Papers by Lee Schwartzberg
Journal of Thoracic Oncology, 2009
Introduction: The current standard of care for good performance status patients with locally adva... more Introduction: The current standard of care for good performance status patients with locally advanced non-small cell lung carcinoma is concurrent chemoradiation, although a clearly superior regimen has not been identified. Docetaxel has been shown to possess good single-agent activity against non-small cell lung cancer (NSCLC) and radiosensitizing properties, both alone and synergistically with carboplatin. We undertook this phase II study to determine the safety and efficacy of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxel-carboplatin consolidation for the treatment of locally advanced NSCLC. Methods: Sixty-seven patients having previously untreated stage IIIA or IIIB unresectable NSCLC were enrolled, with 61 patients evaluated for endpoints. Docetaxel 20 mg/m 2 IV infusion over 30 minutes followed by carboplatin area under the curve ϭ 2 over 30 minutes was administered weekly during concurrent thoracic radiotherapy. After 3 week rest, consolidation docetaxel 75 mg/m 2 IV infusion over 60 minutes and carboplatin area under the curve ϭ 6 over 30 minutes was administered every 3 weeks for two cycles. Concurrent thoracic radiation consisted of 45 Gy (1.8 Gy fractions 5 d/wk for first 5 weeks) followed by 18 Gy boost (2.0 Gy fractions 5 d/wk for 2 weeks) for a total dose of 63 Gy. Results: One and 2 years overall survival rates were 45 and 20%, respectively. Progression free survival at 1 year was 27%. Median survival time was 12 months. Median time to progression was 8 months. The primary hematologic toxicity was leukopenia. The primary nonhematologic toxicity was esophagitis. Conclusion: The administered regimen of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxelcarboplatin consolidation has acceptable toxicity profile. However, the overall survivals at 1 and 2 years are somewhat disappointing.
Journal of Thoracic Oncology, 2013
Introduction: There is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for in... more Introduction: There is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non-small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed. Methods: In this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non-small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64-68 Gy over days 1-45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate.
Journal of Clinical Oncology, 2006
Purpose To evaluate the effect of bexarotene on survival in patients with relapsed non–small-cell... more Purpose To evaluate the effect of bexarotene on survival in patients with relapsed non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIB NSCLC with pleural effusion or stage IV NSCLC, who had Eastern Cooperative Oncology Group performance status 0 to 2, and were previously treated with ≥ two different regimens that must have included a platinum and a taxane, received oral bexarotene 400 mg/m2/d plus concomitant levothyroxine and a lipid-lowering agent. Primary efficacy end point was survival. Results For the 146 assessable patients treated with bexarotene, median age was 66 years (range, 34 to 87 years), 51% were men, and the median number of prior regimens was three (range, one to seven). The overall median survival was 5 months (95% CI, 4 to 7 months) and the 1-year survival was 23% (95% CI, 16% to 31%). Survival was significantly longer in patients with bexarotene-induced hypertriglyceridemia and/or skin rash. In 26 patients who had both adverse effect...
Supportive Care in Cancer, 2017
Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of can... more Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT 3) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK 1 RAs when combined with 5-HT 3 RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a twodrug (ondansetron-dexamethasone) combination in nausea control after cisplatin-or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). R e c e n t l y, d e x a m e t h a s o n e a n d d e x a m e t h a s o n emetoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK 1 RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK 1 RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment. Keywords NK 1 receptor antagonist. Chemotherapy-induced nausea (CIN). Chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines * Snežana M. Bošnjak
The Oncologist, 2019
Background NEPA, a combination antiemetic of a neurokinin-1 (NK1) receptor antagonist (RA) (netup... more Background NEPA, a combination antiemetic of a neurokinin-1 (NK1) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5-HT3RA, palonosetron] offers 5-day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion-site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK1RAs, particularly fosaprepitant in patients receiving anthracycline-cyclophosphamide (AC)-based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting. Materials and Methods This phase IIIb, multinational, randomized, double-blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30-minute infusion of IV NEPA or single oral NEPA capsule o...
Supportive Care in Cancer, 2018
Clinical advances in hematology & oncology : H&O, 2016
Health and quality of life outcomes, Jan 14, 2017
Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line i... more Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line include platinum-based doublet therapy with or without bevacizumab. This study examined efficacy outcomes and patient reported outcomes (PROs) in a community oncology patient sample. Advanced nonsquamous NSCLC patients from 34 U.S. community oncology practices treated in first line with bevacizumab regimens (A platinum doublet; gemcitabine doublet; pemetrexed with platinum) or non-bevacizumab regimens (B platinum doublet; gemcitabine doublet; C pemetrexed with platinum) were recruited for this prospective study. Patient characteristics and clinical outcomes were accessed from routine care records. Three validated and widely used PRO measures of health related quality of life (HRQOL) and symptom burden were collected prospectively at each visit and up to one-year follow-up. Effectiveness outcomes were progression free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier and Co...
Journal of the National Comprehensive Cancer Network : JNCCN, 2017
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all as... more The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.
Breast cancer research and treatment, Jan 13, 2017
Conventional chemotherapy has limited activity in patients with breast cancer and brain metastase... more Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conduct...
Supportive Care in Cancer, 2016
Purpose Addition of rolapitant to standard antiemetic therapy improved protection against chemoth... more Purpose Addition of rolapitant to standard antiemetic therapy improved protection against chemotherapy-induced nausea and vomiting (CINV) in phase 3 trials of patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Here, we assessed the impact of CINV on the daily lives of patients receiving HEC or MEC using the Functional Living Index-Emesis (FLIE). Methods In three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy. Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included FLIE total score, nausea and vomiting domain scores, and the proportion of patients with no impact on daily life (total score >108 [range 18-126]). We performed a prespecified analysis of the MEC/ anthracycline-cyclophosphamide (AC) study and a post hoc analysis of two pooled cisplatin-based HEC studies. Results In the pooled HEC studies, rolapitant significantly improved the FLIE total score (114.5 vs 109.3, p < 0.001), nausea score (55.3 vs 53.5, p < 0.05), and vomiting score (59.2 vs 55.8, p < 0.001) versus control; similar results were observed in the MEC/AC study for FLIE total score (112.7 vs 108.6, p < 0.001), nausea score (54.1 vs 52.3, p < 0.05), and vomiting score (58.6 vs 56.3, p < 0.001). A higher proportion of patients reported no impact on daily life with rolapitant than with control in the MEC/AC study (73.2 vs 67.4, p = 0.027). Conclusions Compared with control, rolapitant improved quality of life in patients receiving HEC or MEC.
European journal of cancer (Oxford, England : 1990), Jan 3, 2016
Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed c... more Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly ...
BioMed Research International, 2015
Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have... more Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV) related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1receptor antagonist (RA), netupitant, and the pharmacologically and clinically distinct 5-HT3RA, palonosetron. This convenien...
Clinical advances in hematology & oncology : H&O, 2011
Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and troubling side effe... more Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and troubling side effects of treatment, and the side effect cancer patients tend to fear most. An improved understanding of the pathophysiology underlying CINV, together with a clear definition of the risk for nausea and vomiting associated with specific chemotherapeutic agents, has for allowed the development of specific and effective antiemetic regimens. Antiemesis is most effective when used prophylactically, a principle shared among CINV management guidelines. Several antiemetic drug classes are available; among the most effective of these are serotonin (5HT₃) receptor antagonists, neurokinin 1 (NK₁) receptor antagonists, and steroids (primarily dexamethasone), although others are commonly used as well. When choosing an appropriate antiemetic regimen, clinicians should consider patient-specific factors such as sex and prior history of CINV, as well as treatment-specific factors such as the emetogenic pot...
Clinical advances in hematology & oncology : H&O, 2011
One of the most dreaded side effects of anticancer treatment, chemotherapy-induced nausea and vom... more One of the most dreaded side effects of anticancer treatment, chemotherapy-induced nausea and vomiting (CINV) plays a significant role in cancer patients' morbidity and quality of life. The management of CINV has been refined over the past several decades, and CINV can now be addressed with targeted prophylactic medications aimed at inhibiting the molecular pathways involved in emesis, including serotonin receptor antagonists and neurokinin-1 receptor antagonists. Advances in the understanding of the physiology of CINV, coupled with the introduction of several agents that inhibit activation of these receptors, are reflected in current CINV guidelines. These guidelines, which are largely similar, provide recommendations based on expert review of available clinical trial data. Despite the availability of effective prophylaxis, many patients still suffer from CINV. To minimize these side effects, clinicians should ensure widespread adoption and implementation of at least 1 CINV gui...
Clinical breast cancer, 2014
In this phase II study, we explored efficacy and toxicity of combined endocrine and low-dose metr... more In this phase II study, we explored efficacy and toxicity of combined endocrine and low-dose metronomic chemotherapy therapy consisting of fulvestrant and capecitabine in estrogen and/or progesterone receptor-positive, HER2-negative MBC. Patients with ≤ 1 previous hormonal treatment in the metastatic setting received an injection fulvestrant loading dose 500 mg on day 1, 250 mg on days 15 and 29 followed by 250 mg every 28 days along with continuous oral capecitabine in divided doses. The total fixed daily dose of capecitabine was either 1500 mg or 2000 mg, depending on the patient's weight (< 80 kg vs. ≥ 80 kg). Primary end points were PFS and TTP. Toxicity was assessed by continuous evaluations of treatment-emergent adverse events (AEs) and changes from baseline in laboratory values. Forty-one women, with a mean age of 64.5 years, were enrolled. Patients completed a median of 11 monthly treatment cycles. Median PFS was 14.98 months (95% confidence interval [CI], 7.26-upper ...
Value in Health, 2011
Two systematic reviews of literature have been conducted. One focused on the efficacy, identifyin... more Two systematic reviews of literature have been conducted. One focused on the efficacy, identifying health technology agencies reports, meta-analysis, systematic reviews, and randomized controlled trials (RCTs). The safety systematic review included the previous designs plus observational studies. In the latter review, studies in subsequent lines of treatment were considered. Searches were done in MED-LINE, EMBASE, CRD, and the Cochrane Library until the 8th of June. The quality assessment of the studies was done with the SIGN and CASPe tools. Two authors independently selected the studies, assessed the quality, and performed the data extraction, with disagreements resolved by a third reviewer until consensus was obtained. RESULTS: In the efficacy systematic review, three RCTs were included. The chemotherapy in one of these trials was FOLFIRI, in another trial FOLFOX-4, and in the other one was oxaliplatin and fluoropyrimidine chemotherapy. In the safety systematic review, five RCTs (3 studies in first-line, one study in second-line and another with cetuximab in monotherapy in subsequent lines), and an observational study were considered. Cetuximab in combination with FOLFIRI improved overall survival (OS), resection rate, progression free survival (PFS) and overall tumour response rate (RR). Whereas, an increase in terms of OS was not observed with cetuximab in combination with oxaliplatin based regimen, and different results were obtained in PFS. The only benefit observed with the later regimen was in the RR. In terms of safety, cetuximab increased grade 3 or 4 skin toxicity. CONCLUSIONS: The benefit of the addition of cetuximab to standard therapy for previously untreated mCRC, KRAS wild-type patients differs depending on the chemotherapy associated, with an improvement in all the outcomes when FOLFIRI is used.
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Papers by Lee Schwartzberg