Joaquín Montalar Salcedo

Hospital Universitari i Politècnic la Fe, Valenza, Valencia, Spain

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Publications (24)38.09 Total impact

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    ABSTRACT: Sorafenib is the standard treatment of patients with advanced hepatocellular carcinoma (HCC), with demonstrated outcome benefits in randomized clinical trials. We present a single-center experience with sorafenib with the aim to establish its efficacy and safety in daily clinical practice. A total of 62 patients were treated with sorafenib 400 mg/12 h until disease progression or unacceptable toxicity. Response rates, incidence of adverse events, actuarial disease-free survival, and overall survival (OS) were estimated. Univariate and multivariate analyses of prognostic factors for survival were also performed. Median treatment duration was 92 days. A 43 % disease control rate was achieved (partial response, 15 % and disease stabilization, 28 %). After a median follow-up of 24.1 months, the median progression-free survival and OS for the overall population were 5.8 and 6.7 months, respectively, with survival rates of 27 % at 1 year and 17 % at 2 years. The most common grade 3-4 adverse events were fatigue (19 %), hand-foot syndrome (8 %), hypertension (5 %), and diarrhea (3 %). The univariate analysis showed that patient performance status (PS), use of previous treatments, and albumin >3.5 g/dL were significant prognostic factors for survival. In the multivariate study, only PS, alcoholic etiology and albumin >3.5 g/dL remained as independent predictors of survival. Sorafenib is a safe and moderately effective drug in HCC, although patients must be properly selected before starting therapy. Baseline PS, Barcelona Clinic Liver Cancer staging, and liver function should be taken into account as prognostic factors. Results in daily practice are somewhat inferior than observed in clinical trials.
    No preview · Article · May 2014 · Medical Oncology
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    ABSTRACT: We present the case of a 60-year-old man with a primary pulmonary melanotic schwannoma treated with surgery and who developed an orbital and myocardial relapse 2 years after the initial diagnosis. Melanotic schwannomas are rare pigmented tumours that tend to arise from the peripheral nerves near the midline. A primary lung presentation, as in our case, is extremely rare. In more than half of cases, the Carney triad of myxomas of the heart, skin and breast, spotty pigmentation and endocrine hyperactivity is present. A thorough pathological study is pivotal for a correct diagnosis. The main differential diagnosis is with metastases of malignant melanoma. The biological behaviour is unpredictable. Treatment should include radical surgery if possible; the role of chemotherapy and radiotherapy is uncertain due to the rarity of the tumour.
    No preview · Article · Jul 2010 · Clinical and Translational Oncology
  • Alejandra Giménez Ortiz · Joaquín Montalar Salcedo
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    ABSTRACT: Heat shock proteins are ubiquitous molecular chaperones involved in posttranslational folding, stability, activation and maturation of many proteins that are essential mediators of signal transduction and cell cycle progression. Hsp90 proteins are the best studied proteins of this family. A growing number of Hsp90 client proteins have been shown to be important for the development, proliferation and survival of several types of cancer. Inhibition of Hsp90 leads to the degradation of known oncogene products, such as Her2, BRAF and others, leading to the simultaneous blockade of multiple oncogenic transduction pathways. Hsp90 inhibitors, derived from the natural compound geldanamycin, are attractive targets for anticancer drug development. We will review the clinical data on Hsp90 inhibitors in different malignancies. The best known of them, 17-AAG, has shown significant antitumour activity against a broad variety of cancers in preclinical studies, including breast, myeloma, melanoma, prostate and lung cancers. Hsp90 inhibitors can be used as single agents or in combination with other targeted treatments or chemotherapy and radiotherapy. The results of clinical phase II and III trials evaluating the effi cacy of these drugs in different types of tumours are awaited.
    No preview · Article · Mar 2010 · Clinical and Translational Oncology
  • María Martín Ureste · Regina Gironés Sarrió · Joaquín Montalar Salcedo
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    ABSTRACT: Non-small-cell lung cancer (NSCLC) ranks among the neoplasms with the worst prognoses and the highest mortality rates. Several factors, mainly clinical, are known that provide a predictive value on the course of the disease. In the era in which we live, the molecular basis of cancer is studied in depth and several molecular markers have been described that could play a prognostic role or that could predict the probability of responding to the different treatments used. Moreover, some mechanisms have been proposed that could explain primary or acquired resistance to treatment with chemotherapy and to targeted therapies. Knowing all these pathways is very important, as it allows the development of selective therapeutic strategies that minimise toxicity and optimise treatment effectiveness. However, the data obtained yield results that are at times contradictory, prospective studies with biomarkers thus being necessary so that their role can be established with the necessary evidence.
    No preview · Article · Feb 2010 · Clinical and Translational Oncology
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    ABSTRACT: The polymorphic genetic differences among individuals may modify the high risk for breast cancer (BC) and/or ovarian cancer (OC) susceptibility conferred by BRCA1 and BRCA2 mutations. In the present study we investigate the relevance of RAD51 -135C > G, TP53 R72P, NQO1*2 and CASP8 D302H polymorphisms as potential modifiers of BC and/or OC susceptibility conferred by these mutations. The study group encompasses 390 BRCA1/BRCA2 mutation carriers (182 affected with BC and/or OC and 208 unaffected) of 131 unrelated families studied in the Program of Genetic Counselling on Cancer of Valencia Community. The polymorphisms were detected in genomic DNA by ASRA method or real time PCR using fluorescently labeled probes. We found similar incidence of RAD51 -135C > G, TP53 R72P and NQO1*2 polymorphisms among affected and unaffected individuals considering BRCA1/BRCA2 mutations together and separately. However, the CASP8 D302H polymorphism was strongly associated with the absence of BC [OR = 3.41 (95% CI 1.33-8.78, P = 0.01)]. In fact, in the females with CASP8 D302H polymorphism the BC appeared at a median age of 58 in opposition to the 47 years observed for the wild type subjects (P = 0.03). Furthermore, the CASP8 D302H positive females showed a 50% probability of being free of BC by the age of 78 versus the 2% of the CASP8 negative ones. Our results support that the presence of the CASP8 D302H polymorphism diminishes the high risk of BC conferred by BRCA1 and BRCA2 mutations, making possible that some of the carriers could escape from suffering BC along their life span.
    Full-text · Article · Feb 2009 · Breast Cancer Research and Treatment
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    ABSTRACT: To identify clinical and biologic variables with significant impact on survival in patients with carcinomas of an unknown primary site (CUP) and to develop a simple prognostic model. In this retrospective study, univariate and multivariate prognostic factors analyses were conducted in a population of 100 patients with CUP. Patients with features requiring well defined treatments had previously been excluded. Overall survival (OS) was significantly related to the following pretreatment adverse prognostic clinical factors: a poor performance status (2 or 3), weight loss more than 10% in the last six months, the presence of liver metastases and more than two metastatic sites. Two biological parameters predicted a significantly shorter survival: elevated serum levels of alkaline phosphatase and of lactate dehydrogenase. In the multivariate analysis, only two independent adverse prognostic parameters were retained: a poor performance status and the presence of liver metastases. We developed a prognostic model for OS based on the following subgroups: good prognosis (PS 0 or 1 and absence of liver metastases), intermediate prognosis (PS> or =2 or presence of liver metastases) and poor prognosis (PS> or =2 or presence of liver metastases). Median OS for the three groups was 10.8, 4 and 1.9 months respectively, p<0.0001. A simple prognostic model using performance status and presence of liver metastases was developed. It allowed the assignment of patients into three subgroups with different outcomes. Treatment strategies could be adapted for each subgroup. We think that this prognostic model could be useful and should be validated in other patient series.
    No preview · Article · Aug 2007 · Clinical and Translational Oncology
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    ABSTRACT: Malignant mesothelioma is an insidious neoplasm arising from the mesotelial surfaces, of the pleural and peritoneal cavities, the tunica vaginalis, or the pericardium. The predominant cause is inhalation exposure to asbestos. We present a rare case of primary malignant mesothelioma of the peritoneum in a 64 year old man without history of inhalation exposure to asbestos. The initial symptoms were constitutional syndrome and right pleural effusion. Positron emission tomography combined with computed tomography (PET/TC) was useful for a supporting diagnosis and to determine the extension. The patient received treatment with systemic palliative chemotherapy, cisplatin-pemetrexed. After three cycles, partial response was observed, but the evolution was fatal due to secondary toxicity of chemotherapy.
    No preview · Article · Mar 2007 · Anales de medicina interna (Madrid, Spain: 1984)
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    ABSTRACT: Malignant mesothelioma is an insidious neoplasm arising from the mesotelial surfaces, of the pleural and peritoneal cavities, the tunica vaginalis, or We present a rare case of primary malignant mesothelioma of the peritoneum in a 64 year old man without history of inhalation exposure to asbestos. The initial symptoms were constitutional syndrome and right pleural effusion. Positron emission tomography combined with computed tomography (PET/TC) was useful for a supporting diagnosis and to determine the extension. The patient received treatment with systemic palliative chemotherapy, cisplatin-pemetrexed. After three cycles, partial response was observed, but the evolution was fatal due to secondary toxicity of chemotherapy.
    No preview · Article · Jan 2007 · Anales de medicina interna (Madrid, Spain: 1984)
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    ABSTRACT: Recent studies have suggested a rise in the incidence of testicular germ-cell tumors (TGTs) in the last years, mainly due to an increase of early stage cases. We analysed the time trends in biological features of these patients in order to confirm this tendency in our environment. The clinical records of 136 consecutive patients with TGTs treated at a single institution over a 20-year period (1984-2003) were retrospectively reviewed. Pathological, clinical, therapeutic and outcome data were collected. Patients were allocated into four consecutive 5- year intervals and their characteristics were compared by means of the chi-squared test. The survival analysis was performed with the method of Kaplan and Meier. A progressive increase in the incidence of new cases, and a more frequent diagnosis of stage I versus stage II-IV disease was confirmed within this time period. It was also observed a greater use of postorchiectomy chemotherapy, mainly due to an increase in the adjuvant indications. A significant decrease in the recurrence rate was noted. Ten-year overall survival was 86.5%. There was a trend for improved outcome, but the differences among the two decades were not statistically significant. A real increase in the incidence of TGTs and in the proportion of early stages was confirmed. This may be due to an epidemiological change or to an earlier diagnosis. This new pattern is associated with a more frequent use of adjuvant chemotherapy and with a reduction in the relapse rate.
    No preview · Article · Sep 2006 · Clinical and Translational Oncology

  • No preview · Article · Jul 2005 · Lung Cancer
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    ABSTRACT: Extra-pulmonary small cell carcinoma (ESCC) is as a pathologic entity distinct from small cell lung carcinoma (SCLC). ESCC is considered a systemic disease in its origin, so the therapeutic approach is similar to SCLC with chemotherapy being considered in case of extensive and local disease. We present a retrospective comparison of ESCC and SCLC in our institution. Using the tumour registry database of Hospital Universitario La Fe we reviewed 24 ESCC cases receiving attention between 1987 and 2003, and these were compared with a series of 341 patients with SCLC in the same institution. Of the 24 patients with ESCC 19 were men and 5 were women with an average age of 58 years (range 23 to 85). The most frequent site was the mediastinum with 58% having extensive disease. All patients but one received treatment. The therapeutic approaches were local and systemic in 13 patients, systemic alone in 6 and local alone in 4. Schedules based on platinum and etoposide were used. The median follow-up was 53 months (range 4 to 211). Median survival was 18.9 months; 30 in patients with local disease and 8 in those with extensive disease. In the SCLC series of patients, there were 336 men and 5 women; 62% having extensive disease. The median survival was 10 months; 12 months in those patients with local disease and 8 in those with extensive disease. The overall survival of patients with ESCC was slightly better than patients with SCLC. ESCC with local disease had a better survival outcome than SCLC with local disease. Chemotherapy is the cornerstone of the treatment, but sometimes local treatment could be sufficient.
    No preview · Article · Apr 2005 · Clinical and Translational Oncology
  • J. Aparicio Urtasun · R. Gironés Sarrió · J. Montalar Salcedo
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    ABSTRACT: Cancer patients usually present deficient defensive mechanisms that predispose them to the development of infectious diseases. Some of these are inherent to the host features, whereas others are related to the underlying neoplasm itself or the use of diagnostic techniques or treatment procedures. Bacterial infections represent a main cause of mortality. The most common processes are located at the respiratory tract, oro-pharyngeal cavity, skin and perineal area, or are related to the use of indwelling venous catheters, although bacteraemia without an evident focus is also frequent. These infections use to have a latent course, with scant inflammatory symptoms at early stages. However, their evolution is atypical and present a marked tendency to progress and develop severe sepsis. Diagnosis rests on clinical suspect and diagnostic explorations directed to the most probable foci. However, most authors recommend the early onset of broad-spectrum antibiotic therapy, especially when fever and neutropenia are associated. If the process is not controlled this way, invasive diagnostic procedures and intensive supportive care are indicated.
    No preview · Article · Jan 2005 · Revisiones en Cancer

  • No preview · Article · Jan 2005
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    ABSTRACT: We undertook a prospective study to determine the feasibility, toxicity, response and survival rate of simultaneous chemotherapy (CT) and radiotherapy (RT) for locally-advanced head and neck cancer. Fifty eight patients were treated with carboplatin (i.e. 100 mg/m(2)) weekly, tegafur-uracil (UFT) (oral 400 mg/m(2)) daily and simultaneous treatment with a cobalt-60 source of radiation (total dose 65-70 Gy). Forty six patients (79%) received the total dose of RT while CT was delayed or reduced in 31 patients (53%). Grade 3-4 toxicity observed was mucositis in 27 (47%), leukopenia in 10 (17%), anaemia in 5 (9%), and diarrhoea in 4 (7%) patients. The objective response rate was 74%; 24 complete response (41%) and 19 partial response (33%). Overall, there are 11 patients (19%) disease-free, 7 (12%) alive with disease, 35 have died of progressive disease (60%) and 3 (5%) from other causes. There were 2 toxic deaths (3%). Median time to progression was 10 months and median survival was 18.4 months. The use of carboplatin and UFT concomitant with radiotherapy has, in our study, a slightly lower activity than other chemo-radiotherapy protocols, especially with respect to complete responses, but with no significant differences in overall survival or disease-free survival rates.
    No preview · Article · Jan 2005 · Clinical and Translational Oncology
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    ABSTRACT: Introduction. Despite significant advances in the palliative care of cancer patients with terminal disease, a considerable proportion of them still die at hospital. The causes of this fact are multiple including sociocultural, familial, and sanitary reasons. Material and methods. A retrospective study was performed on the place and cause of death among patients treated at a Department of Medical Oncology in two time periods (10/1996–10/1997 and 2001) in order to assess the actual situation and its evolution through the last years. Our department assumes both the active treatment and the palliative care of patients assigned to its area. In 2001, 1,254 new cases were referred and 1,006 hospital admissions were recorded, with a median stay of 11 days. In the same period, 424 patients died. Results. Of them, 250 (59%) deaths occurred at hospital (25% of the department discharges). The most common neoplasms were lung (24%), colorectal (14%), and breast (9%). The median hospital stay was 8 days (range, 1–60). The causes of death were cancer progression (79%), intercurrent diseases (11%), and complications during active treatment (10%). In comparison with the former group, among patients dying at home there was a greater relative percentage of women, diagnoses of breast cancer, lymphoma and multiple neoplasms, elderly patients, and deaths due to tumor progression. Conclusions. Nearly 60% of cancer patients who die in our environment do it at hospital. Of them, 20% do not die specifically of tumor progression. The pattern of deaths at home is somewhat different. Sanitary resources should be adapted to the particular care features of each department, favoring the development and coordination of palliative care units, both hospital-based and home care teams.
    No preview · Article · Nov 2004
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    ABSTRACT: Introduction. Ewing's sarcoma is a highly malignant small round-cell tumor arising primarily from bone. Adults with this neoplasm have a poorer survival than that of children. The Spanish Society of Paediatric Oncology (SEOP) recommends that high-risk patients be treated with a combination of 5 different drugs (EVAIA schedule). The objective of this study is to evaluate response, overall survival, dose intensity and toxicity of the SSOP protocol in adult patients with high-risk Ewing's sarcoma. Material and methods. Between 1997 and 2001, 16 adults with a histological diagnosis of high-risk Ewing's sarcoma were treated according to SEOP recommendations. Median age was 23 years (range: 15-42). Enneking staging system indicated 7 patients (44%) were II-B and 9 patients (56%) at stage III. Results. The responses were: 12 complete responses (75%), 1 partial response (6%), 2 patients with stable disease and 1 disease progression. At the time of the present analysis, 6 patients (38%) were alive and free of disease, 1 (6%) was alive with disease and 9 patients had died (8 of them due to disease progression and 1 secondary to a second line chemotherapy administered after EVAIA). Median survival was 21 months (range: 9-67) and median time to progression was 14 months (range: 6-23). Conclusions. EVAIA protocol is an aggressive regimen in which the most frequent toxicity is granulocytopenia and anaemia. In our experience no deaths were due to this protocol. The use of EVAIA in first-line therapy achieved 81% response rate with a high rate of long-term survival in this patient population with poor prognosis.
    No preview · Article · Apr 2004 · Clinical and Translational Oncology
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    ABSTRACT: Purpose: When comparing single agent versus combination therapy with gemcitabine and cisplatin in non-small cell lung cancer (NSCLC), several studies indicate a response rate of 20-28% for monotherapy with gemcitabine, and a response rate of 40% for combination therapy with gemcitabine and cisplatin. We study here the activity of this combination. Material and methods: Between June 1998 and October 1999 a phase II trial was made in 26 patients with NSCLC, 19 in stage III-B and 7 in stage IV. The treatment schedule consisted in gemcitabine 1200 mg/sq m days 1 and 8, and cisplatin 100 mg/sq m day 1, repeated in cycles every 21 days. Results: 105 cycles were administered. The overall median of dose intensity was 88%. The adverse effects observed were: Grade 34 thrombocytopenia (37%), grade 3-4 neutropenia (31%), and grade 3 emesis (23%). The objective response rate was 53.8% (Cl 95%: 40-80%), including 14 partial responses; complete responses were not seen. Eighteen patients (69%) received radiotherapy as local treatment. The median time to disease progression was 5 months. The mean survival was 12 months. The survival rate at 18 months was 38%. Conclusions: The combination used in this phase II trial is useful for the patients with stages III-B and IV NSCLC. The toxicity can be considered as acceptable.
    No preview · Article · Jan 2000
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    ABSTRACT: Purpose: To determine the efficacy of ofloxacin in the management of febrile neutropenic cancer patients. Material and methods: A prospective study in 57 cases of neutropenic fever in 51 patients is made. All the patients were treated with ofloxacin (200 mg every 12 h), first intravenously, and then orally. The patients were randomized to receive or not granulocyte colony-stimulating factor (G-CSF). Results: The existence of infection was microbiologically documented in 32% cases, clinically documented in 30%, and probable or doubtful in 38%. The mean of absolute neutrophil count was 183 ± 200 (range 0-500). The mean of neutropenia duration was 4.8 ± 2.4 days in patients who received G-CSF, and 4.7 ± 3.4 days in patients without G-CSF. The antibiotic was administered for a mean of 8.5 ± 3.8 days. The percentage of responses was 63% in both groups. We had to add another antibiotic or to substitute the ofloxacin for failure in the treatment in 14% of the episodes. Six patients died during the treatment. Conclusions: The ofloxacin is effective in the management of neutropenic fever. The advantage of this treatment is its oral administration after the acute phase. Ofloxacin has easier administration and reduces the number of days in the hospital. The association with G-CSF does not reduce the neutropenia duration.
    No preview · Article · Jan 1999
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    ABSTRACT: Multiple primary neoplasms are increasing in clinical practice, which is mainly due to the longer survival of cancer patients. Radiotherapy at an early stage of Hodgkin disease or lymphoma is well known to be associated with the future occurrence of secondary thyroid cancer. Nevertheless, the synchronous presentation of these two types of neoplasms is exceptional. We report here three cases of synchronic diagnosis of thyroid carcinoma and a malignant lymphoproliferative disease in patients who had not previously received radiotherapy nor chemotherapy. In malignant tumours of synchronic presentation, there is usually and underlying genetic predisposition involved in the etiology. In our patients, no carcinogenic environmental factor was demonstrated and, while this neoplastic association might be casual, an investigation on the possible individual predisposing factors would be warranted.
    No preview · Article · Dec 1997 · Revista Clínica Española

  • No preview · Article · Jan 1994 · Annals of Oncology