with HER2/neu-overexpressing, trastuzumab-refractory disease, was not active.
  Clinical Cancer Research 06/2004; 10(12 Pt 1):4062-7. · 7.74 Impact Factor
• Article: Maximizing the potential of bevacizumab in cancer treatment.

  Emily Bergsland, Maura N Dickler
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  ABSTRACT: Promising results have been obtained with bevacizumab (Avestin; Genentech, Inc.; South San Francisco, CA) in clinical trials in patients with a range of solid tumors; however, to maximize the potential of this agent, further research is needed to clarify a number of important issues. These include the optimization of bevacizumab dosage and schedule of administration, the potential value of this agent in combination with other treatment modalities like chemotherapy and radiation, the management of toxicities, and the selection of patients most likely to benefit from treatment. Intriguing results from two recent phase III trials highlight the need for a better understanding of the best ways to incorporate bevacizumab into clinical practice. Ultimately, maximizing the potential value of this agent may require a more thorough understanding of bevacizumab's mechanism of action and the pathways mediating resistance.
  The Oncologist 02/2004; 9 Suppl 1:36-42. · 3.91 Impact Factor