RESUMEN
Systemic inflammation response (SIR) plays a role in predicting prognosis of patients with metastatic colorectal cancer (mCRC). Chemotherapy-induced neutropenia has been suggested as another evaluable prognostic and predictive factor. This is a retrospective analysis of derived neutrophil-to-lymphocyte ratio (dNLR) and its reduction > 10% after the first cycle of chemotherapy (R10) in a monoinstitutional series of patients with mCRC receiving a first-line and a second-line cytotoxic chemotherapy. The effects of the neutrophil-related variables on overall survival (OS) and on chemotherapy activity were analyzed. One hundred twenty-eight patients were selected. A relationship of dNLR with OS was evident at both time points, but disappeared after multivariate analysis, whereas R10 was independent prognostic factor only after second-line chemotherapy in multivariate analysis. A dNLR reduction > 10% before the second cycle predicts OS and disease control from second-line chemotherapy in patients with mCRC, in particular among patients with right-sided tumors and synchronous metastases.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/mortalidad , Linfocitos/patología , Neutrófilos/patología , Neoplasias Peritoneales/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Systemic inflammation response (SIR)-related variables are controversial as predictive variables. METHODS: Patients with metastatic pancreatic adenocarcinoma (mPDAC) receiving chemotherapy were identified, three SIR-related variables and the relationships between each of them with overall survival (OS) were analysed. RESULTS: Of 129 patients receiving chemotherapy, 97 had metastases. A significant relationship between SIR and OS has been documented. Each of the SIR-related variables retained its independent prognostic role after multivariate analysis, whereas tri-linear peripheric blood-cell score (TRIS) appeared as the most reliable predictive parameter. CONCLUSIONS: Among patients with mPDAC receiving chemotherapy, SIR is prognostic and could predict the effectiveness of chemotherapy.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Inflamación/etiología , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Pronóstico , Análisis de Supervivencia , Neoplasias PancreáticasRESUMEN
BACKGROUND: Many reports suggest more activity of cytotoxic chemotherapy among patients with metastatic colorectal cancer (mCRC) who experience neutropenia, but it is not clear whether this finding is related to drug effect alone. The aim of the study is to identify the characteristics of patients whose peripheral blood cell kinetics (PBCK) is related to the outcome. METHODS: The study is a retrospective analysis of patients with mCRC who had received first-line chemotherapy at Sanremo hospital from 2010 to 2015, evaluating seventeen baseline variables, six related to systemic inflammatory response activation (SIRA), and six to peripheral blood cell kinetics after one cycle. The relationship of peripheral blood cell kinetics variables was evaluated by tumor location, SIRA, and timing of metastases. RESULTS: Among 203 eligible patients, only four variables were able to independently predict survival (age, CA 19-9, number of drugs, chemotherapy-induced leukopenia after the first cycle or CIL-1). After stratification by tumor location or by SIRA, no relationship of PBCK variables with prognosis was present. On the contrary, after stratification by timing of metastasis, the prognostic role of CIL-1 was evident among patients with metachronous metastases, particularly among those with low SIRA and colon tumors, whereas the leukocyte reduction after the first cycle (WR) predicted longer survival of patients with synchronous metastases and a previous resection of the primary tumor (PTR). CONCLUSIONS: Absolute leukocyte reduction (CIL-1) predicts a better OS of patients with metachronous metastases, whereas relative leukocyte reduction (WR) could be prognostic among patients with synchronous metastases who have received PTR.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Humanos , Cinética , Leucocitos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Recently, measures of tumor growth kinetics calculated by carbohydrate antigen 19-9 (CA 19-9) determinations after cytotoxic chemotherapy (CHT) have been reported as effective prognostic indicators in locally-advanced unresectable and metastatic pancreatic adenocarcinoma (mPDAC). The study aims to evaluate the prognostic role of tumor kinetics measured by CA 19-9 in patients with mPDAC, measuring it by three different ways. METHODS: Patients with mPDAC receiving a first-line CHT between 2009 and 2017 were identified, and those for whom CA 19-9 data were available were enrolled. Three CA 19-9-related variables were calculated: CA 19-9 related reduction rate (RR) and tumor growth rate (G), after 8 weeks of CHT, tumor growth and inflammation index (TGII), after 90 days of CHT. The relationships with the outcome were analysed, and a Cox model has been build with each of the three variables. RESULTS: Of 118 patients only 48 were eligible for the analysis. RR, G, or TGII appear as significant prognostic factors, and, after multivariate analysis, a reduction rate of 20% the baseline or more was associated with good survival (HR 0.321; CIs 0.156-0.661) as well as a G > -0.4%/day (HR 2.114; CIs 1.034-4.321), whereas TGII >190 was not correlated with the outcome (HR 1.788; CIs 0.789-4.055). CONCLUSIONS: In patients with mPDAC, after 8 weeks of first-line CHT, CA 19-9-related tumor reduction or growth rate appear as valuable prognostic factors.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antígeno CA-19-9/sangre , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Femenino , Humanos , Inflamación/patología , Cinética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: The introduction of new drugs and multimodal treatments for the management of patients with metastatic colorectal cancer (mCRC) has reduced the importance of time-to-event endpoints and reported the attention on the response-related endpoints. Furthermore, the prognostic role of the surgical scores before the resection of metastases has not been confirmed for multimodal treatments. The purpose of this research is to perform a meta-analysis of the studies that evaluated the relationship between carcinoembryonic antigen (CEA) response and outcome in patients with mCRC receiving systemic chemotherapy. METHODS: A systematic review of the literature on two databases and a selection of studies that evaluated the relationship between CEA response and outcome were performed according to predefined criteria. After, three meta-analyses were carried out on the selected studies, each for each outcome variable. RESULTS: Nineteen studies have been selected. Fourteen studies (1475 patients) have documented a close association between radiological response and CEA response (odds ratio (OR), 9.03; confidence intervals (CIs), 5.14-15.87; I2 statistic (I2), 72%). Four studies have reported a longer progression-free survival for patients with a CEA response (hazard ratio (HR), 0.73; CIs, 0.64-0.83; I2, 23%). Finally, 10 studies (13 study cohorts) have shown a strong relationship between CEA response and overall survival (OS) (HR, 0. 62; CIs, 0.55-0.70; I2, 35%). CONCLUSIONS: CEA response merits further investigation as a surrogate endpoint of clinical trials of first-line medical therapy of patients with mCRC, and should be studied as a prognostic factor for those patients who are candidates for multimodal treatment strategies.
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Antígeno Carcinoembrionario/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Humanos , Metástasis de la Neoplasia , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: Early tumor shrinkage (ETS) is a response-related endpoint of clinical trials of chemotherapy (CHT) of patients with metastatic colorectal cancer (mCRC). It identifies a dimensional reduction of tumor size by at least 20-30% after 6-8 weeks of CHT. METHODS: A literature search of randomized trials of systemic treatment including CHT with or without antiangiogenics or anti-EGFR inhibitors in patients with mCRC has been conducted, and studies reporting the results of the relationship of ETS with overall survival (OS) and progression-free survival (PFS) were selected. RESULTS: Twelve trials, including 3117 patients, have been included; all data were retrospective and only 72% of the enrolled patients have been evaluated for ETS. Two meta-analyses, each including 20 study cohorts from the selected 12 trials, reported a strong relationship of ETS with OS (HR 0.62; CIs 0.55-0.69) and of ETS with PFS (HR 0.66; CIs 0.60-0.73). However, both meta-analyses displayed a high level of heterogeneity. Among nine possible moderators, three variables (median age, surgery of metastases, and publication year) were able to explain at least a part of this heterogeneity. CONCLUSION: ETS is a simple and interesting intermediate endpoint for clinical practice and future trials of medical treatments of patients with mCRC, but a large prospective analysis and validation are mandatory.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Tumor radiologic response after systemic chemotherapy has been used as endpoint of trials of patients with metastatic colorectal cancer (mCRC), which can report the best overall response rate (ORR) and the disease control rate (DCR) by RECIST criteria as well as the early tumor shrinkage (ETS). The present study perform a trial-level analysis to verify whether such response-related endpoints are predictive of overall survival (OS). METHODS: After a systematic search, randomized clinical trials (RCTs) were selected each time they evaluated the three response endpoints and progression-free survival (PFS). Two arms per trial were selected, and the correlation between the difference in each endpoint and the difference in OS was calculated. The analysis then evaluated the effects of treatment on ∆ORR, or ∆DCR, ∆ETS, ∆PFS, and on ∆OS, using separate linear regressions for each of them, and the proportion of variability explained (R2trial) on OS for each of the four endpoints was calculated. RESULTS: The systematic review of the literature led to the selection of 12 RCTs, 7 phase-3 and 5 phase-2. ETS reported a different performance in the entire sample compared to phase-3 trials (R2trial = 0.172 vs. 0.842), differently from DCR (R2trial = 0.541 vs. 0.816) and ORR (R2trial = 0.349 vs. 0.740). Surprisingly, PFS predicted OS with a weak correlation, which was not significant in the subgroup of phase-3 studies (R2trial = 0.455 vs. 0.466). CONCLUSION: The results of the present trial-level analysis report a good performance of two response-related endpoints, DCR and ETS, and suggest that they could be differently used depending on the setting of disease and the type of medical treatment.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Humanos , Modelos Lineales , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: Defining the reliability of cancer antigen-125-related kinetics criteria versus Gynecologic Cancer Inter Group criteria in predicting the tumor outcome after chemotherapy in patients with recurrent ovarian cancer. METHODS: A retrospective monoinstitutional assessment of CA125-related versus Gynecologic Cancer Inter Group-related parameters was performed after cytotoxic chemotherapy in patients with metastatic ovarian cancer treated from 2006 to 2011. A correlation analysis between the response and progression measurements has been performed, and the outcome has been reported. RESULTS: Among 42 eligible patients, tumor response and progression calculated by CA125 kinetics, with tumor response at 8 weeks and specific growth rate at progression, exhibited a significant correlation with progression-free and overall survival, similar to tumor response and progression by Gynecologic Cancer Inter Group criteria. CONCLUSIONS: The tumor response at 8 weeks higher than 1.77 appears to be a good surrogate of clinical response, whereas the definition of progression when CA125 increases above a value double than the nadir suggests a similar performance of growth rate at progression versus Gynecologic Cancer Inter Group criteria and warrants further investigation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Antígeno Ca-125/metabolismo , Carcinoma/tratamiento farmacológico , Proteínas de la Membrana/metabolismo , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Carcinoma/inmunología , Carcinoma/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Cinética , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Neutrophil-to-lymphocyte ratio is suggested as a prognostic and predictive factor for patients with rectal cancer. The purpose of the current meta-analysis is to evaluate the relationship between neutrophil-lymphocyte ratio (NLR) and the outcome of patients, with rectal cancer receiving chemoradiation and surgery. METHODS: A systematic review on two databases and a selection of studies were done. Thereafter, two meta-analyses were performed, evaluating the relationship of baseline NLR with overall survival (OS) and disease-free survival (DFS). RESULTS: Thirty-one retrospective studies were selected. Twenty-six studies have documented a significant relationship of NLR to OS (HR 2.05, CI 1.66-2.53), whereas 23 studies have reported a weaker but significant relationship of NLR to DFS (HR 1.78, CI 1.49-2.12). Among the moderator variables, a possible effect for age and sex on the relationship of NLR with DFS is suggested. CONCLUSIONS: Baseline NLR >3 is a simple and reproducible prognostic factor, with a more consistent effect in the elderly. It could be a reliable variable to support clinicians in defining personalized treatment strategies, even though a standardization of the cutoff and a better characterization among microsatellite unstable rectal tumors are necessary.
Asunto(s)
Neutrófilos , Neoplasias del Recto , Humanos , Anciano , Neutrófilos/patología , Terapia Neoadyuvante , Estudios Retrospectivos , Linfocitos/patología , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Pronóstico , Quimioradioterapia AdyuvanteRESUMEN
INTRODUCTION: Primary tumor resection (PTR) in patients with metastatic unresectable colorectal cancer is less and less used to prevent local complications. Although its therapeutic effect is debated, poor data are available about the activity of chemotherapy (CHT) after PTR. The study aims to evaluate trials that compared PTR followed by CHT vs. CHT alone. METHODS: After a literature search on two databases by predefined criteria, studies published from 2011 to 2021 were selected. All studies evaluating the progression-free survival (PFS) of patients receiving CHT after PTR or not were included in a meta-analysis. Finally, 18 possible moderating variables were extracted from each study and examined. RESULTS: Eleven trials reported a reduced risk of progression after first-line CHT among patients receiving PTR (HR 0.72, CI 0.66-0.79). The heterogeneity was moderate (Q = 17.52; p-value = 0.093) and the grade of inconsistence intermediate (I2 = 37.21%). Among moderating variables, female sex and low percentage of patients with liver metastases were related with a stronger effect size of PTR on PFS, whereas a longer OS and a trend to better PFS was evident after poly-chemotherapy regimens. CONCLUSION: PTR could improve the results of first-line CHT in patients with unresectable colorectal cancer with low tumor burden only in the subgroup receiving more aggressive chemotherapy.
Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Cuidados Paliativos/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Neutrophil count reduction after chemotherapy has been related with longer survival of patients with metastatic pancreatic adenocarcinoma, but there is not a standardized measurement for this phenomenon. METHODS: Some parameters related to the change in neutrophil count between the first and the second cycle of chemotherapy or between the baseline count and the nadir have been evaluated among patients with advanced pancreatic cancer at a single institution. A Cox regression model was built which included, in addition to the common prognostic variables, some variables related to the change of the neutrophil count after chemotherapy. RESULTS: One hundred patients were selected. Two neutrophil kinetics related variables predicted overall survival independently, such as the neutrophil count growth rate (hazard ratio [HR] = 1.245; confidence intervals [CIs], 1.077-1.440) and the chemotherapy-induced neutropenia after one cycle (HR = 0.499; CIs, 0.269-0.927). CONCLUSION: The kinetics of neutrophil count after chemotherapy is an early and independent prognostic factor, which appears to be simple to measure at the start of the second cycle of chemotherapy by means of the neutrophil count growth rate.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neutrófilos/metabolismo , Neoplasias Pancreáticas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pancreáticas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Carcinoembryonic antigen (CEA) best reduction after chemotherapy in patients with metastatic colorectal cancer (mCRC) has been reported as a prognostic factor. The study aims to evaluate whether serum CEA kinetics after 8 weeks of chemotherapy was prognostic in patients with mCRC. PATIENTS AND METHODS: A retrospective analysis of patients with mCRC, who received chemotherapy and for whom CEA determinations were available at baseline and after 8 weeks, was performed. A Cox model was built including all variables with a significant correlation with overall survival (OS) after bivariate analysis. RESULTS: Of 200 screened patients with mCRC, 83 were eligible and were enrolled for the analysis. Eighteen variables were tested in bivariate analysis with OS, and a Cox model was built up with 7 of them. Two of 5 CEA kinetics-related variables reported an independent effect on OS when included in the previous Cox model: the CEA response rate after 8 weeks (hazard ratio, 2.02; 95% confidence interval, 1.13-3.59) and the CEA-specific growth rate after 8 weeks (hazard ratio, 1.86; 95% confidence interval, 1.03-3.37). CONCLUSIONS: After 8 weeks from the beginning of chemotherapy, CEA reduction rate of 50% and CEA-specific growth lower than -0.5%/day are effective prognostic factors among patients with high serum CEA levels and could become useful intermediate endpoints of clinical trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/mortalidad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Análisis de SupervivenciaRESUMEN
The primary tumor site of pancreatic cancer has been suggested as a recommended variable in future studies of treatments of patients with unresectable or metastatic pancreatic adenocarcinoma (mPDAC). The aim of the current study is to analyze the differences between mPDAC of the head and mPDAC of the body-tail, both in prognostic and predictive terms in patients with mPDAC receiving palliative chemotherapy. Data of patients with a diagnosis of mPDAC and receiving chemotherapy (CHT), registered in the database of the division of Medical Oncology of the Ospedale Civile di Sanremo, were analyzed. Thirty-two variables were extracted, and their relationship with primary tumor site and outcome were analyzed. One hundred twenty-nine patients were eligible. The characteristics of patients were different between those with the primary tumor of the pancreatic head or body-tail. After construction of two Cox models, two prognostic factors (the number of CHT lines, the neutrophil reduction after one cycle of CHT) were identified as independent among mPDAC of the head, while only one variables (the number of drugs in the CHT regimen) predicted the outcome of patients with body-tail tumors; after statistical correction for false discovery rate, all the three variables maintained their significant relationship with OS. Despite a similar overall survival among parients with tumors of the head compared to those with tumors of body-tail, a very different disease course was reported, with different prognostic and predictive variables.
Asunto(s)
Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/patología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Neoplasias Pancreáticas/patología , Neoplasias Peritoneales/secundario , Adenocarcinoma/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Clinical data reported a relationship between neutrophil-related variables and poor prognosis in patients with metastatic colorectal cancer (mCRC), but only platelet-to-lymphocyte ratio has been reported as prognostic. PATIENTS AND METHODS: A retrospective analysis of 145 patients with mCRC, who received chemotherapy at the department of Oncology of the Ospedale Civile di Sanremo in 2010 to 2013, was performed, and a Cox model was built. RESULTS: In the model, some variables were independently related with overall survival (OS) (resection of the primary tumor, number of drugs included in the first-line chemotherapy regimen), whereas neutrophil-related ones were not. However, after stratification by tumor location, neutrophil-related variables appeared associated with a poor survival among patients with a left-sided mCRC, and in particular, among those ones with a rectal tumor (hazard ratio, 3.732; 95% confidence interval, 1.575-8.845). CONCLUSION: Neutrophil-related variables predicted outcome in patients with left-sided mCRC only. A high prevalence of consensus molecular subtype 4 CRC in patients with metastatic cancer of the rectum is suggested.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/patología , Linfocitos/patología , Neutrófilos/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Docetaxel is the most active agent for metastatic breast cancer, but the optimal treatment regimen as a single agent has yet to be defined. PATIENTS AND METHODS: Two consecutive monocentric phase II trials of docetaxel in metastatic breast cancer were carried out. In Trial I, 36 patients received docetaxel 35 mg/m2 weekly for 6 weeks every 8 weeks and in Trial II, 29 patients received docetaxel 100 mg/m2 day 1 every 21 days. RESULTS: Patient characteristics were comparable. However, patients with liver involvement comprised 25% of cases in Trial I and 55% in Trial II. The overall response rate on an intention-to-treat basis was 19% vs. 45% in Trial I and II respectively; time to progression was 3.8 vs. 7.5 months respectively, and overall median survival was comparable in each trial. CONCLUSION: Docetaxel given at 100 mg/m2 every three weeks appears to be a safe, effective regimen that can be applied in common clinical practice for the treatment of metastatic breast cancer.
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Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Taxoides/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Docetaxel , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Adulto JovenRESUMEN
Inflammation is known to play an important role in the biology of metastatic pancreatic adenocarcinoma (mPDAC), and systemic inflammatory response (SIR) is reported to be closely related to outcome in mPDAC. The aim of the present paper is to assess the prognostic performance of SIR-related variables in patients with mPDAC receiving cytotoxic chemotherapy. Data of patients with mPDAC, who were registered in the database of the division of Medical Oncology of the G. Borea Hospital in Sanremo, were retrospectively collected. Three SIR-related variables were calculated. Univariate and multivariate analyses have been performed by Cox regression, and every SIR-related variable was added to the Cox model. After univariate analyses, four variables reported a significant relationship with overall survival (OS) and were included in a Cox model. Two of the three SIR-related variables were related with OS in the bivariate analyses, and maintained their independent prognostic effect when added to the previous Cox model in multivariate analysis. These variables were two scores, such as neutrophil-platelet score (NPS; HR 2.144, CIs 1.392-3.300) and tri-linear peripheric blood cell score (TRIS; HR 1.813, CIs 1.331-2.468). It appears that the second-generation inflammation-related variables are more effective in predicting prognosis of patients with mPDAC receiving chemotherapy.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/análisis , Mediadores de Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Anciano , Anciano de 80 o más Años , Plaquetas/patología , Femenino , Estudios de Seguimiento , Humanos , Inflamación/metabolismo , Inflamación/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVES: The role of the tumor growth fraction has been investigated poorly in metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to assess whether some prostate-specific antigen (PSA)-related variables of tumor cell kinetics predict the overall survival in early and late mCRPC, and to explore changes in the tumor growth fraction after chemotherapy. METHODS: A retrospective analysis of 3 tumor cell kinetic variables in patients with mCRPC receiving first-line chemotherapy has been performed. The PSA-related tumor growth rate, the log ratio, and the tumor response have been measured at 3 different times. A further analysis has been performed after stratification by the Gleason score and chemotherapy. Finally, tumor growth after progression to chemotherapy has been explored. RESULTS: G at castration resistance is significantly associated with survival after chemotherapy among patients with a low Gleason score (r=-0.650, P-value=0.022). At the time of first-line chemotherapy, both G and PSA response rates report a significant relationship with survival. At the time of postchemotherapy progression, only the G after 12 weeks of chemotherapy maintains a relationship with survival in patients with a low Gleason score (r=-0.483, P-value=0.023); in particular, a tumor growth rate <-0.5%/day appears to be associated with a poor postprogression survival. Despite the lack of correlation between postprogression G and postprogression survival, the response to chemotherapy defines 2 groups with different growth characteristics. CONCLUSIONS: Among patients with mCRPC, tumor cell kinetics appears to be able to predict the outcome, especially in tumors with a low Gleason score.
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Antineoplásicos/uso terapéutico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/patología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Humanos , Cinética , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Estudios RetrospectivosRESUMEN
BACKGROUND: Gemcitabine-based combinations in advanced pancreatic cancer have been reported to have superior activity compared with gemcitabine alone. The results of the commonly used endpoints of clinical trials after chemotherapy or targeted therapy have been poorly reported. METHODS AND MATERIALS: We performed a search of randomized trials of systemic treatment that included gemcitabine plus chemotherapy or targeted therapy versus gemcitabine alone. For selected trials, the differences between the treatment arms for every endpoint were calculated, and a correlation analysis between these differences and the differences in overall survival was performed for every intermediate endpoint. Whenever a correlation coefficient was significant, regression analysis was performed. Finally, an analysis was performed to evaluate the factors that could mediate and moderate the effect of progression-free survival on overall survival. RESULTS: In addition to overall survival, progression-free survival, the overall response rate, and the disease control rate were the most frequently reported endpoints. Of the possible surrogate endpoints of overall survival, progression-free survival appears to be a reliable endpoint to assess chemotherapy (R(2) = 0.646) and chemotherapy plus targeted therapy (R(2) = 0.530) regimens and the disease control rate to assess chemotherapy (R(2) = 0.569). Of the factors that could limit the effect of progression-free survival on overall survival, the interval of radiologic evaluation could play a role. CONCLUSION: In the selected trials, progression-free survival and the disease control rate were the most reliable surrogate endpoints of overall survival. Similar to the time-to-event endpoints, a standardization of response-related endpoints is strongly recommended.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Desoxicitidina/administración & dosificación , Supervivencia sin Enfermedad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , GemcitabinaRESUMEN
The absolute value of carbohydrate antigen 19-9 (CA19-9) pretreatment and its reduction after chemotherapy are established prognostic variables for patients with advanced pancreatic cancer. The present study is a retrospective monoinstitutional evaluation of the prognostic role of the CA19-9 reduction and some CA19-9-related tumor kinetics parameters, such as tumor growth rate constant (G), kinetic tumor response and log ratio. Forty-one cases met the selection criteria. After 8 weeks only G reported an inverse relationship with OS (r = -0.494) that was confirmed by regression analysis (R (2) = 0.192). G after 8 weeks of chemotherapy appears as a possible surrogate end point of overall survival.
Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/sangre , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Estudios RetrospectivosRESUMEN
Although the overall cure rates for cancer in Italy are comparable to those of other developed countries, these results are the product of very heterogeneous facilities. In order to assess the possible impact of improved acute cancer care services on the last phase of life, a retrospective study was carried out which included 4238 patients registered at the Division of Medical Oncology of Imperia Province from January 1995 to December 2002. In 1998 the Province of Imperia, with a population of 217,000, had only two doctors and five day-hospital beds. During 1999 and 2000, resources increased to include five oncology specialists and 10 day-hospital beds. Compared to 1998, in 2002 the number of new patients registering at the Division of Medical Oncology and the number of day-hospital treatments increased by 76% and 67%, respectively. Since end-of-life care for advanced cancer patients is expensive, the length of hospitalization of cancer patients dying in acute hospital settings was analyzed for the years 1995-2002. Of the 4238 patients registered during the eight-year period, 1433 (33.8%) died before 31 December 2002. Among these 1433 patients, the records relative to hospitalization and death were available for 571 cancer patients, 324 males (56.7%) and 247 females (43.3%) with a median age of 70 years (range, 21-91). The average number of days of hospitalization declined from 14.6 (range, 1-76) in 1998 to 8.2 (range, 1-29) in 2002, a decrease of approximately 44%. The length of hospitalization prior to death has declined considerably for cancer patients in the Imperia Province and the costs of acute hospital facilities for end-of-life care in cancer patients have decreased. In addition, fewer days in hospital before death may have had an important impact on the quality of life of these cancer patients.