Fernandez-Hidalgo, Ó. (Óscar)
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- High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients(Springer Nature, 1996) Subira, M.L. (María L.); Martin-Algarra, S. (Salvador); Aristu-Mendioroz, J.J. (José Javier); Brugarolas, A. (A.); Gurpide, A. (Alfonso); Vieitez, J.M. (J. M.); Aramendia, J.M. (J.M.); Vanaclocha, V. (V.); Rebollo, J. (J.); Moreno-Palanques, R. (R.); Fernandez-Hidalgo, Ó. (Óscar)A phase II study of postoperative high-dose carmustine (HDBCNU), intracarotid cisplatin (CDDP), and radical radiotherapy in patients with high-grade glioma was performed. Patients underwent 4-6 consecutive days of blood hematopoietic progenitor cell (HPC) apheresis without prior mobilization. Chemotherapy included intracarotid CDDP, 60 mg/m2, and BCNU, 900 mg/m2. HPC were infused 48 h after HDBCNU. Whole brain irradiation, up to 50 Gy, was started on the 8th day after HPC infusion. With a median follow-up time of 44 months, median overall survival was 15.5 months. Eight patients (23.5%) are alive free of disease 2-6 years after treatment (seven out of 25 patients with glioblastoma multiforme and one out of nine patients with anaplastic astrocytoma). Survival was influenced by young age, good performance and complete surgical resection. Two patients (5.8%) died of therapy-related complications. Acute hematological toxicity of HDBCNU was moderate, with a full recovery on day 26. No acute pulmonary or hepatic toxicity was found. Late severe neurological toxicity was observed in one third of patients surviving beyond 2 years. We conclude that HDBCNU, 900 mg/m2, intracarotid CDDP and radical radiotherapy appear to benefit some patients with high-grade gliomas, and phase III studies should preferentially select young patients with resectable tumors.
- Ética médica e investigación clínica(Universidad de Navarra, 1989) Herranz, P. (Pilar); Gil, A.C. (A. C.); Brugarolas, A. (A.); Santos, M. (Manuel); Sierrasesumaga, L. (Luis); Calvo, F.A. (Felipe A.); Fernandez-Hidalgo, Ó. (Óscar)
- Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study(Nature, 2001) Garcia-Rayo, S. (S.); Martinez-Monge, R. (Rafael); Martin-Algarra, S. (Salvador); Brugarolas, A. (A.); Perez-Calvo, J. (Javier); Azinovic, I. (Ignacio); Rebollo, J. (J.); Martinez-Aguillo, M. (M.); Subira, L. (L.); Fernandez-Hidalgo, Ó. (Óscar)The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m2 plus doxorubicin 80 mg/m2 alternating every 14 days with paclitaxel 200-350 mg/m2 plus cisplatin 120 mg/m2. Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m2 plus etoposide 600 mg/m2 alternating with paclitaxel 200-350 mg/m2 plus ifosfamide 8 g/m2. Peripheral blood stem cells were infused after every course except the first, with a median CD34+ dose of 2.1 ´ 106/kg per cycle. Positive selection of CD34+ cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support.
- Tratamiento hormonal del cáncer de mama(Ediciones Universidad de Navarra, 2008) Espinos, J. (Jaime); Olier, C. (Clara); Santisteban, M. (Marta); Garcia-Foncillas, J. (Jesús); Hernandez, A. (A.); Cruz, S. (S.) de la; Fernandez-Hidalgo, Ó. (Óscar); Reyna, C. (Carmen)Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications.
- Quimioterapia complementaria del cáncer de mama; experiencia de la Clínica Universitaria de Navarra(Universidad de Navarra, 1990) Herranz, P. (Pilar); Zornoza, G. (Gerardo); Martin-Algarra, S. (Salvador); Azinovic, I. (Ignacio); Vieitez, J.M. (J. M.); Fernandez-Hidalgo, Ó. (Óscar); Muñoz, L. (L.)Desde 1982 a 1989 se han tratado 68 pacientes con carcinoma de mama. 57 han sido premenopáusicas y 11 postmenopáusicas. El estadio tumoral más frecuente ha sido T2N1 (44,1 %) seguido de T1N1 (20,6 %). La dosis media de quimioterapia recibida ha sido de 91,2 %, 88 % y 94 % para la ciclofosfamida, metotrexate y 5-fluorouracilo respectivamente. El tratamiento ha sido bien tolerado, siendo la toxicidad más frecuente la hematológica (leucopenia). Las pacientes premenopáusicas han presentado un intervalo libre de enfermedad de 89,4 % a 96 meses y las postmenopáusicas de 63,3 % a 68 meses. No se han observado diferencias en el intervalo libre de enfermedad según el tamaño del primario o la positividad del tumor a receptores de estrógeno o progesterona. Los factores pronósticos más importantes de esta serie han sido el número de ganglios axilares afectos y la dosis de quimioterapia recibida
- Síndrome terminal de enfermedad criterios y actitudes(Universidad de Navarra, 1988) Herranz, P. (Pilar); Anton-Aparicio, L.M. (L. M.); Gil, A.C. (A. C.); Brugarolas, A. (A.); Santos, M. (Manuel); Sierrasesumaga, L. (Luis); Calvo, F.A. (Felipe A.); Fernandez-Hidalgo, Ó. (Óscar)
- A single prior course of BCNU-cisplatin chemotherapy has a significant deleterious effect on mobilization kinetics of otherwise untreated patients(Nature Publishing Group, 2004) Martin-Algarra, S. (Salvador); Aristu-Mendioroz, J.J. (José Javier); Rifon, J. J. (Jose J.); Rocha, E. (Eduardo); Perez-Calvo, J. (Javier); Aramendia, J.M. (J.M.); Bendandi, M. (Maurizio); Prosper-Cardoso, F. (Felipe); Fernandez-Hidalgo, Ó. (Óscar)Extensive prior treatment with cytotoxic agents is associated with impaired mobilization of hematopoietic cells. To assess the effect of a single course of standarddose chemotherapy (CT), we compared the results of filgrastim-induced mobilization among two sequential groups of grade III–IV malignant glioma patients included in a hematopoietic transplantation program. The first group (21 patients) had never been treated with CT until 2 days after surgery, when they received a course of 100 mg/m2 BCNU (IV) and 100 mg intracarotid cisplatin for cytoreduction (not for mobilization). At 1 month after this CT, they were mobilized with 12 lg/kg filgrastim. The second group (22 patients) was mobilized with the same dose of filgrastim directly after the surgery, without having ever received any prior CT. The blood level of CD34þ cells was significantly lower in the CT-treated patients, both on the fourth day of filgrastim (15 vs 36 cells 106/l; P¼0.01) and on the fifth (25 vs 58 cells 106/l; P¼0.003), as it was the number of CD34þ cells collected per apheresis (1.3 vs 3.5 106/l; Po0.0005). The toxic effect of a single course of BCNUcisplatin CT led to significant impairment of the filgrastim-induced mobilization response. Bone Marrow Transplantation advance online
- Intraoperative radiotherapy electron boost followed by moderate doses of external beam radiotherapy in resected soft-tissue sarcoma of the extremities(Elsevier, 2003) Martinez-Monge, R. (Rafael); Aristu-Mendioroz, J.J. (José Javier); San-Julian, M. (Mikel); Calvo, F.A. (Felipe A.); Azinovic, I. (Ignacio); Salgado, E. (Esteban); Villafranca, E. (Elena); Aramendia, J.M. (J.M.); Amillo, S. (Santiago); Villas-Tome, C. (Carlos); Fernandez-Hidalgo, Ó. (Óscar)To analyze the patterns of failure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). PATIENTS AND METHODS: Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was >5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. RESULTS: Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P=0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P=0.01). CONCLUSIONS: IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage.
- Resultados a medio y largo plazo de la utilización de videotoracoscopia en la cirugía de resección de las metástasis pulmonares(Gobierno de Navarra. Departamento de Salud, 2005) Torre, W. (Wenceslao); Rodriguez-Spiteri, N. (Natalia); Lopez-Picazo, J.M. (José M.); Gurpide, A. (Alfonso); Villalobos, W. (W.); Fernandez-Hidalgo, Ó. (Óscar)The surgical resection of pulmonary metastases is a method of treatment accepted as habitual in thoracic surgery. However, it continues to be a source of controversy if this resection must be realised by thoracotomy or by modern video-assisted techniques. With the aim of finding a response to this controversy in our work milieu, a review was made of the surgical interventions carried out in order to resect pulmonary metastases. Between January 1997 and December 2001, 56 patients were found whose pulmonary metastases had been resected by videothorascopy out of a total of 252 metastasectomies (22.2%). The primary tumours were classified in 4 groups: sarcoma (n=11); colorectal (n=25); renal (n=5); and others (n=15). Videothoroscopy was carried out on the right hemithorax (n=28), left hemithorax (n=22) or on both at once (n=6). Operational mortality was nil and the only morbidity attributable to the technique was a defect of re-expansion following the removal of the thoracic drainage in one patient. Using the Kaplan-Meier method, the probability of survival in this series of patients was 60.4% after 5 years, with an average survival time of 48 months. All of this data supports the use of videothorascopy in our milieu on patients with pulmonary metastases. However, in the light of the results, it is important in using this technique to place special emphasis on obtaining good margins of resection, due to the real risk of local recurrence on these margins in the medium term.
- 120 hours simultaneous infusion of cisplatin and fluorouracil in metastatic breast cancer(Lippincott, Williams & Wilkins, 1989) Lacave, A.J. (A. J.); Campbell, W. (W.); Barrajon, E. (E.); Gil, A. (A.); Gonzalez, F. (Fidel); Fernandez-Hidalgo, Ó. (Óscar)Thirty-six patients with metastatic breast cancer, 23 with documented progression of the disease after first-line chemotherapy (CAF or CMF) and 13 without prior chemotherapy, were treated with a simultaneous 120-h infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU). Objective response was demonstrated in 19 patients (52.7%), stable disease in 7 patients (19.4%) and progression of the disease in 10 patients (27.7%). Similar response rate was observed according to tumor site (soft tissues, 50%; bone, 52%; lung, 63%; liver, 55%; and pleura and peritoneum, 42%) and previous treatment (previous chemotherapy, 48%; previously untreated, 61%). Median duration of response was 8 months. Toxicity was characterized by stomatitis and myelodepression and required dose adjustments in 30% of patients. CDDP and 5-FU infusion deserve further investigation because it appeared to have substantial activity in this preliminary study in metastatic breast cancer.