RESUMEN
BACKGROUND: Despite histological and molecular differences between invasive lobular carcinoma (ILC) and invasive carcinoma of no special type, according to national treatment guidelines no distinction is made regarding the use of (neo)adjuvant chemotherapy. Studies on the long-term outcome of chemotherapy in patients with ILC are scarce and show inconclusive results. METHODS: All patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative ILC with an indication for chemotherapy treated with adjuvant endocrine therapy were selected from the Erasmus Medical Center Breast Cancer database. Cox proportional hazards models were used to estimate the effect of chemotherapy on recurrence-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: A total of 520 patients were selected, of whom 379 were treated with chemotherapy and 141 were not. Patients in the chemotherapy group were younger (51 vs. 61 years old; p < .001), had a higher T status (T3+, 33% vs. 14%; p < .001), and more often had lymph node involvement (80% vs. 49%; p < .001) in comparison to the no-chemotherapy group. After adjusting for confounders, chemotherapy treatment was not associated with better RFS (hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.63-2.31), BCSS (HR, 1.24; 95% CI, 0.60-2.58), or OS (HR, 0.97; 95% CI, 0.56-1.66). This was also reflected by adjusted Cox survival curves in the chemotherapy versus no-chemotherapy group for RFS (75% vs. 79%), BCSS (80% vs. 84%), and OS (72% vs. 71%). CONCLUSIONS: Chemotherapy is not associated with improved RFS, BCSS, or OS for patients with ER+/HER2- ILC treated with adjuvant endocrine therapy and with an indication for chemotherapy.
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Neoplasias de la Mama , Carcinoma Lobular , Humanos , Persona de Mediana Edad , Femenino , Neoplasias de la Mama/patología , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/patología , Estudios Retrospectivos , Mama/patología , Quimioterapia Adyuvante , Receptor ErbB-2/metabolismo , Adyuvantes Inmunológicos , Factores Inmunológicos/uso terapéuticoRESUMEN
BACKGROUND: Endoxifen is the most important active metabolite of tamoxifen. Several retrospective studies have suggested a minimal or threshold endoxifen systemic concentration of 14-16 nM is required for a lower recurrence rate. The aim of this study was to investigate the feasibility of reaching a predefined endoxifen level of ≥ 16 nM (5.97 ng/mL) over time using therapeutic drug monitoring (TDM). METHODS: This prospective open-label intervention study enrolled patients who started treatment with a standard dose of tamoxifen 20 mg once daily for early breast cancer. An outpatient visit was combined with a TDM sample at 3, 4.5, and 6 months after initiation of the tamoxifen treatment. The tamoxifen dose was escalated to a maximum of 40 mg if patients had an endoxifen concentration < 16 nM. The primary endpoint of the study was the percentage of patients with an endoxifen level ≥ 16 nM at 6 months after the start of therapy compared with historical data, in other words, 80% of patients with endoxifen levels ≥ 16 nM with standard therapy. RESULTS: In total, 145 patients were included. After 6 months, 89% of the patients had endoxifen levels ≥ 16 nM, compared with a literature-based 80% of patients with endoxifen levels ≥ 16 nM at baseline (95% confidence interval 82-94; P = 0.007). In patients with an affected CYP2D6 allele, it was not always feasible to reach the predefined endoxifen level of ≥ 16 nM. No increase in tamoxifen-related adverse events was reported after dose escalation. CONCLUSION: This study demonstrated that it is feasible to increase the percentage of patients with endoxifen levels ≥ 16 nM using TDM. TDM is a safe strategy that offers the possibility of nearly halving the number of patients with endoxifen levels < 16 nM.
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Neoplasias de la Mama , Tamoxifeno , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Citocromo P-450 CYP2D6/metabolismo , Monitoreo de Drogas , Femenino , Hormonas , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Tamoxifeno/administración & dosificación , Tamoxifeno/efectos adversos , Tamoxifeno/análogos & derivadosRESUMEN
BACKGROUND: Radium-223 (Ra-223), an alpha-emitting radiopharmaceutical, established an improved overall survival and health-related quality of life (HRQoL) in symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients. However, effects on pain were not specifically evaluated. Here we assess integrated HRQoL, pain, and opioid use in a contemporary, more extensively pretreated, symptomatic and asymptomatic mCRPC population. METHODS: mCRPC patients scheduled for Ra-223 treatment were included and analyzed for HRQoL, pain, and opioid use, using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires and recording of opioid use and dosage, respectively. Primary outcome measure was the percentage of patients experiencing a complete pain response (score of 0 on the BPI-SF Worst pain item and no increase in daily use of analgesics). A complete or partial pain response (better BPI-SF score and decrease in opioid use) and a better or no change in HRQoL was evaluated as an integrated overall clinical response (IOCR). Secondary endpoints included the time to pain progression (TPP) and Total FACT-P deterioration (TTFD), defined as time from first Ra-223 treatment to clinical meaningful increase in BPI-SF Worst pain item score and Total FACT-P score, respectively. RESULTS: This registry included 300 patients, of whom 105 (35%) were evaluable for FACT-P and BPI-SF during Ra-223 treatment. Forty-five (43%) patients had pain at baseline (PAB) (BPI-SF Worst pain score 5-10 points) and 60 (57%) had no pain at baseline (no-PAB) (BPI-SF Worst pain score 0-4 points). Complete pain response was achieved in 31.4% of the patients, while 58% had an IOCR. The median TTP and TTFD were 5.6 and 5.7 months, respectively, while the difference between PAB and no-PAB patients was not significant. CONCLUSIONS: In contemporary, extensively pretreated mCRPC patients, Ra-223 treatment induced complete pain responses while integrated analysis of HRQoL, pain response, and opioid use demonstrated that the majority of patients derive clinical benefit.
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Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Analgésicos Opioides/efectos adversos , Humanos , Masculino , Dolor/etiología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Calidad de Vida , Radio (Elemento)/efectos adversosRESUMEN
BACKGROUND: Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea-active ingredient epigallocatechin-3-gallate (EGCG)-is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. METHODS: In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0-24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration-time curves. RESULTS: No difference was found in geometric mean endoxifen AUC0-24h in the period with green tea versus tamoxifen monotherapy (- 0.4%; 95% CI - 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (- 2.8%; - 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; - 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. CONCLUSIONS: This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged.
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Neoplasias de la Mama , Catequina , Neoplasias de la Mama/tratamiento farmacológico , Catequina/análisis , Estudios Cruzados , Suplementos Dietéticos , Femenino , Humanos , Tamoxifeno/análogos & derivados , TéRESUMEN
The ALSYMPCA study established a 3.6 month Overall Survival (OS) benefit in metastatic Castration Resistant Prostate Cancer (mCRPC) patients treated with Radium-223 dichloride (Ra-223) over placebo. Here we report clinical outcomes of Ra-223 treatment in a nonstudy population. In this prospective registry, patients from 20 Dutch hospitals were included prior to Ra-223 treatment. Clinical parameters collected included previous treatments and Adverse Events. Primary outcome was 6 months Symptomatic Skeletal Event (SSE)-free survival, while secondary outcomes included Progression-Free Survival (PFS) and Overall Survival (OS). Of the 305 patients included, 300 were evaluable. The mean age was 73.6 years, 90% had ≥6 bone metastases and 74.1% were pretreated with Docetaxel, 19.5% with Cabazitaxel and 80.5% with Abiraterone and/or Enzalutamide. Of all patients, 96.7% were treated with Ra-223 and received a median of 5 cycles. After a median follow-up of 13.2 months, 6 months SSE-free survival rate was 83%, median PFS was 5.1 months and median OS was 15.2 months. Six months SSE-free survival rate and OS were comparable with those reported in ALSYMPCA. "Previous Cabazitaxel treatment" and "bone-only metastases" were independent predictors of a shorter and longer PFS, respectively, while above-median LDH and "bone-only metastases" were independent predictors of shorter and longer OS, respectively. Toxicity was similar as reported in the ALSYMPCA trial. These results suggest that in a nonstudy population, Ra-223 treatment is well-tolerated, equally effective as in the ALSYMPCA population and that patients not previously treated with Cabazitaxel benefit most from Ra-223.
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Antineoplásicos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/terapia , Radio (Elemento)/uso terapéutico , Sistema de Registros/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Androstenos/uso terapéutico , Benzamidas , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Quimioradioterapia/métodos , Docetaxel/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Nitrilos , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Estudios Prospectivos , Taxoides/uso terapéuticoAsunto(s)
Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Ecocardiografía Tridimensional/métodos , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Ecocardiografía Tridimensional/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/tendencias , Reproducibilidad de los Resultados , Estados UnidosRESUMEN
Purpose: Forty-seven percent of patients in the pivotal trial of cabazitaxel reported diarrhea of any grade. Aiming to reduce the incidence of diarrhea, we studied the effects of budesonide on the grade of cabazitaxel-induced diarrhea during the first two treatment cycles.Experimental Design: Between December 2011 and October 2015, 246 metastatic castration-resistant prostate cancer patients were randomized to receive standard-of-care cabazitaxel 25 mg/m2 every 3 weeks plus prednisone 10 mg/day (group CABA) or same dose/schedule of cabazitaxel with concomitant budesonide 9 mg daily during the first two treatment cycles (group BUD). The occurrence of diarrhea was reported by physicians and by patients in a diary. χ2 tests were used to compare incidence numbers. An intention-to-treat principle was used.Results: In the phase II trial, 227 patients were evaluable. Grade 2-3 diarrhea occurred in 35 patients (15%) and grade 4 diarrhea was not reported. The incidence of grade 2-3 diarrhea was comparable in both treatment groups: 14 of 113 patients in group CABA (12%) versus 21 of 114 patients in group BUD (18%; P = 0.21). Seven patients were admitted to the hospital with diarrhea (n = 5 group CABA vs. n = 2 group BUD). PSA response was seen in 30% of patients and was not affected by budesonide coadministration (P = 0.29). Also, other toxicities were not affected by budesonide coadministration.Conclusions: The incidence of cabazitaxel-induced diarrhea was notably lower than reported in the TROPIC trial and appears manageable in routine clinical practice. Budesonide coadministration did not reduce the incidence or severity of cabazitaxel-induced diarrhea. Clin Cancer Res; 23(7); 1679-83. ©2016 AACR.
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Budesonida/administración & dosificación , Diarrea/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Anciano , Diarrea/inducido químicamente , Diarrea/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata Resistentes a la Castración/complicaciones , Neoplasias de la Próstata Resistentes a la Castración/patología , Taxoides/efectos adversos , Resultado del TratamientoAsunto(s)
Vesícula/inducido químicamente , Carcinoma de Células Renales/terapia , Medios de Contraste/efectos adversos , Erupciones por Medicamentos/etiología , Dermatosis de la Mano/inducido químicamente , Neoplasias Renales/terapia , Ácidos Triyodobenzoicos/efectos adversos , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/secundario , Humanos , Indazoles , Neoplasias Renales/patología , Masculino , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
Thrombocytopenia is a well-documented adverse reaction of sunitinib. Thrombocytopenia was observed in a patient with metastatic renal clear-cell carcinoma undergoing sunitinib treatment. Platelet count in an ethylenediaminetetraacetic acid (EDTA) sample was 19 × 10(9)/l. To exclude pseudothrombocytopenia (PTCP), a platelet count in citrate-anticoagulated blood was performed, showing a platelet count of 6 × 10(9)/l. Due to the apparent thrombocytopenia, the patient received platelet concentrates. Subsequent analyses revealed PTCP whereby platelet clumping was most abundant in citrate - followed by EDTA- and heparin-anticoagulated blood samples. This effect was partially reversed after placing blood samples at 37°C. The IgM antiplatelet autoantibodies responsible for in vitro agglutination are temperature and multianticoagulant dependent and did not react to amikacin pre-supplementation. Remarkably, the antibody revealed specificity to platelet antigens other than GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIV, and GPV. After 16 days of discontinuing sunitinib, no PTCP and no platelet reactive antibodies could be detected. We report a case of PTCP with clear time-relation with sunitinib, strongly suggesting the mechanism to be sunitinib dependent. Since this finding has not been described before, non-recognition of PTCP during sunitinib treatment might lead to dose reduction or unwarranted therapy.