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1.
Cancers (Basel) ; 16(8)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38672538

ABSTRACT

BACKGROUND: This study further evaluated the safety and efficacy of the combination of alisertib and sapanisertib in an expansion cohort of patients, including a subset of patients with refractory pancreatic adenocarcinoma, with further evaluation of the pharmacodynamic characteristics of combination therapy. METHODS: Twenty patients with refractory solid tumors and 11 patients with pancreatic adenocarcinoma were treated at the recommended phase 2 dose of alisertib and sapanisertib. Adverse events and disease response were assessed. Patients in the expansion cohort were treated with a 7-day lead-in of either alisertib or sapanisertib prior to combination therapy, with tumor tissue biopsy and serial functional imaging performed for correlative analysis. RESULTS: Toxicity across treatment groups was overall similar to prior studies. One partial response to treatment was observed in a patient with ER positive breast cancer, and a patient with pancreatic cancer experienced prolonged stable disease. In an additional cohort of pancreatic cancer patients, treatment response was modest. Correlative analysis revealed variability in markers of apoptosis and immune cell infiltrate according to lead-in therapy and response. CONCLUSIONS: Dual targeting of Aurora A kinase and mTOR resulted in marginal clinical benefit in a population of patients with refractory solid tumors, including pancreatic adenocarcinoma, though individual patients experienced significant response to therapy. Correlatives indicate apoptotic response and tumor immune cell infiltrate may affect clinical outcomes.

2.
Rehabil Oncol ; 40(2): 82-88, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35711819

ABSTRACT

BACKGROUND: Cancer-related fatigue (CRF) is one of the most reported and functionally limiting symptoms experienced by individuals living with and beyond cancer. Exercise is effective at reducing CRF, though currently it is not possible to predict the magnitude and time course of improvement for an individual participating in an exercise program. OBJECTIVE: To develop a reference chart of CRF improvement for individuals participating in a 3-month cancer-specific exercise program. METHODS: In this retrospective cohort study, CRF was assessed every two weeks (using the FACIT - Fatigue scale, range: 0 - 52 with lower scores indicating greater fatigue) in 173 individuals participating in a 3-month supervised exercise program (741 observations). No cancer types were excluded and individuals were either undergoing chemotherapy and/or radiation, or within 6 months of completing treatment. The reference chart was developed using Generalized Additive Models for Location Scale and Shape. RESULTS: Each participant had an average of four CRF observations. Lower centiles demonstrated greater improvement than higher centiles (11 points over the duration of the program for the 10th and 4 points for the 90th percentiles). LIMITATIONS: The population is biased to individuals self-selecting or being referred to a clinical exercise program. CONCLUSIONS: This reference chart provides a novel method of monitoring CRF improvement during a cancer-specific exercise program. Setting appropriate expectations and informing exercise prescription adaptation are discussed in the context of representative data from three participants. Future research can investigate improvements in clinical outcomes and the remote monitoring of CRF through the implementation of the reference chart.

3.
Support Care Cancer ; 29(11): 6801-6806, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33993408

ABSTRACT

CONTEXT: Psychological distress is common in patients with cancer, and oncology providers are often tasked with utilizing psychotropic medications to treat such symptoms. OBJECTIVE: This study aims to characterize how oncology providers prescribe psychotropic medications and to assess their comfort level with prescribing these medications. METHODS: A cross-sectional survey was sent to oncology medical doctors, nurse practitioners, and physician assistants who prescribe psychotropic medications to patients with cancer at a large academic medical center in the Mountain West. The survey included questions regarding provider subspecialty, degree, comfort with prescribing psychotropic medications, and factors that informed their prescribing. RESULTS: Oncology providers (n = 65) reported equal proportions of comfort and discomfort with prescribing psychotropic medications. The medication class with the most prescribers was benzodiazepines, with 89.2% (n = 58) of the respondents prescribing those medications. The least prescribed category was mood stabilizers, with 4.6% (n = 3) prescribing this category. Prescribers identified that barriers to their comfort included difficulty connecting patients to follow-up care with mental health professionals and inadequate mental health education for providers. Providers responded that continuing mental health education and increasing patient access to mental health resources would increase their prescribing comfort. CONCLUSION: Providers reported equal parts comfort and discomfort with prescribing psychotropic medications; avenues to increase comfort should involve focused mental health education during formal training and continued education throughout their oncology careers. A clinical pathway for prescribing psychotropic medications with resources to connect patients to long-term mental health care may also increase prescribing comfort.


Subject(s)
Nurse Practitioners , Psychotropic Drugs , Cross-Sectional Studies , Humans , Psychotropic Drugs/therapeutic use , Surveys and Questionnaires
4.
J Natl Compr Canc Netw ; 19(6): 726-732, 2021 03 11.
Article in English | MEDLINE | ID: mdl-33706258

ABSTRACT

BACKGROUND: Cancer care coordination across major academic medical centers and their networks is evolving rapidly, but the spectrum of organizational efforts has not been described. We conducted a mixed-methods survey of leading cancer centers and their networks to document care coordination and identify opportunities to improve geographically dispersed care. METHODS: A mixed-methods survey was sent to 91 cancer centers in the United States and Canada. We analyzed the number and locations of network sites; access to electronic medical records (EMRs); clinical research support and participation at networks; use of patient navigators, care paths, and quality measures; and physician workforce. Responses were collected via Qualtrics software between September 2017 and December 2018. RESULTS: Of the 69 responding cancer centers, 74% were NCI-designated. Eighty-seven percent of respondents were part of a matrix health system, and 13% were freestanding. Fifty-six reported having network sites. Forty-three respondents use navigators for disease-specific populations, and 24 use them for all patients. Thirty-five respondents use ≥1 types of care path. Fifty-seven percent of networks had complete, integrated access to their main center's EMRs. Thirty-nine respondents said the main center provides funding for clinical research at networks, with 22 reporting the main center provides all funding. Thirty-five said the main center provided pharmacy support at the networks, with 15 indicating the main center provides 100% pharmacy support. Certification program participation varied extensively across networks. CONCLUSIONS: The data show academic cancer centers have extensive involvement in network cancer care, often extending into rural communities. Coordinating care through improved clinical trial access and greater use of patient navigation, care paths, coordinated EMRs, and quality measures is likely to improve patient outcomes. Although it is premature to draw firm conclusions, the survey results are appropriate for mapping next steps and data queries.


Subject(s)
Neoplasms , Patient Navigation , Physicians , Certification , Electronic Health Records , Humans , Neoplasms/epidemiology , Neoplasms/therapy , Surveys and Questionnaires , United States
5.
Support Care Cancer ; 29(7): 3425-3428, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33594510

ABSTRACT

PURPOSE: Exercise programs delivered in community- or clinic-based settings improve physical and psychosocial outcomes among cancer survivors; however, adherence is essential to achieve such benefits. This study examined predictors of attendance to an exercise program in a large, diverse sample of cancer survivors. METHODS: Participants (n = 302) were enrolled in BfitBwell, an exercise program for adults diagnosed with cancer, and currently receiving or within 6 months of completing chemotherapy or radiation therapy. Participants were offered two supervised aerobic and resistance exercise sessions per week for 3 months. Predictors of attendance included demographics, cancer-related information, quality of life (QOL), fatigue, physical fitness, activity level, and importance of making various changes (e.g., improving fitness). Univariate linear regression first explored associations between predictor variables and adherence, and any important variables (p < .10) were included in a multivariate linear regression model. RESULTS: Participants were M = 54.9 ± 13.9 years old, mostly female (67.3%), white (83.6%), and most commonly diagnosed with breast cancer (34.8%). Average attendance was 16.2 ± 6.6 exercise sessions. Six-minute walk test distance, QOL, and fatigue were associated with exercise session attendance (p < .05). The multivariable model revealed that higher QOL predicted higher attendance (ß = .351, p = .005), and working full- or part-time significantly predicted lower attendance (ß =- .221, p =.021). CONCLUSIONS: Higher pre-program QOL and not working full- or part-time predicted higher exercise program attendance. Existing and future exercise programs for cancer survivors should consider ways to adapt program delivery to provide support to survivors who start with low QOL, and accommodate those who may face barriers to attending due to work schedule/conflict.


Subject(s)
Cancer Survivors/psychology , Exercise Therapy/methods , Quality of Life/psychology , Female , Humans , Male , Middle Aged
6.
Integr Cancer Ther ; 19: 1534735420975852, 2020.
Article in English | MEDLINE | ID: mdl-33243013

ABSTRACT

INTRODUCTION: Sleep disturbance is the second leading negative side effect reported by cancer survivors, and evidence exists to suggest that exercise may improve sleep for cancer survivors. This study examined changes in sleep following a 3-month, clinic-based exercise program among a diverse group of cancer survivors. METHODS: Single group, pre-post study design. Participants were enrolled in a supervised exercise program which consisted of moderate intensity aerobic and resistance training, twice per week for 3-months. To be eligible, individuals had to be diagnosed with cancer, and undergoing, or within 6-months of completing chemo and/or radiation therapy. Sleep was assessed at pre-and post-program using 3 self-report questions as part of a standard wellness assessment conducted at the program's facility. Changes in categorical outcomes were evaluated using McNemar and Wilcoxon Signed-Rank Tests. RESULTS: Participants (N = 94) were mostly female (68.1%, N = 64), mean age = 54.26 ± 14.26 (20-78), and diagnosed with more than 8 different cancer types. Half (N = 48, 51.1%) of participants improved on 1 or more of the questions assessing sleep. At post-program, 39% of participants reported that they did not awaken feeling rested versus 48% at pre-program (P = .08). At post-program, 47% reported awakening ≥1 time per night versus 46% at pre-program (P = .97), and 17% reported poor or very poor sleep quality at post-program versus 24% at pre-program (P = .16). There were no differences in demographic, cancer-related, psychosocial, and physical fitness variables between participants who improved on any of the questions assessing sleep versus those who did not. CONCLUSIONS: A clinically implemented exercise program may help some cancer survivors improve sleep, however more studies utilizing validated, objective measures of sleep are needed to confirm effectiveness.


Subject(s)
Cancer Survivors , Neoplasms , Exercise Therapy , Female , Humans , Male , Middle Aged , Quality of Life , Sleep , Survivors
7.
Clin Cancer Res ; 24(14): 3334-3347, 2018 07 15.
Article in English | MEDLINE | ID: mdl-29636358

ABSTRACT

Purpose: Despite initial benefit from tyrosine kinase inhibitors (TKIs), patients with advanced non-small cell lung cancer (NSCLC) harboring ALK (ALK+) and ROS1 (ROS1+) gene fusions ultimately progress. Here, we report on the potential resistance mechanisms in a series of patients with ALK+ and ROS1+ NSCLC progressing on different types and/or lines of ROS1/ALK-targeted therapy.Experimental Design: We used a combination of next-generation sequencing (NGS), multiplex mutation assay, direct DNA sequencing, RT-PCR, and FISH to identify fusion variants/partners and copy-number gain (CNG), kinase domain mutations (KDM), and copy-number variations (CNVs) in other cancer-related genes. We performed testing on 12 ROS1+ and 43 ALK+ patients.Results: One of 12 ROS1+ (8%) and 15 of 43 (35%) ALK + patients harbored KDM. In the ROS1+ cohort, we identified KIT and ß-catenin mutations and HER2-mediated bypass signaling as non-ROS1-dominant resistance mechanisms. In the ALK+ cohort, we identified a novel NRG1 gene fusion, a RET fusion, 2 EGFR, and 3 KRAS mutations, as well as mutations in IDH1, RIT1, NOTCH, and NF1 In addition, we identified CNV in multiple proto-oncogenes genes including PDGFRA, KIT, KDR, GNAS, K/HRAS, RET, NTRK1, MAP2K1, and others.Conclusions: We identified a putative TKI resistance mechanism in six of 12 (50%) ROS1 + patients and 37 of 43 (86%) ALK+ patients. Our data suggest that a focus on KDMs will miss most resistance mechanisms; broader gene testing strategies and functional validation is warranted to devise new therapeutic strategies for drug resistance. Clin Cancer Res; 24(14); 3334-47. ©2018 AACR.


Subject(s)
Anaplastic Lymphoma Kinase/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Drug Resistance, Neoplasm/genetics , Lung Neoplasms/genetics , Oncogene Proteins, Fusion , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Adult , Aged , Anaplastic Lymphoma Kinase/chemistry , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Computational Biology/methods , DNA Copy Number Variations , Female , High-Throughput Nucleotide Sequencing , Humans , In Situ Hybridization, Fluorescence , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Male , Middle Aged , Models, Molecular , Molecular Targeted Therapy , Mutation , Oncogene Proteins, Fusion/chemistry , Oncogene Proteins, Fusion/genetics , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/chemistry , Proto-Oncogene Proteins/chemistry , Structure-Activity Relationship , Young Adult
8.
J Thorac Oncol ; 13(1): 134-138, 2018 01.
Article in English | MEDLINE | ID: mdl-28843358

ABSTRACT

INTRODUCTION: The role of serum tumor markers in the modern management of advanced NSCLC remains poorly described. METHODS: A single-center retrospective analysis of available carcinoembryonic antigen, CA125, CA19.9, and CA27.29 levels at baseline and during treatment of stage IV lung adenocarcinoma by oncogenic driver was conducted. RESULTS: A total of 142 patients were analyzed (60 with anaplastic lymphoma kinase gene [ALK] rearrangement, 50 with EGFR mutation, four with ROS1 rearrangement, and 29 with KRAS mutation). Of these, 82% had at least one marker (95% if all four markers were measured), with CA27.29 being the most commonly increased and CA19.9 the rarest. Only CA27.29 differed significantly by oncogene (it was less common in KRAS) (p = 0.016). The median times to nadir during tyrosine kinase inhibitor (TKI) therapy in EGFR and ALK cases were 16.4 and 20 weeks, respectively. Of the 41 patients with EGFR mutation or ALK or ROS1 rearrangement, 24 (59%) demonstrated an initial increase within the first 4 weeks of TKI therapy, 58% of whom then had their levels fall below baseline. An increase in marker level of 10% or more from nadir occurred in 53% of systemic and 22% of central nervous system-only progression. CONCLUSIONS: Serum tumor markers are frequently increased in lung adenocarcinoma regardless of driver oncogene. Changes within the first 4 weeks of therapy may be misleading. Progression is associated with marker increases, especially in sites other than the central nervous system.


Subject(s)
Adenocarcinoma/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers/blood , Gene Rearrangement , Lung Neoplasms/blood , Mutation , Neoplasm Recurrence, Local/blood , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Biomarkers/metabolism , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Retrospective Studies , Survival Rate
9.
J Thorac Oncol ; 13(5): 715-720, 2018 05.
Article in English | MEDLINE | ID: mdl-29269007

ABSTRACT

INTRODUCTION: Patients with brain metastases (BMs) arising from EGFR-mutated and anaplastic lymphoma kinase gene (ALK)-rearranged NSCLC have a favorable prognosis compared with patients with non-oncogene-addicted NSCLC, emphasizing the importance of minimizing toxicities such as the cognitive sequelae of whole brain radiation therapy (WBRT). Although radiosurgery without WBRT is the preferred strategy for one to three BMs, this paradigm remains controversial for patients with multiple BMs. METHODS: We reviewed the cases of patients with EGFR-mutated and ALK-rearranged NSCLC presenting to our cancer center between 2008 and 2017 and included only patients receiving treatment to four or more BMs in a single radiosurgery session. RESULTS: We identified 35 patients with a median follow-up of 4.1 years. The maximum number of BMs treated in a single radiosurgery session ranged from four to 26 (median number of BM treated per radiosurgery course: 6), and in total over all courses the number ranged from four to 47 (median: 10). The median survival was 3.0 years (4.2 for ALK-rearranged NSCLC; 2.4 for EGFR-mutated NSCLC) from the diagnosis of BM, and survival was comparable regardless of number of radiosurgery courses, number of BMs treated in total, or number of BMs treated in a single radiosurgery session. The mean hippocampal and whole-brain doses were exceedingly low even for patients receiving treatment to more than 10 BMs (1.2 and 0.8 Gy, respectively). Radiosurgery was well tolerated overall and the 5-year rate of freedom from neurologic death was 84%. The 5-year rate of freedom from WBRT was 97%. CONCLUSIONS: Radiosurgery for multiple BMs is controversial, yet patients with EGFR-mutated and ALK-rearranged NSCLC may be uniquely suited to benefit from this approach. These results support single and multiple courses of radiosurgery without WBRT for patients with oncogene-addicted NSCLC with four or more BMs.


Subject(s)
Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Adult , Aged , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Radiosurgery , Young Adult
10.
Support Care Cancer ; 26(6): 1861-1869, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29270829

ABSTRACT

PURPOSE: Despite national recommendations, exercise programs are still not clinically implemented as standard of care for cancer survivors. This investigation examined the effects of a clinically implemented and personalized exercise program on physical fitness, fatigue, and depression in a diverse population of cancer survivors. The association of various participant characteristics on program performance was also examined. METHODS: Data were collected from 170 cancer survivors who had participated in a clinical exercise program. Any cancer type was included and survivors were either undergoing medical treatment or had completed treatment (< 6 months prior to program initiation). Baseline and post program measures of estimated VO2peak, grip strength, fatigue, and depression were compared in survivors who completed the program follow-up. Multiple regressions were performed to investigate the association of age, gender, body mass index (BMI), and medical treatment status on baseline and change scores in outcome measures, as well as program adherence. RESULTS: All measures improved in participants who completed the program (p < 0.01). Age, gender, and BMI were associated with baseline measures of estimated VO2peak and grip strength (p < 0.01), and age was inversely associated with baseline fatigue (p = 0.02). Only BMI was inversely associated with change in estimated VO2peak (p < 0.01). No participant characteristics or baseline measures were predictive of program adherence (p > 0.05). CONCLUSION: This investigation provides evidence that a personalized, clinical exercise program can be effective at improving physical fitness, fatigue, and depression in a diverse population of cancer survivors.


Subject(s)
Cancer Survivors/psychology , Depression/psychology , Fatigue/psychology , Neoplasms/therapy , Physical Fitness/psychology , Quality of Life/psychology , Female , Humans , Male , Middle Aged
11.
Clin Cancer Res ; 23(19): 5711-5719, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28679770

ABSTRACT

Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antigens, Neoplasm/immunology , Camptothecin/analogs & derivatives , Camptothecin/administration & dosage , Cell Adhesion Molecules/immunology , Immunoconjugates/administration & dosage , Small Cell Lung Carcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Camptothecin/adverse effects , Camptothecin/immunology , Cell Adhesion Molecules/antagonists & inhibitors , DNA Topoisomerases, Type I/genetics , DNA Topoisomerases, Type I/immunology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/classification , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Immunoconjugates/adverse effects , Immunoconjugates/chemistry , Kaplan-Meier Estimate , Male , Middle Aged , Molecular Targeted Therapy , Small Cell Lung Carcinoma/immunology , Small Cell Lung Carcinoma/pathology , Topoisomerase I Inhibitors/administration & dosage , Topoisomerase I Inhibitors/adverse effects
12.
J Clin Oncol ; 35(24): 2790-2797, 2017 Aug 20.
Article in English | MEDLINE | ID: mdl-28548889

ABSTRACT

Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points. Results Fifty-four patients were treated. In the response-assessable study population (n = 47), which had a median of three prior therapies (range, two to seven), the ORR was 19%; median response duration, 6.0 months (95% CI, 4.8 to 8.3 months); and clinical benefit rate (complete response + partial response + stable disease ≥ 4 months), 43%. ORR in the intention-to-treat (ITT) population was 17% (nine of 54). Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after immune checkpoint inhibitor therapy. Median ITT progression-free survival was 5.2 months (95% CI, 3.2 to 7.1 months) and median ITT overall survival, 9.5 months (95% CI, 5.9 to 16.7 months). Grade 3 or higher adverse events included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%). One patient developed a transient immune response, despite patients receiving a median of 10 doses. More than 90% of 26 assessable archival tumor specimens were highly positive (2+, 3+) for Trop-2 by immunohistochemistry, which suggests that Trop-2 is not a predictive biomarker for response. Conclusion IMMU-132 was well-tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This ADC should be studied further in this disease and in other patients with Trop-2-expressing tumors.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Camptothecin/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/drug therapy , Immunoconjugates/administration & dosage , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/immunology , Camptothecin/administration & dosage , Carcinoma, Non-Small-Cell Lung/immunology , Cell Adhesion Molecules/biosynthesis , Cell Adhesion Molecules/immunology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Lung Neoplasms/immunology , Male , Middle Aged
13.
J Natl Compr Canc Netw ; 14(11): 1430-1468, 2016 11.
Article in English | MEDLINE | ID: mdl-27799513

ABSTRACT

Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.


Subject(s)
Medical Oncology , Smoking Cessation , Humans , Medical Oncology/standards , Smoking Cessation/statistics & numerical data
15.
Nat Commun ; 7: 11815, 2016 06 10.
Article in English | MEDLINE | ID: mdl-27283993

ABSTRACT

Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment.


Subject(s)
Circulating Tumor DNA/metabolism , Drug Resistance, Neoplasm/drug effects , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Acrylamides/pharmacology , Acrylamides/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Crizotinib , Drug Resistance, Neoplasm/genetics , ErbB Receptors/metabolism , Gene Amplification , Gene Dosage , Genetic Heterogeneity , Humans , Lung Neoplasms/drug therapy , Mutation/genetics , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins c-met/metabolism , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyridines/pharmacology , Pyridines/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Xenograft Model Antitumor Assays
16.
J Clin Pharmacol ; 56(8): 966-73, 2016 08.
Article in English | MEDLINE | ID: mdl-26632033

ABSTRACT

ABT-751 is an orally bioavailable sulfonamide with antimitotic properties. A nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Patients were treated with ABT-751 daily for 7 days (alone) and then began 21-day cycles of treatment with ABT-751 daily and capecitabine twice daily for 14 days plus irinotecan on day 1 intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 after the first 2 dose levels. Because of intolerance to the regimen, a reduced dose of ABT-751 was also explored with reduced-dose and full-dose CAPIRI with bevacizumab. ABT-751 and irinotecan pharmacokinetics, ABT-751 glucuronidation, and protein binding were explored. Twenty-four patients were treated over 5 dose levels. The maximum tolerated dose was ABT-751 125 mg combined with full-dose CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver tests, and febrile neutropenia. ABT-751 is metabolized by UGT1A8 and to a lesser extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN-38 exposure was similar, and SN-38 glucuronide exposure was decreased. Clinically relevant alterations in ABT-751 and irinotecan pharmacokinetics were not observed. Despite modest efficacy, the combination of ABT-751, CAPIRI, and bevacizumab will not be studied further in colorectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Sulfonamides/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/blood , Bevacizumab/blood , Camptothecin/administration & dosage , Camptothecin/blood , Colorectal Neoplasms/blood , Deoxycytidine/administration & dosage , Deoxycytidine/blood , Drug Therapy, Combination , Female , Fluorouracil/administration & dosage , Fluorouracil/blood , Follow-Up Studies , Humans , Male , Middle Aged , Sulfonamides/blood
17.
J Multidiscip Healthc ; 8: 519-26, 2015.
Article in English | MEDLINE | ID: mdl-26664132

ABSTRACT

While most providers support the concept of a multidisciplinary approach to patient care, challenges exist to the implementation of successful multidisciplinary clinical programs. As patients become more knowledgeable about their disease through research on the Internet, they seek hospital programs that offer multidisciplinary care. At the University of Colorado Hospital, we utilize a formal multidisciplinary approach across a variety of clinical settings, which has been beneficial to patients, providers, and the hospital. We present a reproducible framework to be used as a guide to develop a successful multidisciplinary program.

18.
Liver Transpl ; 21(12): 1543-52, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26457885

ABSTRACT

Liver transplantation can provide definitive cure for patients with cirrhosis and hepatocellular carcinoma (HCC) when used appropriately. Advances in the management of HCC have allowed improved control of HCC while waiting for liver transplantation and new approaches to candidate selection particularly with regard to tumor burden and downstaging protocols. Additionally, there have been recent changes in allocation policy related to HCC in the U.S. that cap the HCC MELD exception at 34 points and implement a 6-month delay in a HCC MELD exception. This review examines the U.S. liver transplant allocation policy related to HCC, comprehensively details locoregional therapy options in HCC patients awaiting liver transplantation, and considers the impact of an increasing burden of HCC on future liver graft allocation policy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Patient Selection , Humans
20.
J Natl Compr Canc Netw ; 12(5 Suppl): 745-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24853209

ABSTRACT

The Affordable Care Act (ACA) is a transformational event for health care in the United States, with multiple impacts on health care, the economy, and society. Oncologists and other health care providers are already experiencing many changes-direct and indirect, anticipated and unanticipated. A distinguished and diverse panel assembled at the NCCN 19th Annual Conference to discuss the early phase of implementation of the ACA. The roundtable touched on early successes and stumbling blocks; the impact of the ACA on contemporary oncology practice and the new risk pool facing providers, payers, and patients; and some of the current and future challenges that lie ahead for all.


Subject(s)
Delivery of Health Care/legislation & jurisprudence , Medical Oncology/legislation & jurisprudence , Patient Protection and Affordable Care Act , Humans , United States
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