RESUMEN
Bemarituzumab is an afucosylated monoclonal antibody against FGFR2b (a FGF receptor) with demonstrated monotherapy clinical activity in patients with late-line gastric cancer whose tumors overexpress FGFR2b (NCT02318329). We describe the rationale and design of the FIGHT trial (NCT03343301), a global, randomized, double-blind, placebo-controlled Phase III study evaluating the role of bemarituzumab in patients with previously untreated, FGFR2b-overexpressing advanced gastroesophageal cancer. Patients are randomized in a blinded fashion to the combination of mFOLFOX6 and bemarituzumab or mFOLFOX6 and placebo. Eligible patients are selected based on the presence of either FGFR2b protein overexpression determined by immunohistochemistry or FGFR2 gene amplification determined by circulating tumor DNA. The primary end point is overall survival, and secondary end points include progression-free survival, objective response rate and safety.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos Clínicos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Unión Esofagogástrica/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Biomarcadores de Tumor , Neoplasias Esofágicas/diagnóstico , Unión Esofagogástrica/patología , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Amplificación de Genes , Humanos , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Masculino , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Proyectos de Investigación , Neoplasias Gástricas/diagnósticoRESUMEN
PURPOSE: This phase I trial evaluated the safety, pharmacokinetics, and pharmacodynamics of demcizumab (OMP-21M18), a humanized IgG2 mAb targeting the Notch ligand DLL4 in adult patients with advanced malignancies. EXPERIMENTAL DESIGN: Standard 3+3 design, with demcizumab 0.5, 1, 2.5, or 5 mg/kg weekly or 2.5, 5, or 10 mg/kg every other week, with an expansion cohort at 10 mg/kg every other week. Dose-limiting toxicities (DLT) were assessed during the first 28 days. RESULTS: Fifty-five patients received demcizumab (15 weekly, 18 every other week, 21 expansion cohort, 1 loading dose). No more than one DLT was seen at any dose level. The MTD was not reached for either schedule. Treatment-related adverse events occurring in >10% of patients were hypertension or blood pressure increased (47%), fatigue (31%), anemia (22%), headache (20%), nausea (13%), hypoalbuminemia (11%), dizziness (11%), and dyspnea (11%). One patient dosed at 2.5 mg/kg developed reversible right-sided heart failure after 63 days on treatment and 4 dosed at 10 mg/kg developed congestive heart failure after ≥98 days on treatment. Five patients were hospitalized with bleeding episodes (2 episodes of tumor-associated bleeding). Sixteen of 25 (64%) evaluable patients at 10 mg/kg had evidence of stabilization of disease or response. CONCLUSION: Demcizumab was generally well tolerated at doses ≤5 mg weekly with disease stabilization and decreases in tumor size demonstrating antitumor activity. Hypertension was the most common adverse event that was clearly related to treatment. Prolonged administration was associated with an increased risk of congestive heart failure.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/farmacología , Antineoplásicos/farmacología , Biomarcadores/sangre , Monitoreo de Drogas , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/sangre , Neoplasias/diagnóstico , Células Madre Neoplásicas/metabolismo , Retratamiento , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosAsunto(s)
Oncología Médica/organización & administración , Oncología Médica/normas , Mejoramiento de la Calidad , Calidad de la Atención de Salud , Competencia Clínica , Política de Salud , Humanos , Oncología Médica/tendencias , Neoplasias/terapia , Evaluación de Resultado en la Atención de Salud , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Estados UnidosRESUMEN
This phase 2 study assessed PF-3512676 plus erlotinib in patients with epidermal growth factor receptor-positive advanced non-small cell lung cancer after prior chemotherapy failure. Patients were randomized 1:1 to PF-3512676 (0.20 mg/kg injected subcutaneously once weekly) plus erlotinib (150 mg daily) or erlotinib alone. The primary objective was to estimate progression-free survival (PFS). Patients received PF-3512676 plus erlotinib (n = 18) or erlotinib alone (n = 21). The study was halted because an unplanned interim analysis indicated that large improvement in PFS with addition of PF-3512676 would be unlikely. In the PF-3512676-plus-erlotinib and erlotinib-alone arms, median PFS was 1.6 and 1.7 mo (hazard ratio, 1.00; 95% confidence interval, 0.5-2.0; P = 0.9335), respectively. Salient grade ≥ 3 adverse events in PF-3512676-plus-erlotinib and erlotinib-alone arms were diarrhea (5/0), dyspnea (5/6), fatigue (4/1), other flu-like symptoms (2/0), anemia (2/1), and lymphocytopenia (based on laboratory values, 1/4). Adding PF-3512676 to erlotinib did not show potential for increased progression-free survival over erlotinib alone in patients with advanced recurrent epidermal growth factor receptor-positive non-small cell lung cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/uso terapéutico , Receptor Toll-Like 9/agonistas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Receptores ErbB/biosíntesis , Clorhidrato de Erlotinib , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Oligodesoxirribonucleótidos/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversosRESUMEN
PURPOSE: We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab. EXPERIMENTAL DESIGN: This double-blind, randomized, placebo-controlled phase IIb study (ClinicalTrials.gov NCT00493636) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer and prior bevacizumab treatment. Patients were randomized to chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1,000 mg/m(2) i.v., days 1, 8/21), but later, capecitabine (1,000 mg/m(2) orally twice daily, days 1-14/21) was allowed as an alternative. The primary endpoint was progression-free survival (PFS). RESULTS: One hundred and sixty patients were randomized. More patients received gemcitabine (82.5%) than capecitabine (17.5%). Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [3.4 vs. 2.7 months; HR = 0.65; 95% confidence interval (CI): 0.45-0.95; P = 0.02], time to progression was increased (median, 3.6 vs. 2.7 months; HR = 0.64; 95% CI: 0.44-0.93; P = 0.02), and overall response rate was 19.8% versus 12.7% (P = 0.23). Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71-1.44; P = 0.95). Addition of sorafenib versus placebo increased grade 3/4 hand-foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%). CONCLUSION: The addition of sorafenib to gemcitabine/capecitabine provided a clinically small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Fatiga/inducido químicamente , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Receptor ErbB-2/metabolismo , Enfermedades de la Piel/inducido químicamente , Sorafenib , Estomatitis/inducido químicamente , Resultado del Tratamiento , GemcitabinaRESUMEN
The authors summarize presentations and discussion from the Delivering Affordable Cancer Care in the 21st Century workshop and focus on proposed strategies to improve the affordability of cancer care while maintaining or improving the quality of care.
RESUMEN
PURPOSE: Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC. PATIENTS AND METHODS: Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm). Patients were stratified on the basis of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7). The primary end point was overall response rate (ORR). RESULTS: Overall, 74 patients were enrolled, with 37 in each dosing cohort. ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was 13.5%, median progression-free survival was 9.3 months, and median overall survival was not reached. The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively). The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli. CONCLUSION: Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations.
Asunto(s)
Anilidas/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Quinolinas/administración & dosificación , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anilidas/efectos adversos , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Mutación de Línea Germinal , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas c-met/genética , Quinolinas/efectos adversos , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the efficacy of mitogen-activated protein kinase/extracellular signal-related kinase kinase inhibitor PD-0325901 in advanced non-small cell lung cancer patients who had experienced treatment failure after, or were refractory to, standard systemic therapy. EXPERIMENTAL DESIGN: This open-label, phase II study initially evaluated 15 mg PD-0325901 twice daily administered intermittently (3 weeks on/1 week off; schedule A). As this schedule was not well tolerated, a second schedule was introduced as follows: 5 days on/2 days off for 3 weeks, followed by 1 week off (schedule B). The primary end point was objective response. RESULTS: All patients had received prior systemic therapy (median of two regimens, including epidermal growth factor receptor inhibitors in 26%). Of 13 patients treated on schedule A, three discontinued due to adverse events (blurred vision, fatigue, and hallucinations, respectively). Twenty-one patients received schedule B. Main toxicities included diarrhea, fatigue, rash, vomiting, nausea, and reversible visual disturbances. Hematologic toxicity consisted mainly of mild-to-moderate anemia, without neutropenia. Chemistry abnormalities were rare. Mean (coefficient of variation) PD-0325901 trough plasma concentrations were 100 ng/mL (52%) and 173 ng/mL (73%) for schedules A and B, respectively, above the minimum target concentration established in preclinical studies (16.5 ng/mL). There were no objective responses. Seven patients had stable disease. Median (95% confidence interval) progression-free survival was 1.8 months (1.5-1.9) and overall survival was 7.8 months (4.5-13.9). CONCLUSIONS: PD-0325901 did not meet its primary efficacy end point. Future studies should focus on PD-0325901 schedule, rational combination strategies, and enrichment of patient selection based on mode of action.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Benzamidas/administración & dosificación , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Difenilamina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Adenocarcinoma/patología , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas/farmacocinética , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Difenilamina/administración & dosificación , Difenilamina/farmacocinética , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Distribución Tisular , Resultado del TratamientoRESUMEN
BACKGROUND: Over the past 5 years, the American Society of Clinical Oncology (ASCO) has supported the development of a Web-based quality-reporting tool in response to a recognized need to provide medical oncologists the opportunity to demonstrate the quality of care that they are providing to patients. METHODS: The development of quality measures, their basis in the literature, and the descriptions and organizational structure of the measures are discussed. RESULTS: Specific results are the property of practices and are not shared outside of the practices except in aggregate. The system allows collection of information concerning a wide range of quality measures in a short period of time. In the last data collection period in the fall of 2008, information was submitted concerning 81 measures of quality divided into one required and six optional modules from over 250 practices concerning 15,000 patients. CONCLUSIONS: The timely collection of information on a wide range of quality measures regarding cancer patients can be efficiently collected using a Web-based data collection tool allowing for practice self-examination and comparison with other practices.
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Oncología Médica/métodos , Oncología Médica/normas , Neoplasias/terapia , Garantía de la Calidad de Atención de Salud/métodos , Gestión de la Calidad Total/normas , Humanos , InternetRESUMEN
INTRODUCTION: This phase 1 study was conducted to determine the recommended phase 2 dose of the selective insulin-like growth factor type 1 receptor (IGF-IR) inhibitor figitumumab (F, CP-751,871) given in combination with paclitaxel and carboplatin in patients with advanced solid tumors. METHODS: Patients received paclitaxel 200 mg/m2, carboplatin (area under the curve of 6), and F (0.05-20 mg/kg) q3 weeks for up to six cycles. Patients with objective response or stable disease were eligible to receive additional cycles of single agent F until disease progression. Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints were investigated. RESULTS: Forty-two patients, including 35 with stages IIIB and IV non-small cell lung cancer (NSCLC), were enrolled in eight dose escalation cohorts. A maximum tolerated dose was not identified. Severe adverse events possibly related to F included fatigue, diarrhea, hyperglycemia, gamma glutamyl transpeptidase elevation, and thrombocytopenia (one case each). F plasma exposure parameters increased with dose. Fifteen objective responses (RECIST) were reported, including two complete responses in NSCLC and ovarian carcinoma. Notably, levels of bioactive IGF-1 seemed to influence response to treatment with objective responses in patients with a high baseline-free IGF-1 to IGF binding protein-3 ratio seen only in the 10 and 20 mg/kg dosing cohorts. CONCLUSIONS: F was well tolerated in combination with paclitaxel and carboplatin. Based on its favorable safety, pharmacokinetic, and pharmacodynamic properties, the maximal feasible dose of 20 mg/kg has been selected for further investigation.
Asunto(s)
Anticuerpos Monoclonales/farmacocinética , Antineoplásicos/farmacocinética , Carboplatino/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/farmacocinética , Receptor IGF Tipo 1/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulinas Intravenosas , Inyecciones Intravenosas , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: We conducted a phase II study of combination of the anti-insulin-like growth factor 1 receptor antibody CP-751,871 with paclitaxel and carboplatin (PCI) in advanced treatment-naïve non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomly assigned (2:1) to paclitaxel 200 mg/m(2), carboplatin (area under the plasma concentration-time curve of 6), and CP-751,871 10 to 20 mg/kg (PCI(10), PCI(20)) or paclitaxel and carboplatin alone (PC) every 3 weeks for up to six cycles. PCI(10-20) patients could continue CP-751,871 (figitumumab) treatment after chemotherapy discontinuation. Patients treated with PC experiencing disease progression were eligible to receive CP-751,871 at investigator's discretion. An additional nonrandomized single-arm cohort of 30 patients with nonadenocarcinoma tumor histology receiving PCI(20) was enrolled on completion of the randomized study. RESULTS: A total of 156 patients were enrolled onto the randomized portion of the study. Safety and efficacy information are available for 151 patients (98 patients treated with PCI and 53 patients treated with PC). Forty-eight patients treated with PCI received PCI(10) and 50 patients received PCI(20) in two sequential stages. Twenty of 53 patients treated with PC received CP-751,871 after disease progression. PCI was well tolerated. Fifty-four percent of patients treated with PCI and 42% of patients treated with PC had objective responses. Sixteen of 23 patients assessable for efficacy in the nonrandomized single-arm extension cohort also responded to treatment. Of note, 14 of 18 randomly assigned and 11 of 14 nonrandomly assigned patients treated with PCI with squamous cell carcinoma histology had response to treatment, including nine objective responses in bulky disease. Responses were also observed in two patients with squamous histology receiving CP-751,871 on PC discontinuation. PCI(20)/PC hazard ratio for progression-free survival was 0.8 to 0.56, according to censorship. CONCLUSION: These data suggest that PCI(20) is safe and effective in patients with NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Inmunoglobulinas Intravenosas , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversosRESUMEN
PURPOSE: Edrecolomab (ED) is a murine monoclonal antibody targeting the EpCam antigen. This phase III randomized multicenter trial investigated the benefit of adding ED to fluorouracil (FU) based therapy in patients with stage III colorectal cancer. PATIENTS AND METHODS: Patients with stage III colon cancer were randomly assigned to one of two treatments after curative surgery. Patients in arm 1 received five infusions of ED together with FU-based chemotherapy; patients in arm 2 received FU-based chemotherapy alone. The primary end point was overall survival (OS). RESULTS: One thousand eight hundred thirty-nine patients were randomly assigned; results were analyzed on an intent-to-treat basis. Patient characteristics were well-balanced across treatment arms. Five-year follow-up has been completed. Patients randomly assigned to ED plus FU-based therapy showed a 5-year survival rate of 69.6% while for patients receiving FU-based therapy, the rate was 68.2%. The hazard ratio for death with ED plus FU-based therapy compared to FU-based therapy was 0.896 (95% CI, 0.752 to 1.068), which was not statistically significant (P = .220). The adverse effect profiles of the two treatment arms were similar, with the main adverse effects being diarrhea, abdominal pain, and nausea. Anaphylaxis occurred in fewer than 1% of patients receiving ED. CONCLUSION: For patients with stage III colon cancer, the addition of ED to FU-based therapy had no statistically significant effect on OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Agencias Internacionales , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Calidad de Vida , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
We provide a brief review of the use of quality measures to assess supportive care in the medical oncology office. Specifically, we discuss the development and implementation of supportive care measures in the Quality Oncology Practice Initiative (QOPI), a voluntary quality measurement and improvement program of the American Society of Clinical Oncology. QOPI has demonstrated that medical oncologists voluntarily engage in self-assessment and often select measures related to supportive care for measurement and improvement. Results to date have demonstrated that there is room for improvement in this domain. Because supportive care measures appropriate for use through structured chart review in the outpatient oncology setting are not generally available in the published literature, measures have been developed and tested through the program. Additional measures are in development for implementation in QOPI in 2008.
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Oncología Médica/normas , Pautas de la Práctica en Medicina , Evaluación de Programas y Proyectos de Salud/métodos , Garantía de la Calidad de Atención de Salud/métodos , Apoyo Social , Humanos , Oncología Médica/métodos , Oncología Médica/tendencias , Garantía de la Calidad de Atención de Salud/tendenciasRESUMEN
PURPOSE: The Quality Oncology Practice Initiative (QOPI) became available to all American Society of Clinical Oncology member physicians in 2006 as a voluntary medical oncology practice-based quality measurement and improvement project. QOPI assesses practice performance for a series of evidence- and consensus-based process measures, relying on practices to complete structured chart reviews and submit data via a secure Web-based portal. METHODS: This analysis focused on the 71 practices that participated in both the March and September 2006 data collections (7,624 charts abstracted in March and 10,240 in September). Among 33 measures common to both collections, five measures were closely correlated, and 28 are included in the final analysis. Composite scores were created for six different domains of care. Statistical significance was tested on both absolute changes and relative changes (relative failure reduction) of quality measures from baseline to follow-up and between the lower quartile and all other quartiles. RESULTS: Practice performance on individual measures varied between 18.8% and 98.6%. Mean overall performance as measured by a composite score increased from 78.7% in March to 82.3% in September (P < .05). Improvement was most marked among practices originally performing in the bottom quartile. Using a composite score, the absolute and relative performance for the bottom quartile improved by 27% and 35%, respectively, statistically superior to that of all others. CONCLUSION: Practices that participated in QOPI demonstrated improved performance in self-reported process measures, with the greatest improvement demonstrated in initially low-performing practices.
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Oncología Médica/organización & administración , Pautas de la Práctica en Medicina/organización & administración , Calidad de la Atención de Salud/organización & administración , Evaluación del Rendimiento de Empleados/clasificación , Medicina Basada en la Evidencia , Oncología Médica/normas , Vigilancia de la Población , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Calidad de la Atención de Salud/normas , Estudios Retrospectivos , Estados UnidosRESUMEN
PURPOSE: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis. RESULTS: Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for >or= 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during >or= 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions. CONCLUSION: Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Carcinoma/secundario , Indoles/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirroles/uso terapéutico , Administración Oral , Adulto , Anciano , Antraciclinas/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/mortalidad , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Carcinoma/clasificación , Esquema de Medicación , Fatiga/inducido químicamente , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Hematológicas/inducido químicamente , Humanos , Indoles/efectos adversos , Indoles/sangre , Persona de Mediana Edad , Pirroles/efectos adversos , Pirroles/sangre , Sunitinib , Tasa de Supervivencia , Taxoides/administración & dosificaciónRESUMEN
GOALS OF WORK: The present study sought to determine the prevalence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) across ten community oncology settings. The effect of CINV on quality of life (QOL) was also evaluated. MATERIALS AND METHODS: Cancer patients who were scheduled for their first cycle of a new chemotherapy regimen were recruited from ten community oncology clinics. Study participants recorded occurrence of CINV by completing a daily diary each day for the first 8 days after treatment during each cycle and the Functional Living Index-Emesis (FLIE) before chemotherapy, at the end of day 1 and day 6 after chemotherapy. Mixed model regression analysis was used to explore the association between occurrence of CINV at cycle 1 and subsequent cycles and its impact on patient QOL. MAIN RESULTS: One hundred and fifty-one patients provided information for at least one cycle. During cycle 1, only 33% had neither acute nor delayed CINV. Of the 36% patients who developed acute CINV, 8% developed acute CINV only. Of the 59% who developed delayed CINV, 53% reported delayed only and 47% reported acute and delayed CINV. A similar pattern was seen at cycles 2 and 3. Experience of CINV at cycle 1 was associated with the development of CINV at cycles 2 and 3. Occurrence of CINV significantly interfered with patient QOL as assessed by the FLIE. CONCLUSIONS: CINV remained a substantial problem for patients receiving chemotherapy in this community-based sample, especially delayed CINV. CINV significantly interfered with patient QOL and daily functioning.
Asunto(s)
Antineoplásicos/efectos adversos , Náusea/inducido químicamente , Calidad de Vida , Vómitos/inducido químicamente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/epidemiología , Neoplasias/tratamiento farmacológico , Análisis de Regresión , Encuestas y Cuestionarios , Estados Unidos/epidemiología , Vómitos/epidemiologíaRESUMEN
PURPOSE: To evaluate the toxicity profile and pharmacological properties of oral CP-547,632 alone and in combination with paclitaxel and carboplatin administered every 3 weeks, and to assess efficacy as measured by the objective response and progressive disease rates of oral CP-547,632 administered in combination with paclitaxel and carboplatin. PATIENTS AND METHODS: Patients with stage IIIB/IV or recurrent non-small cell lung cancer receiving first-line chemotherapy were treated with oral daily CP-547,632 in combination with paclitaxel 225 mg/m(2) and carboplatin AUC = 6 every 3 weeks. Pharmacokinetics parameters for CP-547,632 and paclitaxel were determined independently and during co-administration. RESULTS: Seventy patients were enrolled and 68 patients were treated, 37 in phase 1 and 31 in phase 2 (14 with the combination and 17 with chemotherapy alone). Dose-limiting toxicity of CP-547,632 250 mg by mouth daily in combination with paclitaxel and carboplatin was grade 3 rash and grade 3 diarrhea despite medical intervention. CP-547,632 did not significantly affect the pharmacologic profiles of paclitaxel and carboplatin. No subject had CR. In phase I, seven subjects (22.6%) had a confirmed partial response. In phase II, four subjects (28.6%) receiving CP-547,632 plus chemotherapy had a confirmed partial response. In the phase II chemotherapy alone group, four subjects (25%) had a confirmed partial response. CONCLUSION: The combination of CP-547,632 and paclitaxel and carboplatin was well-tolerated at doses up to 200 mg by mouth daily. Dose-limiting toxicity of CP-547,632 at 250 mg consisted of diarrhea and rash. CP-547,632 did not increase the objective response rate to chemotherapy alone in patients with advanced non-small cell lung cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Área Bajo la Curva , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carboplatino/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/patología , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Exantema/inducido químicamente , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Semivida , Enfermedades Hematológicas/inducido químicamente , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/farmacocinética , Pronóstico , Tiazoles/administración & dosificación , Tiazoles/efectos adversos , Tiazoles/farmacocinética , Resultado del Tratamiento , Urea/administración & dosificación , Urea/efectos adversos , Urea/análogos & derivados , Urea/farmacocinéticaRESUMEN
PURPOSE: The Quality Oncology Practice Initiative (QOPI) is a practice-based system of quality self-assessment sponsored by the participants and the American Society of Clinical Oncology (ASCO). The process of quality evaluation, development of the pilot questionnaire, and preliminary results are reported. METHODS: Physicians from seven oncology groups developed medical record abstraction measures based on practice guidelines and consensus-supported indicators of quality care. Each practice completed two rounds of records review and received practice and aggregate results. Mean frequencies of responses for each indicator were compared among practices. RESULTS: Participants universally, if informally, find QOPI helpful, and results show statistically significant variation among practices for several indicators, including assessing pain in patients close to death, documentation of informed consent for chemotherapy, and concordance with granulocytic and erythroid growth factor administration guidelines. Measures with universally high concordance include the use of serotonin antagonist antiemetics according to the ASCO guideline; the presence of a pathology report in the record; the use of chemotherapy flow sheets; and adherence to standard chemotherapy recommendations for patients with certain stages of breast, colon, and rectal cancer. Concordance with quality indicators significantly changed between survey rounds for several measures. CONCLUSION: Pilot results indicate that the QOPI process provides a rapid and objective measurement of practice quality that allows comparisons among practices and over time. It also provides a mechanism for measuring concordance with published guidelines. Most importantly, it provides a tool for practice self-examination that can promote excellence in cancer care.
Asunto(s)
Adhesión a Directriz , Oncología Médica/normas , Guías de Práctica Clínica como Asunto , Garantía de la Calidad de Atención de Salud/métodos , Sociedades Médicas , Recolección de Datos , Humanos , Consentimiento Informado , Registros Médicos/estadística & datos numéricos , Dolor/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Cuidado TerminalRESUMEN
BACKGROUND: An aprepitant (APR) regimen was evaluated for prevention of nausea and emesis due to moderately emetogenic chemotherapy (MEC) over multiple cycles. METHODS: The authors performed a randomized, double-blind study. Eligible patients with breast carcinoma were naïve to emetogenic chemotherapy and treated with cyclophosphamide alone or with doxorubicin or epirubicin. Patients were randomized to receive either an APR regimen (Day 1: APR 125 mg, ondansetron [OND] 8 mg, and dexamethasone [DEX] 12 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: APR 80 mg every day) or a control regimen (Day 1: OND 8 mg and DEX 20 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: OND 8 mg twice per day). Data on nausea, emesis, and use of rescue medication were collected. The primary end point was the proportion of patients with a complete response (CR; no emesis or use of rescue therapy) in Cycle 1. Efficacy end points for the multiple-cycle extension were the probabilities of a CR in Cycles 2-4 and a sustained CR rate across multiple cycles. RESULTS: Of 866 patients randomized, 744 (85.9%) entered the multiple-cycle extension, and 650 (75.1%) completed all 4 cycles. Overall, the CR was greater with the APR regimen over the 4 cycles: 53.8% versus 39.4% for Cycle 2, 54.1% versus 39.3% for Cycle 3, and 55.0% versus 38.4% for Cycle 4. The cumulative percentage of patients with a sustained CR over all 4 cycles was greater with the APR regimen (P = 0.017). CONCLUSIONS: The APR regimen was more effective than a control regimen for the prevention of nausea and emesis induced by MEC over multiple chemotherapy cycles.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Morfolinas/administración & dosificación , Náusea/prevención & control , Neoplasias/tratamiento farmacológico , Vómitos/prevención & control , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aprepitant , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dosis Máxima Tolerada , Morfolinas/efectos adversos , Náusea/inducido químicamente , Neoplasias/diagnóstico , Probabilidad , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo , Resultado del Tratamiento , Vómitos/inducido químicamenteRESUMEN
PURPOSE: This is the first study in which the NK(1)-receptor antagonist, aprepitant (APR), was evaluated for the prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy. PATIENTS AND METHODS: Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide +/- doxorubicin or epirubicin. Patients were randomly assigned to either an aprepitant regimen (day 1, APR 125 mg, ondansetron (OND) 8 mg, and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, APR 80 qd) [DOSAGE ERROR CORRECTED] or a control regimen (day 1, OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, OND 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary. The primary efficacy end point was the proportion of patients with complete response, defined as no vomiting and no use of rescue therapy, during 120 hours after initiation of chemotherapy in cycle 1. The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis questionnaire. RESULTS: Of 866 patients randomized, 857 patients (99%) were assessable. Overall complete response was greater with the aprepitant regimen than with the control regimen (50.8% v 42.5%; P = .015). More patients in the aprepitant group reported minimal or no impact of CINV on daily life (63.5% v 55.6%; P = .019). Both treatments were generally well tolerated. CONCLUSION: The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide.