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BACKGROUND: Incidence of gastric cancer (GC) shows different distribution in Italy, with higher incidence in the north and center. We retrospectively analyzed the clinical data of patients resected at the Hospital of Cremona between January 2007 and December 2016. Available clinical variables were linked with survival to identify possible prognostic factors. MATERIALS AND METHODS: Variables analyzed were age, sex, type of surgery, site, histology, invasion, nodal status, resection margins, grade, HER2 status, Helicobacter pylori infection (neo)adjuvant chemotherapy, adjuvant chemoradiotherapy, neutrophil-to-lymphocyte ratio, number of nodes removed and type of lymphadenectomy. Overall survival (OS) was estimated by the Kaplan-Meier method and differences between groups by the log-rank test. Data on OS were analyzed by Cox regression and the final model was obtained using the step-wise method. RESULTS: 379 patients were considered, out of which 195 were operated from 2007 to 2011 and 184 from 2012 to 2016. Median follow-up was 25.5 months, median OS 31.3 months and time to recurrence 23.2 months. D2 resection rate increased from 36% (period 2007-2011) to 74% in 2012-2016 (p = 0.01) with a higher mean number of nodes collected (20.98 for 2007-2011 and 23.53 for 2012-2016, p = 0.040). Only 37% of patients received a postoperative treatment. At multivariate analysis, variables associated with OS were age (p = 0.002), stage (p < 0.001), resection margins status (p < 0.001), adjuvant chemotherapy (p < 0.010) and tumor location (cardia vs non-cardia) (p = 0.029). CONCLUSIONS: Our analysis shows that completeness of resection and lower stage are strong predictors of long-term survival in GC, providing the rationale for adjuvant and neoadjuvant approaches (chemotherapy, radiotherapy or combined). Cardial GC has worse prognosis compared to distal cancers. TRIAL REGISTRATION NUMBER: Service evaluation number 256, protocol 16821/17, date 05 June 2017.
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Adenocarcinoma/cirugía , Quimioradioterapia Adyuvante , Gastrectomía/métodos , Terapia Neoadyuvante , Neoplasias Gástricas/cirugía , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Amplificación de Genes , Infecciones por Helicobacter , Humanos , Italia , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/genética , Estudios Retrospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: The gastric cancer incidence rate differs widely across geographical areas. In Italy, in the province of Cremona the incidence is high, compared to the national situation. For this reason a specialized population-based registry was set up. METHODS: The collection encompasses all gastric cancers diagnosed in the three districts of the province since January 1, 2010. The main data sources were the pathological and Hospital Discharge Records and patient clinical charts. Only diagnoses of primary gastric cancer were considered. For each case the following variables were registered: personal data, medical history and symptoms at diagnosis; imaging assessments performed, details on surgery and other treatments received; genetic background and biomolecular characteristics; social and environmental factors. RESULTS: As of November 2017, 1087 cases were collected; of which 876, diagnosed up to December 2015, were analyzed. Male/female ratio was 1.4. The European Age-standardized Incidence Rate was 41.4 for males and 28.3 for females as compared to a national average of 33.3 and 17.0 respectively. Median age at diagnosis was 73 for male and 78 for female. Helicobacter Pylori infection was present in fewer than 20% of cases. HER-2 gene was amplified in about 25% of cases. Primary tumour location was the gastro-esophageal junction or cardia in 17.5% in males and 8.3% in females. The majority of cases (58.3%) were diagnosed at an advanced stage and overall only 41.2% underwent surgery. Median overall survival was 14.8 months for men and 18.5 for women. Age standardized 5-year relative survival was 31.4% for men and 40.5% for females. Neoadjuvant treatment was performed in fewer than 10% of patients who underwent surgery, and the rate of postoperative therapy adherence was low. DISCUSSION: This study shows a high gastric cancer incidence in the province of Cremona, with a geographical spread across different districts. Moreover, a high percentage of gastric cancers were detected at an advanced stage of disease and a low rate of 5-year relative survival was registered. Based on these findings, effective preventive interventional health strategies and screening procedures need to be implemented to reduce the impact of this pathology in this geographical area.
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Neoplasias Gástricas/epidemiología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Femenino , Humanos , Incidencia , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Evaluación del Resultado de la Atención al Paciente , Vigilancia de la Población , Pronóstico , Sistema de Registros , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiología , Neoplasias Gástricas/mortalidad , Evaluación de SíntomasRESUMEN
INTRODUCTION: Major pathologic regression after neoadjuvant therapy is a strong and favorable prognostic factor in several types of cancer (breast, rectal and bladder). This information is less clear and has yet to be systematically evaluated in upper gastrointestinal tumors. We performed a meta-analysis to evaluate the prognostic impact of tumor regression after preoperative therapy on disease-free survival (DFS) and overall survival (OS) in gastro-esophageal cancer patients. METHODS: we searched for relevant articles in PubMed, SCOPUS, Web of Science, CINAHL, LILACS, Ovid, Cochrane Library, Google Scholar and Embase up to June 2, 2016. Data of tumor regression (complete or near-complete pathologic response) that independently correlated with OS and DFS in multivariate analysis were extracted, and the proper hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were pooled according to the random effect model. RESULTS: a total of 17 studies-which included 3145 patients-were considered in the final analysis. Major pathologic response was significantly related with better OS (HR 0.46, 95% CI 0.32-0.66, P < 0.001) and DFS (HR = 0.40, 95% CI 0.26-0.62, P < 0.001). Pathologic complete response (pCR) or major tumor regression were associated with the same degree of benefit in outcome compared to no or minimal pathologic regression, regardless of histology. CONCLUSION: major pathologic response is associated with a significant improvement in OS compared to no response or minor pathologic changes after neoadjuvant therapy in gastro-esophageal cancers. This should be considered a robust prognostic factor to guide postoperative treatment and follow-up.
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Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Terapia Neoadyuvante , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Esofagectomía , Gastrectomía , Humanos , Estadificación de Neoplasias , Tasa de SupervivenciaRESUMEN
The aim of this study was to explore the efficacy and toxicities of a combined regimen of bevacizumab plus immunotherapy and chemotherapy (BIC) and the circulating T regulatory cells (Treg) in metastatic renal cell cancer (mRCC). Nephrectomized mRCC patients were enrolled into a multicenter single-arm dose-finding study with five escalated dose levels of chemotherapy with intravenous gemcitabine and 5-fluorouracil associated with fixed intravenous doses of bevacizumab, subcutaneous low doses of interleukin-2, and interferon-α-2a. An expanded cohort (phase II study) was treated at the recommended dose for additional safety and efficacy information according to minimax Simon two-stage design. Blood samples for Treg were collected and evaluated by fluorescence-activated cell sorting (FACS) analysis on cycle 1. Fifty-one patients were entered to receive one of five dose levels. Median age was 58 years (male 67 %, pretreated 49 %): 15 patients were low risk according to Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, while 27 and nine were respectively intermediate- and high-risk patients. More frequent grade 3 and 4 toxicities included nonfebrile neutropenia, thrombocytopenia, and fever. Among patients evaluable for response (49), 29.5 % had partial response and 37 % stable disease. Overall median time to progression and median overall survival were 8.8 and 22.67 months, respectively. We observed a rapid increase in the percentage of Treg after immunotherapy and a reduction after bevacizumab only in patient who obtained a partial response or stable disease. The BIC was feasible, well tolerated, and shown interesting activity. Further studies are needed to explore if Treg could have a role in clinical response in mRCC treated with bevacizumab.
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Inhibidores de la Angiogénesis/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Inmunoterapia/métodos , Neoplasias Renales/tratamiento farmacológico , Linfocitos T Reguladores/efectos de los fármacos , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Separación Celular/métodos , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Fluorouracilo/administración & dosificación , Humanos , Inmunoterapia/efectos adversos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interleucina-2/administración & dosificación , Italia , Estimación de Kaplan-Meier , Neoplasias Renales/inmunología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Nefrectomía , Proteínas Recombinantes/administración & dosificación , Linfocitos T Reguladores/inmunología , Factores de Tiempo , Resultado del Tratamiento , GemcitabinaRESUMEN
There is conflicting evidence on the predictive role of KRAS status when cetuximab is added to oxaliplatin-based regimens. This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients enrolled in TEGAFOX-E (cetuximab, oxaliplatin and oral uracil/ftorafur--UFT) phase II study. Twenty-eight patients were enrolled and all were evaluable for safety and activity. Twenty-three specimens were analysed for KRAS, BRAF, NRAS, PI3KCA and TP53 mutational status by means of polymerase chain reaction and correlated with objective response, progression-free survival and overall survival. An evident increase of response rate was noted in KRAS/NRAS wild-type cases (70 versus 33%, P = 0.198). KRAS/NRAS wild-type status showed an independent association with a longer progression-free survival (44 versus 9 weeks, P = 0.009). Considering the combined assessment of BRAF, KRAS/NRAS and TP53, a trend towards an increase of response rate was noted in patients without mutations (83 versus 33%, P = 0.063). Moreover, patients with all wild-type genes had significantly longer progression-free survival than patients with any mutation (48 versus 10 weeks, P = 0.007). As a single biomarker, only KRAS/NRAS proteins maintained an independent value for outcome prediction. Patients with KRAS/NRAS, BRAF and TP53 wild-type tumours could derive the maximal benefits from treatment with cetuximab, oxaliplatin and UFT.
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Adenocarcinoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Resistencia a Antineoplásicos/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cetuximab , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Femenino , GTP Fosfohidrolasas/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Proteínas de la Membrana/genética , Mutación , Proteínas Nucleares/genética , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tegafur/administración & dosificación , Factores de Transcripción/genética , Proteína p53 Supresora de Tumor/genética , Uracilo/administración & dosificación , Proteínas ras/genéticaRESUMEN
Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.
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Antineoplásicos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Adhesión a Directriz , Humanos , Italia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neutrófilos/citología , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Therapeutic approach for patients with metastatic breast cancer (MBC) is still controversial. This study was conducted to assess the efficacy and safety of bevacizumab in combination with docetaxel plus capecitabine as first-line treatment for MBC. The feasibility of bevacizumab maintenance therapy in this setting was also evaluated. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients received bevacizumab 15 mg/kg and docetaxel 60 mg/m(2) on day 1, plus capecitabine 900 mg/m(2) twice daily on days 1-14 every 21 days. Treatment was administered for up to 6 cycles, then bevacizumab continued until progressive disease. The primary end point was progression-free survival (PFS); secondary end points were tumor response rate, overall survival, and toxicity. RESULTS: Seventy-nine eligible patients were treated with bevacizumab in combination with docetaxel plus capecitabine. The overall response rate was 61 %, with a complete response rate of 8 % and a median duration of response of 10 months. At a median follow-up of 28 months, the median PFS was 11 months. Fifty-two (65 %) patients received bevacizumab maintenance therapy for a median duration of 7 months (range 1 to 33+). Neutropenia was the most common grade 3-4 toxicity (28.1 % of patients), and two fatal adverse events occurred (septic shock and gastrointestinal perforation). CONCLUSIONS: Bevacizumab in combination with docetaxel and capecitabine demonstrates significant activity and quite acceptable toxicity profile as first-line treatment of MBC. Subsequent maintenance therapy with bevacizumab is feasible for a long period of stable disease. Results deserve confirmation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Cooperación del Paciente , Taxoides/administración & dosificaciónRESUMEN
OBJECTIVES: The aim of this study was to describe the patterns of breast cancer relapse and the factors influencing therapeutic choices in an unselected postmenopausal population. METHODS: Five hundred and thirty-nine patients were enrolled between October 1999 and March 2001. The majority (92.6%) underwent surgery for the primary tumor: there was no difference between general and university hospitals in terms of the type of mastectomy, but a slight difference was found between Southern and Northern Centers. RESULTS: At the time of first relapse, 61.6% of the patients had a good Karnofsky performance status. The median disease-free interval (DFI) was 34 months. More than half of the patients (62.3%) presented a single metastasis. Metastatic disease was treated with chemotherapy in 64.8% of cases (alone in 44.1%, and in combination with hormone therapy in 20.1%), hormone therapy alone was given in 30.8% of cases. The main reasons for choosing chemotherapy were age (31%), standard guidelines (19.4%) and the site of metastatic disease (14.3%), and those for selecting hormone therapy were age (26.6%), site of relapse (19.3%), standard guidelines (19.2%), biological tumor characteristics (14.3%) and the DFI (11.1%). Taxane-containing treatments accounted for 46.1% of the chemotherapies, whereas letrozole was the preferred hormone (41.2%). CONCLUSION: The first relapse of breast cancer is often single, at bone or viscera, and mainly diagnosed by instrumental screening examinations. The preferred chemo- and hormone therapies are taxane-containing regimens and letrozole, respectively.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Recurrencia Local de Neoplasia/terapia , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Escolaridad , Empleo , Femenino , Humanos , Italia/epidemiología , Estado Civil , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Radioterapia Adyuvante , Taxoides/uso terapéuticoRESUMEN
This study aimed to verify whether the advantage in terms of response rate and survival of dacarbazine plus tamoxifen over dacarbazine alone in metastatic malignant melanoma reported in a previous randomized trial was due to a specific interaction of dacarbazine with tamoxifen. A total of 125 patients with locoregional or disseminated malignant melanoma were randomized to receive dacarbazine (250 mg/m(2) days 1-5 every 3 weeks) plus tamoxifen (arm A) or vindesine (3 mg/m(2) every week for 6 weeks, then every 2 weeks) plus tamoxifen (arm B). Of the 125 randomized patients, 57 and 59 were evaluable in arm A and B, respectively. The complete response rates were the same (2% versus 2%) and the complete plus partial response rates were similar (11% versus 14%) in the two groups. There was no significant difference in survival. Neither response or survival correlated with gender. In conclusion, when combined with tamoxifen, dacarbazine does not have a specific effect on response or survival compared with vindesine. The lower response rate to dacarbazine plus tamoxifen (11%) than that reported in the previous trial (28%) might be explained by actual differences in patient and/or participating centre accrual characteristics in the presence of apparently identical eligibility criteria.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dacarbazina/administración & dosificación , Femenino , Humanos , Masculino , Melanoma/mortalidad , Melanoma/secundario , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Tasa de Supervivencia , Tamoxifeno/administración & dosificación , Resultado del Tratamiento , Vindesina/administración & dosificaciónRESUMEN
We compared a relatively short regimen of monochemotherapy with epirubicin versus polychemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as adjuvant treatment for stage I and II breast cancer patients. 348 patients with oestrogen receptor negative (ER-) node negative and ER- or ER+ node-positive with <10 nodes were accrued. CMF was given intravenously (i.v.) on days 1 and 8, every 4 weeks, for six courses; epirubicin was given weekly for 4 months. Postmenopausal patients received tamoxifen for 3 years. The primary endpoints were overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS). Outcome evaluation was performed both in eligible patients and in all randomised patients according to the intention-to-treat principle. 8 randomised patients were considered ineligible. At a median follow-up of 8 years, there was no difference in OS (Hazard Ratio (HR)=1.11, 95% Confidence Interval (CI): 0.77-1.61, P=0.58), EFS (HR=1.14, 95% CI: 0.78-1.64, P=0.48), and RFS (HR=1.14, 95% CI: 0.8-1.64, P=0.48) between the two arms for all of the patients. At 8 years, the RFS percentages (+/-Standard Error (S.E.)) were 65.4% (+/-4%) in the CMF arm and 62.7% (+/-4%) in the epirubicin arm; for EFS these were 64.2% (+/-4%) for CMF and 60.8% (+/-4%) for epirubicin, respectively. A significant difference in RFS (P=0.015) was observed in patients with 4-9 positive nodes in favour of the CMF arm. Toxicity in the two arms was superimposable except for more frequent grade 3 alopecia in the epirubicin-treated patients (P=0.001). Overall, at a median follow-up of 8 years, there were no differences between the two arms in terms of OS, EFS and RFS.
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Antibióticos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Epirrubicina/administración & dosificación , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Epirrubicina/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Humanos , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: The objective of this study was to evaluate response, toxicity, and immunologic effects of an original immunotherapy schedule based on repeated cycles of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFNalpha) in patients with metastatic renal cell carcinoma (mRCC). METHODS: Fifty patients who underwent nephrectomy received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFNalpha twice weekly for 4 consecutive weeks. The cycle was regularly repeated indefinitely at 4-month intervals in all patients, irrespective of their response. rIL-2 (1 x 10(6) IU/m(2)) was administered every 12 hours on Days 1 and 2 and once per day on Days 3-5 of each week; rIFNalpha (1.8 x 10(6) IU/m(2)) was given on Days 3 and 5. Toxicity was graded according to the World Health Organization (WHO) criteria. Forty percent of the patients had only one metastatic disease site at the time of treatment. The Kaplan-Meier method was used to estimate survival, and an analysis of variance was used to evaluate the effects on leukocytes and lymphocyte subsets over time. RESULTS: A total of 241 cycles were administered. One patient achieved a complete response, and five patients achieved a partial response. Five patients had stable disease, and 30 patients had progressive disease. Nine patients were not evaluable for response. The overall response rate was 12% (95% confidence interval, 3-21%) on the basis of an intent-to-treat analysis. The 36-month survival probability for all 50 patients was 47%. Treatment-related toxicity was limited to WHO Grades 1 and 2. Both lymphocyte and eosinophil levels significantly increased after all cycles (by 42% and 353%, respectively). The treatment also induced significant increases in the CD25 positive (24%), CD56 positive (28%), and CD3 negative/CD56 positive (54%) lymphocyte subsets. CONCLUSIONS: Long-term, repeated treatment with low doses of rIL-2 and rIFNalpha is feasible in patients with mRCC. The schedule induces clinical response rates and survival probabilities are similar to those obtained using higher doses.
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Antineoplásicos/farmacología , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/inmunología , Interferón-alfa/farmacología , Interleucina-2/farmacología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/inmunología , Anciano , Antineoplásicos/administración & dosificación , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Inmunoterapia , Inyecciones Intramusculares , Inyecciones Subcutáneas , Interferón-alfa/administración & dosificación , Interleucina-2/administración & dosificación , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
In a retrospective analysis of a series of clinical trials by Levin and Hryniuk in 1987, the average relative dose intensity of first-line chemotherapy for advanced ovarian cancer correlated significantly with clinical response and survival, and cisplatin was the only drug for which the outcome correlated with the individual drug relative dose intensity. There was a need to test whether and to what extent this evidence would be confirmed in a prospective evaluation. In this study 101 patients with advanced ovarian carcinoma were randomized to receive the same total dose of cisplatin but at the conventional 3-weekly schedule (CTWS) (100 mg/m2 every 3 weeks for six cycles) (51 patients) or at an experimental accelerated weekly schedule (AWS) (100 mg/m2 every week for two triplets of three cycles separated by a 5-week interval) (50 patients). To benefit from a multidrug regimen at the same extent, patients in both arms sequentially received four cycles of doxorubicin and cyclophosphamide. The median follow-up period of this study is 9.7 years. In 42 and 40 patients of the two arms having evaluable response, the clinical complete response rates to cisplatin were 14% and 22% and the complete plus partial response rates were 48% and 55% in the CTWS and in the AWS arm, respectively. These differences were not statistically significant. However, the survival curves were similar during the first 2 years but clearly diverged thereafter in favor of the AWS arm (p = 0.07). At 5 years, 12% and 30% of the patients were still alive in the CTWS and in the AWS arm, respectively. Hematologic toxicity was not relevant in either arm of the study. Nonhematologic toxicity, especially ototoxicity, was substantial and significantly higher in the AWS arm. Although statistically nonsignificant, this AWS regimen of cisplatin is associated with long-term better survival compared to the CTWS regimen in advanced ovarian carcinoma. This accelerated approach administering cisplatin should be further investigated, especially in patients with low residual disease after primary surgery.
Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma/tratamiento farmacológico , Cisplatino/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/cirugía , Quimioterapia Adyuvante , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias Ováricas/cirugía , Estudios Prospectivos , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
We designed three new four-drug cisplatin-containing combinations and evaluated their activity in a randomized phase II study including patients with locally advanced (stage III) and locally recurrent breast carcinoma. All combinations included methotrexate (M) on day 1 and cisplatin (P) on day 2 (MVAC-like combinations) and differed from one another by the addition of Epirubicin (Epi), Vincristine (V), Etoposide (E), Mitomycin (Mi). Based on the administered agents, they were named MPEMi, MPEpiE, MPEpiV. The combinations were randomly assigned to 101 patients, 57 with locally advanced and 44 with locally recurrent breast carcinoma. Response was evaluated after 4 cycles. The complete response (CR) rates were 7% and 43% and the CR plus partial response (PR) rates were 84% and 89% in locally advanced and in locally recurrent disease, respectively. In locally advanced disease, a pathologic CR (pCR) was assessed in seven of 57 patients (12%). There were no significant differences among the three combinations. The toxicities were at times severe, but generally tolerable, as demonstrated by the high cumulative doses of the drugs received by the patients. In conclusion, these three innovative chemotherapy regimens induced high CR plus PR rates in the neoadjuvant treatment of stage III and of locally recurrent breast carcinoma, and a high rate of pCR in stage III disease. These regimens warrant testing in phase III trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Cisplatino/administración & dosificación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Leucovorina/administración & dosificación , Metotrexato/administración & dosificación , Persona de Mediana Edad , Mitomicina/administración & dosificación , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: An emotional campaign promoting the Di Bella cancer therapy was launched by the Italian media in 1997. Its effects on patients' hopes, feelings, and decision-making processes were largely unknown. We undertook an investigation of this issue. METHODS: Between Feb 25 and March 31, 1998, a ten-item questionnaire was distributed to 1300 unselected adult patients attending 13 cancer centres throughout Italy. Four expert psycho-oncologists reviewed the design and validity of the contents of the questionnaire. Sociodemographic information was also collected. FINDINGS: 1120 (86%) questionnaires were returned and analysed. The main sources of information were television/radio (62%) and newspapers (26%); only 5% cited doctors. The campaign induced optimism in the patients about the efficacy of the method (ineffective 1%, effective 42%, uncertain 57%), and 53% said their hope of cure was increased. However, 48% felt more confused. 24% do not discuss new treatments with their oncologists, and 20% would like to but cannot. When choosing a treatment, the advice of a trusted doctor was judged more important than scientific progress (53% vs 32%) and 63% would try even unproven treatments in the hope of a cure. Replies to many of the questions were influenced by patients' educational attainment and by the degree of communication with their oncologists. INTERPRETATION: Science cannot prevent the harm caused by such campaigns and their psychological consequences, particularly for less educated patients. When making decisions, patients are looking for hope from the treatment and trust in their doctor, both of which depend on effective doctor-patient communications that therefore need to be improved.
Asunto(s)
Terapias Complementarias , Medios de Comunicación de Masas , Neoplasias/tratamiento farmacológico , Neoplasias/psicología , Pacientes/psicología , Ensayos Clínicos Fase II como Asunto , Combinación de Medicamentos , Escolaridad , Ética Profesional , Femenino , Humanos , Italia , Masculino , Relaciones Médico-Paciente , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
Patients with histologically confirmed advanced colorectal cancer were randomized to receive folinic acid (FA; 500 mg/mq in 2-hour intravenous infusion) and 5-fluorouracil (5FU; 600 mg/mq given as an intravenous bolus 1 hour after FA), beginning every week for 6 weeks, followed by a 2-week rest period, either without hydroxyurea (HU, arm A) or with HU (35 mg/kg per day) given orally in three administrations (every 8 hours) starting 6 hours after 5FU administration (arm B). Six weekly doses were considered one course. One hundred eighty-two patients were randomized in this trial and 162 (89%) were evaluable for response: 81 patients in arm A and 81 patients in arm B. Objective response was observed in 18 (one complete response and 17 partial responses) of 81 evaluable patients (22%; 95% confidence interval, 13-31%) in arm A, and 24 (nine complete responses and 15 partial responses) of 81 patients (30%; 95% confidence interval, 20-40%) in arm B. There was no difference in terms of median time to progression and median survival. Gastrointestinal toxicity was the most frequently observed toxicity in both arms. The double modulation of 5FU, FA plus HU does not appear to be better than the classic 5FU plus FA schedule. This trial confirms that 5FU and FA reached a plateau of 20% to 30%.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Neoplasias Colorrectales/patología , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Hidroxiurea/administración & dosificación , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
En nuestra realidad clínica los pacientes sometidos a cirugía cardíaca permanecen en ventilación mecánica alrededor de 14 horas, siendo un objetivo primordial la extubación precoz para evitar complicaciones y disminuir costos. Dentro de este contexto, estudiamos el comportamiento de factores predictores de la extubación precoz en 230 pacientes adultos sometidos a cirugía cardíaca entre septiembre de 1994 y abril de 1995 en la Unidad de Recuperación de Cirugía Cardiovascular del Hospital Clínico de la Pontíficia Universidad Católica de Chile. Además de considerar parámetros clásicos de desconexión tales como intercambio gaseoso, estado hemodinámico, nivel de conciencia y patrón respiratorio espontáneo, evaluamos, durante la ventilación mecanica, la distensibilidad estática (Cs) y las distensibilidad dinámica (Cd). Posterior a conexión a tubo Tpor 30 minutos, evaluamos: volumen corriente (Vt),frecuencía respíratoria (FR). Volumen minuto (VE) e índice de respiración superficial. Se consideró extubacíón precoz o (+) a aquella extubación exitosa en las primeras 24 horas del postoperatorio y extubación (-) a quienes permanecieron en VM durante más de 24 horas o requirieron reintubación y conexión a ventilación mecánica. De acuerdo a los resultados, los factores predictores evaluados no permiten predecir significativamente cual es el momento más adecuado para la desconexión precoz de ventilación mecánica en ésta población de pacientes. Sin embargo, los factores que sí presentaron una diferencia estadísticamente significativa entre los pacientes con extubación (+) vls los con extubación (-), fueron algunos factores clínicos como la capacidad funcional, el riesgo operatorio, el tipo y tiempo de cirugía, el tiempo de permanencia en circulación extracorpórea, el uso de drogas vasoactivas y las complicaciones postoperatorias
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Respiración Artificial/métodos , Cirugía Torácica , Desconexión del Ventilador , Tiempo de Internación , Periodo Posoperatorio , Mecánica RespiratoriaRESUMEN
PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.
Asunto(s)
Hormona Adrenocorticotrópica/administración & dosificación , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Neoplasias/tratamiento farmacológico , Vómitos/prevención & control , Adulto , Anciano , Antieméticos/uso terapéutico , Preparaciones de Acción Retardada , Dexametasona/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vómitos/inducido químicamenteRESUMEN
Twenty-one nephrectomized patients with metastatic renal cell cancer were treated with recombinant interleukin 2 (rlL-2) and interferon alpha (rIFN alpha). rIL-2 was administered s.c. at a dose of 1 x 10(6) IU m(-2) every 12 h on days 1 and 2, followed by 0.5 x 10(6) IU twice daily on days 3-5; rIFN alpha-2 was given i.m. as 1.8 x 10(6) IU m(-2) on days 3 and 5 of each week for 4 consecutive weeks. The cycle was regularly repeated at 4-month intervals and continued ad libitum in patients showing some response and in patients with progressing disease. Of 20 patients evaluable for treatment response, one (5%) had a complete response and three (15%) showed partial response. Three patients (15%) achieved stable disease and 13 (65%) were evaluated as having progressive disease. The estimated actuarial 44-month survival rate was 44%. Toxicity was limited to WHO grades 1 and 2 only.
Asunto(s)
Carcinoma de Células Renales/terapia , Interferón Tipo I/administración & dosificación , Interleucina-2/administración & dosificación , Neoplasias Renales/terapia , Adulto , Anciano , Femenino , Humanos , Interferón Tipo I/efectos adversos , Interleucina-2/efectos adversos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificaciónRESUMEN
The Authors report the results with combination of cisplatin, methotrexate, vinblastine with adriamycin or epidoxorubicin (MVAC v MVEEC), in the neoadjuvant treatment of muscle-infiltrating bladder cancer (T2-4NO-1MO), before cystectomy. MVAC has been used in 29 patients and MVEEC in 25, who met eligibility criteria. Results from this prospective randomised trial show that MVAC and MVEEC can produce clinical and pathologic down-staging in 40-50% of cases: cCR+cPR are 15/28 (54%), pCR+pPR are 11/25 (44%). The survival duration of "pathologic" responders has been significantly longer than that of no responders (median no achieved at 200 weeks v 124 weeks for "pathologic" no responders). We conclude that neoadjuvant chemotherapy with MVAC or MVEEC select the more responsive patients, who have a longer survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano , Carcinoma de Células Transicionales/cirugía , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Terapia Combinada , Cistectomía , Doxorrubicina/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/cirugía , Vinblastina/uso terapéuticoRESUMEN
BACKGROUND: The M-VAC combination is very effective in bladder carcinoma, as are all four drugs, as single-agent, in advanced breast carcinoma. PATIENTS AND METHODS: M-VAC was given in 27 patients, 4 with locally advanced breast carcinoma, 3 with local recurrence and 20 with distant metastases. The median age was 51 (range 25; 70). Eleven of the 20 patients with metastatic disease has been previously treated with a different chemotherapy. RESULTS: 15 of 26 evaluable patients responded, with 9 (35%) complete remissions and 6 partial responses. The overall response rate (CR plus PR) was 57% (95% confidence interval 38% to 76%). In patients with metastatic disease the median duration of response was 7 months (range 4+; 36+), median time to progression 5 months (range 1; 36+) and median duration of survival 17 months (range 1; 40+). CONCLUSION: The M-VAC combination is very effective in locally advanced, locally recurrent and metastatic breast carcinoma. Further trials are warranted to evaluate whether the activity of this combination is partially schedule-dependent.