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R Porta,
J M Sánchez-Torres,
L Paz-Ares,
B Massutí,
N Reguart,
C Mayo,
P Lianes,
C Queralt, V Guillem,
P Salinas,
S Catot,
D Isla,
A Pradas,
A Gúrpide,
J de Castro,
E Polo,
T Puig,
M Tarón,
R Colomer,
R Rosell
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ABSTRACT: Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.
European Respiratory Journal 03/2011; 37(3):624-31. · 5.89 Impact Factor
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J Bellmunt,
L Paz-Ares,
M Cuello,
F L Cecere,
S Albiol, V Guillem,
E Gallardo,
J Carles,
P Mendez,
J J de la Cruz,
M Taron,
R Rosell,
J Baselga
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ABSTRACT: Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancer patients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival.
Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response.
Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival.
The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.
Annals of Oncology 04/2007; 18(3):522-8. · 6.43 Impact Factor
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J Tabernero,
M A Climent,
A Lluch,
J Albanell,
J B Vermorken,
A Barnadas,
A Antón,
C Laurent,
J I Mayordomo,
N Estaun,
I Losa, V Guillem,
J Garcia-Conde,
J L Tisaire,
J Baselga
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ABSTRACT: A phase II randomised trial was conducted to evaluate the tolerability and activity of weekly or 3-weekly docetaxel in patients with metastatic breast cancer.
Eighty-three patients with histologically proven metastatic breast cancer were randomised to receive either docetaxel 40 mg/m2 weekly for 6 consecutive weeks followed by 2 weeks without treatment (n = 41), or docetaxel 100 mg/m2 on day 1 every 3 weeks (n = 42).
The incidence of all grade 3-4 adverse events was higher in the 3-weekly group than in the weekly group (96 versus 44), and the number of patients with grade 3-4 adverse events was also greater in the 3-weekly group (31 versus 20). Analysis of individual adverse events tended to favour the weekly regimen. Intent-to-treat overall response rate was 34% and 33% in the weekly and 3-weekly groups, respectively. Median time to progression was 5.7 and 5.3 months after weekly and 3-weekly docetaxel, respectively, and median time to treatment failure was 4.1 and 4.9 months, respectively.
Weekly docetaxel is an active regimen in metastatic breast cancer with comparable efficacy to 3 weekly docetaxel. Although both schedules were well tolerated, weekly docetaxel appears to have a more favourable toxicity profile.
Annals of Oncology 10/2004; 15(9):1358-65. · 6.43 Impact Factor
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R Colomer,
A Llombart-Cussac,
A Lluch,
A Barnadas,
B Ojeda,
V Carañana,
Y Fernández,
J García-Conde,
S Alonso,
S Montero,
J Hornedo, V Guillem
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ABSTRACT: We wanted to assess the toxicity and efficacy of paclitaxel plus gemcitabine in advanced breast cancer and to confirm whether circulating HER2 extracellular domain (ECD) correlates with treatment response.
Forty-three patients received paclitaxel 150 mg/m2 followed by gemcitabine 2500 mg/m2, both on day 1 of 14-day cycles, with a maximum of eight cycles. Serum levels of HER2 ECD were assessed by ELISA.
All patients were evaluable for toxicity and 42 for efficacy. Overall toxicity was low. Grade 3 neutropenia occurred in 12% of patients and grade 4 in 17%, and other grade 3 toxicities in <5%. One patient had an allergic infusion reaction. Overall response rate was 71% [95% confidence interval (CI) 62% to 81%], with 11 patients achieving a complete response (26%). With a median follow-up of 26 months, the median time to progression was 16.6 months. Response rate correlated significantly with HER2 ECD, with 42% of HER2 ECD-positive patients responding versus 83% of HER2 ECD-negative patients (P = 0.02). Furthermore, response duration was shorter in patients with positive HER2 ECD levels (7.9 versus 14.4 months; P = 0.04).
Paclitaxel plus gemcitabine given as an every 2-weeks schedule is a well tolerated and active regimen in advanced breast carcinoma. This is an attractive combination to use when anthracyclines are not indicated, such as in HER2 positive cases that receive trastuzumab. In addition, elevated levels of HER2 ECD adversely affect the efficacy of treatment.
Annals of Oncology 02/2004; 15(2):201-6. · 6.43 Impact Factor
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ABSTRACT: El cáncer de mama representa el primer tumor tanto en incidencia como en mortalidad en la mujer occidental, observándose un aumento de su incidencia en nuestro pais en los últimos años. A pesar de ello, la tasa de mortalidad ha mejorado sensiblemente, gracias en gran medida a los programas de screening y a los avances terapéuticos. Sin embargo, a pesar de un diagnostico precoz junto a la aplicación de una terapéutica óptima local, (cirugía conservadora, radioterapia, braquiterapia, etc..) y sistemica (terapia hormonal y/o quimioterapia), más de un 30% de las pacientes presentaran enfermedad diseminada en los primeros 10 años del diagnóstico.Uno de los temas que más debate sigue originando es el de la utilidad de las pruebas complementarias en el seguimiento de las pacientes afectas de un cáncer de mama. Estudios históricos, realizados en la década de los 80, redundaban en la ausencia de eficacia tanto de la gammagrafia ósea como de la ecografía hepática en modificar él pronostico y supervivencia de estas pacientes. Con la introducción en los últimos años de técnicas diagnósticas más sensibles y tratamientos sistémicos de elevada eficacia, sé esta reconsiderando la posibilidad de modificar la historia natural de la enfermedad avanzada a través del diagnostico precoz.La Tomografía por Emisión de Positrones (PET) con 18FDG (18Fluordeoxiglucosa) en el diagnóstico y seguimiento del cáncer de mama, al igual que otras aplicaciones clínicas de la PET, se ha desarrollado de forma vertiginosa en los últimos años, a medida que se ha ido demostrando su eficacia diagnóstica. En el cáncer de mama se ha propuesto su uso en diferentes campos: 1) en el screening o detección del cáncer de mama en mujeres jóvenes con mamas densas (gran componente fibroso) o con implantes protésicos donde la mamografía adolece de una baja especificidad (30%)[10], 2) en la estadificación ganglionar axilar en los tumores mamarios de cuadrantes externos y en los ganglios de la cadena mamaria interna cuando el tumor asienta en cuadrantes internos. La afectación ganglionar en el momento del diagnóstico, es por sí solo, el factor pronóstico más importante. De esta forma, el 72% de las mujeres sin afectación ganglionar siguen vivas a los 5 años, solo el 59% de ellas cuando tienen de 1 a 3 ganglios metastásicos y el 41% cuando tienen más de 3 ganglios, 3) en la estadificación tanto loco-regional como a distancia del cáncer de mama localmente avanzado, contribuyendo a la detección de metástasis a distancia en una única exploración y ayudando a decidir el tratamiento adecuado de cada paciente, 4) en el reestadiaje de recurrencia tumoral del cáncer de mama, ante la elevación de marcadores tumorales (Ca 15.3), por sospecha clínica y/o ante hallazgos radiológicos negativos o no concluyentes y 5) como monitorización de la respuesta a la quimioterapia. Trabajos recientes han valorado el impacto que el resultado de la PET tiene en el manejo terapéutico de los pacientes con cáncer de mama con muy buenas perspectivas.El objetivo de este caso clínico que presentamos es destacar la gran utilidad de la PET en el diagnóstico de recidiva tumoral del cáncer de mama tratado ante el hallazgo radiológico no concluyente y la sospecha clínica de recurrencia de la enfermedad, así como en el seguimiento y valoración de la respuesta a la terapéutica aplicada.
Alasbimn Journal. 01/2004;
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ABSTRACT: Breast cancer represents the must common cancer in incidence as in mortality among western women, it has been reported an increase of its incidence in our country in recent years. In spite of it, reduced mortality is a reflection of early diagnosis due to the programs of screening and more effective treatment. Nevertheless, in spite of an early diagnosis followed by application of a optimal therapy (conservation surgery, radiation therapy, brachiterapy, etc..) and systemic therapy (hormonal therapy and/or chemotherapy), more than one 30% of the patients presented distant metastasis in the first 10 years of evolution.One of the issues that more debates continues originating is the usefulness of the principal imaging modalities in monitoring of patients with breast of cancer. Historic studies, performed in the decade of the 80, called the attention on the absence of efficacy of the bone scintigraphy as of the ultrasonography liver in modifying of prognosis and survival of these patients. With the introduction in recent years of more sensitive diagnostic techniques and systems treatments of high efficacy, I is posible to reconsider the possibility of modifying the natural history of the advanced disease through the its early diagnosis.Tomography by Emission of Positrons (PET) with 18FDG (18-fluordeoxiglucose) in the diagnosis and monitoring the therapeutic response of breast cancer, as of other clinical applications of PET, has developed rapidly in recent years, demonstrating its diagnostic efficacy. In the breast cancer its use has been proposed in different fields: 1) screening or detection of the breast of cancer in young women with dense breast (great fibrous component) or with silicone implants where mammography suffers from a low specificity (30%), 2) in staging axillary nodes in mammary tumors of external quadrants and in lymph nodes of the internal mammary chain when the tumor is located in internal quadrants. The involvement of lymph nodes at the moment of the diagnosis, is in and of itself, the most important prognostic factor. In this way, 72% of women with pathologically negative nodes continues alive at 5 years, only 59% white one to three positive nodes and 41% with 3 o more positive lymph nodes, 3) in the loco-regional staging and also at distance localization of breast lesions locally invasive, contributing to the detection of metastatic disease in a single exploration and helping to decide the treatment more appropriately, 4) in the restaging of recurrence disease of breast of cancer, before the elevation serum of tumor markers (Ca 15.3), in clinically suspected patients and/or before diagnostic imaging negative or not conclusive findings and 5) monitoring therapy response. Recent research has valued the impact that the result of the PET has in the therapeutic management of the patients with cancer of the breast with very good perspectives. The objective of the clinical case that we present is to emphasize the great utility of the PET in the diagnosis of recurrent disease of breast cancer treated with radiological findings non-conclusive and with clinical suspicion of recurrent disease, as well as in monitoring and evaluation of the response to the therapy applied.
Alasbimn Journal. 01/2004;
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M D Green,
H Koelbl,
J Baselga,
A Galid, V Guillem,
P Gascon,
S Siena,
R I Lalisang,
H Samonigg,
M R Clemens,
V Zani,
B C Liang,
J Renwick,
M J Piccart
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ABSTRACT: We evaluated the efficacy of a single fixed 6 mg dose of pegfilgrastim (a pegylated version of filgrastim) per cycle of chemotherapy, compared with daily administration of filgrastim, in the provision of neutrophil support.
Patients (n = 157) were randomized to receive either a single 6 mg subcutaneous (s.c.) injection of pegfilgrastim or daily 5 mg/kg s.c. injections of filgrastim, after doxorubicin and docetaxel chemotherapy (60 mg/m(2) and 75 mg/m(2), respectively). Duration of grade 4 neutropenia, depth of neutrophil nadir, incidence of febrile neutropenia, time to neutrophil recovery and safety information were recorded.
A single 6 mg injection of pegfilgrastim was as effective as daily injections of filgrastim for all efficacy measures for all cycles. The mean duration of grade 4 neutropenia in cycle 1 was 1.8 and 1.6 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2-4 were consistent with the results from cycle 1. A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim (13% versus 20%, respectively). A single fixed dose of pegfilgrastim was as safe and well tolerated as standard daily filgrastim.
A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim in safely providing neutrophil support during myelosuppressive chemotherapy. Pegfilgrastim may have utility in other clinical settings of neutropenia.
Annals of Oncology 02/2003; 14(1):29-35. · 6.43 Impact Factor
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R García-Carbonero,
J I Mayordomo,
M V Tornamira,
M López-Brea,
A Rueda, V Guillem,
A Arcediano,
A Yubero,
F Ribera,
C Gómez,
A Trés,
J L Pérez-Gracia,
C Lumbreras,
J Hornedo,
H Cortés-Funes,
L Paz-Ares
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ABSTRACT: Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate-in a prospective multicenter randomized clinical trial-the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia.
A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count <100/mm(3)), short latency from previous chemotherapy cycle (<10 days), sepsis or clinically documented infection at presentation, severe comorbidity, performance status of 3-4 (Eastern Cooperative Oncology Group scale), or prior inpatient status. Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 microg/kg per day). The primary study end point was the duration of hospitalization. All P values were two-sided.
Patients randomly assigned to receive G-CSF had a significantly shorter duration of grade IV neutropenia (median, 2 days versus 3 days; P = 0.0004), antibiotic therapy (median, 5 days versus 6 days; P = 0.013), and hospital stay (median, 5 days versus 7 days; P = 0.015) than patients in the control arm. The incidence of serious medical complications not present at the initial clinical evaluation was 10% in the G-CSF group and 17% in the control group (P = 0.12), including five deaths in each study arm. The median cost of hospital stay and the median overall cost per patient admission were reduced by 17% (P = 0.01) and by 11% (P = 0.07), respectively, in the G-CSF arm compared with the control arm.
Adding G-CSF to antibiotic therapy shortens the duration of neutropenia, reduces the duration of antibiotic therapy and hospitalization, and decreases hospital costs in patients with high-risk febrile neutropenia.
JNCI Journal of the National Cancer Institute 02/2001; 93(1):31-8. · 13.76 Impact Factor
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J L González-Larriba,
S Serrano,
M Alvarez-Mon,
F Camacho,
M A Casado,
J L Díaz-Pérez,
E Díaz-Rubio,
L Fosbrook, V Guillem,
J J López-López,
J A Moreno-Nogueira,
J Toribio
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ABSTRACT: In the randomised clinical trial E1684, the administration of interferon (IFN) alpha-2b resulted in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection. However, and considering the cost and toxicity of IFN, the convenience of its widespread use should be evaluated. The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group. A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years, according to the clinical outcome of the E1684 study. The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient's lifetime. The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model. The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome. In conclusion, in high-risk melanoma patients following surgical resection, the cost-effectiveness of IFN alpha-2b (at a dose of 20 MU/m2/day, 5 days per week for one month, followed by 10 MU/m2 TIW, up to one complete year of therapy) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System.
European Journal of Cancer 01/2001; 36(18):2344-52. · 5.54 Impact Factor
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J Bellmunt, V Guillem,
L Paz-Ares,
J L González-Larriba,
J Carles,
E Batiste-Alentorn,
A Sáenz,
M López-Brea,
A Font,
M Nogué,
R Bastús,
M A Climent,
J J de la Cruz,
J Albanell,
J M Banús,
E Gallardo,
E Diaz-Rubio,
H Cortés-Funes,
J Baselga
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ABSTRACT: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium.
Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles.
Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up.
This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.
Journal of Clinical Oncology 09/2000; 18(18):3247-55. · 18.37 Impact Factor
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ABSTRACT: Transitional cell carcinoma (TCC) of the urothelium is a highly chemosensitive tumour. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. At present, the combination of cisplatin, methotrexate, doxorubicin and vinblastine (M-VAC) is the most widely used for advanced TCC with an overall response rate of 40-72% in phase II, and 35-45% in phase III studies, and a median survival of approximately 12 months. These modest results and the unsuccessful attempts to increase efficacy with dose intensive M-VAC schedules have prompted the identification of new active agents in TCC, such as the taxanes and gemcitabine. The overall response rates for two-drug regimens of cisplatin-paclitaxel, carboplatin-paclitaxel and cisplatin-gemcitabine range from 63 to 72%, 14 to 65% and 42 to 66%, respectively. The overall response rates for platinum-paclitaxel-gemcitabine three-drug regimens range from 58 to 80%. The potential clinical benefit of these new three-drug combinations in the treatment of TCC needs to be tested in future phase III studies.
European Journal of Cancer 08/2000; 36 Suppl 2:17-25. · 5.54 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the toxicity and efficacy of paclitaxel/gemcitabine administered every 2 weeks in the first-line treatment of advanced breast cancer. Forty-three chemonaive patients with histologically confirmed metastatic breast carcinoma were enrolled. Patients received paclitaxel 150 mg/m2 followed by gemcitabine 2,500 mg/m2, both on day I of a 14-day cycle, for a maximum of eight cycles. Thirty-four patients were evaluable for toxicity; 38 were evaluable for efficacy. The median age at the time of diagnosis was 54 years, the median performance status was 90, and the median number of lesions was three. Most patients (71%) had received prior adjuvant therapy. Grade 3 and 4 toxicity was limited to leukocytes (14% and 18%, respectively). Grade 3 toxicities (5% each) were thrombocytopenia, nausea and vomiting, elevation of aspartate transaminase, neurosensory, and constipation. One patient had neutropenia and fever. The objective response rate was 68% (21% complete response and 47% partial response); 18% had stable disease and 13% had partial disease. The preliminary evaluation of paclitaxel/gemcitabine given as a 2-week schedule to patients with untreated advanced breast carcinoma shows encouraging activity and a favorable toxicity profile.
Seminars in Oncology 03/2000; 27(1 Suppl 2):20-4. · 3.50 Impact Factor
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ABSTRACT: The aim of this study is to evaluate the prognostic significance of c-erbB-2/neu amplification and epidermal growth factor receptor (EGFR) expression in primary breast cancer (BC) and their prognostic implications when combined with estradiol receptor (ER) status. In this work, 825 BCs were studied. Neu amplification was evaluated by dot-blot and EGFR expression was evaluated by ligand binding assay using I125-EGF. Neu, EGFR, estradiol and progesterone receptors (ER and PR) had a marked influence on disease free survival (DFS) in univariate analysis. In node-negative (NO) cases only neu was associated with short DFS (p = 0.005). However, in node-positive (N+) cases both EGFR (p = 0.005) and neu (p = 0.002) influenced DFS. None of the biological markers were significant predictors for overall survival (OS) in NO/BC. On the contrary, in N+/BC, EGFR + (p = 0.003) was associated with short OS. The EGFR + /neu/phenotype represented a sub-group with an even worse prognosis with respect to DFS (p = 0.0034) as well as EGFR + /ER-tumors (p = 0.005). Moreover, neu + /ER-patients also had a high probability of relapse (p = 0.0000) and death (p = 0.006). C-erbB-2/neu, EGFR, histological grade, pN, pT and ER were subjected to a Cox multivariate regression analysis: neu was the most important parameter in predicting recurrence, and EGFR was a significant predictor for OS.
Clinica Chimica Acta 07/1997; 262(1-2):99-119. · 2.54 Impact Factor
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ABSTRACT: The present study attempts to clarify the specific contribution of cathepsin D (CD) and pS2 to the progression of breast cancer (BC) by examining the relationship between these two factors and TNM status, tumour grade, estradiol receptors (ER) and the prognosis factors epidermal growth factor receptor (EGFR) and neu amplification in a group of 270 BC patients. CD and pS2 were determined by an immunoradiometric procedure in tumour cytosols obtained for ER. Neu amplifications were evaluated by dot-blot, in tumour DNA. EGFR was determined in membrane tumour preparations obtained from ER cytosols by a two-point radiometric saturation assay. CD is basically related to bad prognosis factors and has a direct correlation with tumour size (P = 0.025) and EGFR content (P = 0.007) and is associated with the presence of metastases (P = 0.000). pS2 is mostly related to good prognosis factors and showed an inverse correlation with the Scarff-Bloom Index (P = 0.011) and a direct correlation with ER content (P = 0.014). Finally, pS2 and CD also showed a strong mutual association (P = 0.009) and the fact that both correlated with ER content confirms in tumours the experimental finding that they are estrogen-induced proteins.
Clinica Chimica Acta 04/1996; 247(1-2):89-103. · 2.54 Impact Factor
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ABSTRACT: We report 18 consecutive patients with testis cancer and retroperitoneal residual masses with normal tumor markers, who underwent lymphadenectomy. Aiming to preserve the antegrade ejaculation, we carried out surgical modifications which basically attempt to preserve: (1) both sympathetic lumbar trunks, (2) the superior hypogastric plexus and (3) some of the postganglionic branches. With a mean follow-up of 28.1 months (range 6-62 months), 15 (83.3%) of the 18 patients preserved ejaculation, without significant differences between ejaculation volumes before and after lymphadenectomy. At the present time, 3 of 4 possible patients have fathered children. Mass size seems to be an important predictive factor of ejaculation preservation. One patient relapsed in the retroperitoneal dissection area, representing a recurrence rate of 5.5%. The disease-free survival rate was 94.4%, and 1 patient died due to disease progression with lung recurrence. Thus preservation of ejaculation was possible in most of these patients.
European Urology 02/1994; 25(3):199-203. · 8.49 Impact Factor
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ABSTRACT: Seventy metastatic breast adenocarcinoma patients, pretreated with standard hormonotherapy or chemotherapy, received continuous UFT at 10 mg/kg/day, orally, for at least two months. There were one complete response (1.5%), 12 partial responses (17%), one minor response and 37 disease stabilizations. The median duration of response was nine months. A greater efficacy was demonstrated in 29 patients with soft tissue disease, with a rate of 38% objective responses. The major toxicity was gastrointestinal, with 45% of patients developing nausea and vomiting and 30%, diarrhea. Bone marrow toxicity was slight. UFT has shown antitumor activity in our group of pretreated patients, especially these with the cutaneous tumoral and/or inflammatory form of the disease.
Japanese Journal of Clinical Oncology 01/1994; 23(6):363-5. · 1.78 Impact Factor
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ABSTRACT: Epidermal growth factor (EGF) and its receptor (EGFR) were measured in 60 breast cancers (BC), 6 benign mammary tumors (BM), 8 samples of normal breast (NB), 6 endometrial carcinomas (EC) and 30 lung cancers (LC). EGF was measured in plasma, saliva and urine from 20 patients with BC, before and after tumor excision, and in 8 patients with metastatic disease. The median EGF in BM and BC was significantly higher (P < 0.05) than in NB. No significant correlation between EGF and EGFR was found in BC. Neither tumor excision nor the spreading of the disease significantly modified the EGF concentrations in biological fluids. In LC there was an inverse relationship between EGF and EGFR (rs = -0.36; P = 0.09), which disappeared in normal lung. It is concluded that EGF may play a role in malignant transformation; however, the weak correlation between EGF and EGFR lessens the importance of EGF in either autocrine or paracrine stimulation of tumor growth.
Clinica Chimica Acta 05/1993; 215(1):51-61. · 2.54 Impact Factor
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European Journal of Cancer 02/1993; 29A Suppl 1:S33-4. · 5.54 Impact Factor
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ABSTRACT: The present article studied the biological behaviour of T4a versus T4b tumors. Of 29 patients with T4a tumors, 24 were treated by radical cystectomy and 5 were treated by diversion alone on detecting pathologic gross adenopathies at laparotomy. Of these 10/28 (35.7%) are alive and tumor-free. Of 11 patients with T4b tumors, 7 were initially treated with systemic chemotherapy (6 M-VAC and 1 5-FU + ADM) which achieved a clinical response in 4; 1 (14.2%) was RCc. Posteriorly, all these patients underwent radical cystectomy that revealed 2 had RPp and 2 had tumor progression (N+), accounting for an RPp rate of 28.5% and tumor progression of 71.5%. Overall, with a mean follow-up of 13.3 months, only 1 patient is tumor free. The foregoing findings show the different behaviour of these two groups of patients with an incidence of tumor positive adenopathies of 48.2% and 72.7% and tumor-free survival of 35.7% and 9.0% for patients with T4a and T4b, respectively.
Archivos españoles de urología 02/1990; 43 Suppl 2:205-8.
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C Gaspar,
E Zapater,
M Chust,
M A Climent,
E Ferrándis,
M A Muñoz,
J L Mengual,
A Berrocal,
B J Vendrell,
L Arribas, V Guillem
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ABSTRACT: This was a retrospective study of 98 patients (pts.) with histologically confirmed nasopharyngeal carcinoma. The clinico-demographic characteristics were: median age of 53 years (11-83); 74 males and 24 females (ratio 3:1); histology subtype OMS 2-3 in 89 pts. (90.8%); cranial nerve deficits in 11 pts. (11.2%); 50 (51%) were stage T3T4; 68 pts. (69.4%) N2N3 and 77 pts. (78.6%) stage IV. The therapeutic modalities were: radical radiotherapy (RT) alone in 42 pts., chemotherapy (CT) alone in 4 pts., RT + adjuvant CT in 10 pts. and neoadjuvant CT + RT in 42 pts. RT was delivered in wide fields, doses between 50-75 Gy with conventional fractionation. CT consisted in cisplatinum-based schedules (PF in 34 pts., BEC in 9 and others in 13 pts.). Analyzed by treatment, more males and stages N2N3 and IV were accrued in neoCT + RT arm (p < or = 0.05). For the entire population, the overall complete response was achieved in 65 pts. (66.3%); in 27/35 pts. (77.1%) of the RT group and 30/51 pts. (58.8%) of CT + RT group (p 0.07) of pts. with III-IV stages. With a median follow-up of 74.5 months, 32 pts. (32.65%) are alive and free of disease. The projected OS for all pts. was 40 months (m), 51.4% at 3 years (y) and 45.5% at 5 y with a disease free survival of 37 m (0-236). No differences between treatment arms were found (p 0.4). In univariant analysis for OS in stage III-IV pts., age > 50 y, histology OMS1, cranial nerve deficits, stage T3T4 and N2N3, were considered adverse prognostic factors (p < or = 0.05). In multivariant analysis, only age > 50 y and stages T3-T4, N2-N3 were significant (p < or = 0.05). In conclusion, we demonstrated good long term survival without any differences among treatment modalities in pts. with advanced nasopharyngeal carcinomas. New therapeutic approaches are warranted in order to improve the outcome of this patients.
Acta Otorrinolaringológica Española 51(8):691-6.
