Nuestros investigadores

José Javier Aristu Mendioroz

Oncología Radioterápica
Clínica Universidad de Navarra. Clínica Universidad de Navarra

Publicaciones científicas más recientes (desde 2010)

Autores: Rodríguez Ruiz, María Esperanza; Garasa, S., ; Rodriguez, I., ; et al.
ISSN 0360-3016  Vol. 97  Nº 2  2017  págs. 389 - 400
Purpose/Objectives: The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Materials/Methods: Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGF beta in this process anti-TGF beta blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGF beta and /or anti-ICAM1 blocking mAb. Results: We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGF beta. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Conclusion: Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to immunotherapy. (C) 2016 Elsevier Inc. All rights reserved.
Autores: Inogés Sancho, Susana Inmaculada; Tejada Solís, Sonia; López Díaz de Cerio, Ascensión; et al.
ISSN 1479-5876  Vol. 15  Nº 1  2017  págs. 104-116
Our results suggest that the addition of tumor lysate-pulsed autologous DCs vaccination to tumor resection and combined radio-chemotherapy is feasible and safe. A multicenter randomized clinical trial is warranted to evaluate the potential survival benefit of this therapeutic approach. Trial registration This phase-II trial was registered as EudraCT: 2009-009879-35 and Identifier: NCT01006044 retrospectively registered.
Autores: Martínez-Vélez, N., ; Marigil Sánchez, Miguel; Aristu Mendioroz, José Javier; et al.
ISSN 1522-8517  Vol. 19  2017  págs. 28 - 28
Autores: Cambeiro Vázquez, Félix Mauricio; Martínez Regueira, Fernando; Rodríguez-Spiteri Sagredo, Natalia; et al.
ISSN 1538-4721  Vol. 15  Nº 4  2016  págs. 485 - 494
Purpose: To assess the safety, feasibility, and efficacy of free-hand intraoperative multicatheter breast implant (FHIOMBI) and perioperative high-dose-rate brachytherapy (PHDRBT) in early breast cancer. Methods and Materials: Patients with early breast cancer candidates for breast conservative surgery (BCS) were prospectively enrolled. Patients suitable for accelerated partial breast irradiation (APBI) (low or intermediate risk according GEC-ESTRO criteria) received PHDRBT (3.4 Gy BID × 10 in 5 days). Patients not suitable for APBI (high risk patients according GEC-ESTRO criteria) received PHDRBT boost (3.4 Gy BID × 4 in 2 days) followed by whole breast irradiation. Results: From June 2007 to November 2014, 119 patients were treated and 122 FHIOMBI procedures were performed. Median duration of FHIOMBI was 25 minutes. A median of eight catheters (range, 4-14) were used. No severe intraoperative complications were observed. Severe early postoperative complications (bleeding) were documented in 2 patients (1.6%), wound healing complications in 3 (2.4%), and infection (mastitis or abscess) in 2 (1.6%). PHDRBT was delivered as APBI in 88 cases (72.1%) and as a boost in 34 (27.8%). The median clinical target volume T was 40.8 cc (range, 12.3-160.5); median D90 was 3.32 Gy (range, 3.11-3.85); median dose homogeneity index was 0.72 (range, 0.48-0.82). With a median followup of 38.4 months (range, 8.7-98.7) no local, elsewhere, or regional relapses were observed; there was only one distant failure in PHDRBT boost. No major (acute or late) RTOG grade 3 or higher were documented in any of the 119 patients treated with PHDRBT. Cosmetic outcome in APBI patients was excellent or good in (87.0%) and fair or poor in (11.9%) while in boost patients was excellent or good in (76.4%) and fair in (23.5%). Conclusion: The FHIOMBI-PHDRBT program does not add complications to conservative surgery. It allows precise selection of APBI patients and offers excellent results in disease control and cosmetics. It also offers logistic advantages because it dramatically shortens the time of local treatment and avoids further invasive procedures.
Autores: Lopez Martin, J. A., ; de la Cruz Merino, L., ; Arance Fernandez, A. M., ; et al.
ISSN 0923-7534  Vol. 27  Nº Supl. 6  2016  págs. 1118P
Background: Estimated median overall survival (OS) in patients (pts) with brain metastases (BM) ranges between 1.8-10.5 months (mo). Ipilimumab (IPI) has shown activity against mel-BM. Radiation (RT) might be synergistic to anti-CTLA-4 blockade through an `abscopal¿ effect. Methods: Open label single stage multicenter phase 2 study, assuming a historical 20% 1-year survival rate (1y SR) with RT. Target sample size: 56 evaluable pts. Target 1y SR: 35% (¿= 0.05, ß= 0.2). Objectives: Primary: 1y SR; Secondary: progression free survival (PFS); OS; objective response rate (mWHO); safety and feasibility. Treatment: IPI 3 mg/Kg iv q 3 weeks (4 cycles); whole brain RT (WBRT) 30 Gy in 10 fractions (or equivalent), started between C1 and C2. Main eligibility: First episode of BM in mel pts; Karnofsky PS > 70%; Barthel Index > 10; RTOG-RPA class 2; measurable disease; LDH < 2 x ULN; not eligible for radical therapy; not experiencing rapid clinical deterioration; not requiring dexamethasone > 16 mg/d (or equivalent). Results: This is a preliminary analysis after recruiting 43/56 pts (Apr 2014 - Mar 2016). Demographical characteristics are shown in the table.
Autores: Martinez Velez, N., ; Marigil Sánchez, Miguel; Domínguez Echávarri, Pablo Daniel; et al.
ISSN 1522-8517  Vol. 18  Nº Supl.6  2016  págs. 61
Autores: Prieto Azcárate, Elena; Martí Climent, Josep María; Gómez Fernández, Marisol; et al.
ISSN 2222-3959  Vol. 33  Nº 2  2014  págs. 79 - 86
Objetivo Diseñar una técnica novedosa de adquisición ex-vivo para establecer un marco común de validación de diferentes técnicas de segmentación para imágenes PET oncológicas. Evaluar sobre estas imágenes el funcionamiento de varios algoritmos de segmentación automática. Material y métodos En 15 pacientes oncológicos se realizaron estudios PET ex-vivo de las piezas quirúrgicas extraídas durante la cirugía, previa inyección de 18F-FDG, adquiriéndose imágenes en 2 tomógrafos: un PET/CT clínico y un tomógrafo PET de alta resolución. Se determinó el volumen tumoral real en cada paciente, generándose una imagen de referencia para la segmentación de cada tumor. Las imágenes se segmentaron con 12 algoritmos automáticos y con un método estándar para PET (umbral relativo del 42%) y se evaluaron los resultados mediante parámetros cuantitativos. Resultados La segmentación de imágenes PET de piezas quirúrgicas ha demostrado que para imágenes PET de alta resolución 8 de las 12 técnicas de segmentación evaluadas superan al método estándar del 42%. Sin embargo, ninguno de los algoritmos superó al método estándar en las imágenes procedentes del PET/CT clínico. Debido al gran interés de este conjunto de imágenes PET, todos los estudios se han publicado a través de Internet con el fin de servir de marco común de validación y comparación de diferentes técnicas de segmentación. Conclusiones Se ha propuesto una técnica novedosa para validar técnicas de segmentación para imágenes PET oncológicas, adquiriéndose estudios ex-vivo de piezas quirúrgicas. Se ha demostrado la utilidad de este conjunto de imágenes PET mediante la evaluación de varios algoritmos automáticos.
Autores: Idoate Gastearena, Miguel Ángel; Echeveste, José Ignacio; Díez Valle, Ricardo; et al.
ISSN 0305-1846  Vol. 40  Nº 6  2014  págs. 736 - 746
AIMS: Glioblastomas display marked phenotypic and molecular heterogeneity. The expression of the PTEN protein in glioblastomas also shows great intratumour heterogeneity, but the significance of this heterogeneity has so far received little attention. METHODS: We conducted a comparative study on paraffin and frozen samples from 60 glioblastomas. Based on PTEN immunostaining, paraffin glioblastomas were divided into positive (homogeneous staining) and both positive and negative (heterogeneous staining) tumours. DNA was extracted from manually microdissected samples from representative areas, and from frozen samples taken randomly from the same tumours. Loss of heterozygosity (LOH) of 10q23 and hypermethylation status of the PTEN promoter were studied, and the molecular findings were correlated with overall survival. RESULTS: PTEN protein was present heterogeneously in 42 cases and homogeneously in 18 cases. In homogeneous glioblastomas, no correlation was found between PTEN protein expression and the LOH of the gene. Surprisingly, in the heterogeneous glioblastomas, LOH was found significantly more frequently (P < 0.001) in PTEN-positive areas (81%) than in PTEN-negative ones (35.7%). In general, molecular results of frozen tissue were representative of the tumour. Only two cases of methylation of the PTEN promoter were identified. A significant difference was found for overall survival for LOH10q23 status (P = 0.005) and for homogeneous vs. heterogeneous tumours (P = 0.014). CONCLUSION: The expression of PTEN protein does not correlate with the abnormalities of the LOH of the gene. Interestingly, patients with glioblastomas presenting either LOH of 10q23 or heterogeneous PTEN expression have a poorer prognosis.
Autores: Arbea Moreno, Leire; Martínez Monge, Rafael; Díaz González, Juan Antonio; et al.
ISSN 0360-3016  Vol. 83  Nº 2  2012  págs. 587-593
PURPOSE: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. RESULTS: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. CONCLUSIONS: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible
Autores: Gaztañaga Boronat, Miren; Pagola Divassón, María; Cambeiro Vázquez, Félix Mauricio; et al.
ISSN 1043-3074  Vol. 34  Nº 8  2012  págs. 1081-1088
Background This study aimed to test the safety of using perioperative high-dose-rate brachytherapy (PHDRB) in resected head and neck cancer. Methods From 2000 to 2008, 97 patients received PHDRB after complete macroscopic resection. Group 1 (previously irradiated patients) received 32 to 40 Gray (Gy) of PHDRB in 8 to 10 twice-daily (bid) treatments (R0R1 resections). Group 2 (unirradiated patients) received 16 to 24 Gy of PHDRB in 4 to 6 bid treatments (R0R1 resections) followed by external beam irradiation (EBRT) of 45 Gy/25 daily fractions +/- concomitant chemotherapy. Results The median follow-up was 4.3 years. The cumulative hazard of 2-year grade = 3 complications in group 1 was 45.9%, and the rate of grade = 3 complications in group 2 was 24.6%. Actuarial locoregional control at 2 and 5 years for group 1 was 60.9% and for group 2, 84.1% and 79.4%. Conclusions Complications and locoregional failure rates were similar to those reported in the reference standards despite a much smaller treatment volume. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2012
Autores: Bosch Barrera, Joaquim; García Franco, Carlos Enrique; Guillén Grima, Francisco; et al.
ISSN 1699-048X  Vol. 14  Nº 11  2012  págs. 835-41
The management of operable locally advanced N2 non-small cell lung cancer (NSCLC) is a controversial topic. Concurrent chemoradiation (CT-RT) is considered the standard of care for inoperable or unresectable patients, but the role of trimodality treatment remains controversial. We present our institution's experience with the management of stage III (N2) NSCLC patients, analyzing whether the addition of surgery improves survival when compared with definitive CT-RT alone. METHODS: From 1996 to 2006, 72 N2 NSCLC patients were treated. Thirty-four patients received cisplatin-based induction chemotherapy, followed by paclitaxel-cisplatin CT-RT, and 38 patients underwent surgery preceded by induction and/or followed by adjuvant therapy. Survival curves were estimated by Kaplan-Meier analysis, and the differences were assessed with the log-rank test. RESULTS: Most of the patients (87 %) were men. The median age was 59 years. A statistically significant association between T3-T4c and definitive CT-RT as well as between T1-T2c and surgery was noted (p < 0.0001). After a median follow-up period of 35 months, the median overall survival (OS) was 42 months for the surgery group versus 41 months for the CT-RT patients (p = 0.590). The median progression-free survival (PFS) was 14 months after surgery and 25 months after CT-RT (p = 0.933). Responders to radical CT-RT had a better OS than non-responders (43 vs. 17 months, respectively, p = 0.011). No significant differences were found in
Autores: Díez Valle, Ricardo; López Díaz de Cerio, Ascensión; Inogés Sancho, Susana Inmaculada; et al.
ISSN 2218-4333  Vol. 3  Nº 11  2012  págs. 142-149
Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-II study is ongoing to possibly improve further on our very encouraging clinical results.
Autores: Prieto Azcárate, Elena; Martí Climent, Josep María; Domínguez Prado, Inés; et al.
ISSN 0161-5505  Vol. 52  Nº 6  2011  págs. 865-72
Compared with standard (18)F-FDG PET studies, quantitative dual-time-point (18)F-FDG PET can improve sensitivity for the identification and volume delineation of high-grade brain tumors.
Autores: Gaztañaga Boronat, Miren; Aristu Mendioroz, José Javier; Villas Tomé, Carlos
ISSN 1867-4569  Vol. 1  Nº 5  2011  págs. 175 - 179
Background: Giant cell tumors (GCT) are relatively rare neoplasms, representing less than 5% of all bone tumors. They are most frequent in the extremities and are characterized by their local aggression. Treatment is typically surgery alone. Localization in the sacrum is rare, and here radiation therapy (RT) may be a useful tool for tumor management because of the difficulty of achieving accurate wide margins of surgical resection. We report a series of four cases treated by intralesional resection and RT. Patients and methods: From 1996 to 2007, four patients with histologically proven sacral giant cell tumors were treated with intentional intralesional surgery and RT in our institution. Three patients were female and one was male. Median age was 35.5 years (range 19-53). Results: After a median follow-up of more than 11 years (range 32-144 months), all the patients are alive and free of disease. Pain and neurological symptoms disappeared after treatment. No severe cases of acute or late toxicity have been reported. No radiological signs of progression were observed. Conclusion: We propose RT be considered as a standard coadjuvant treatment after intralesional surgery for sacral GCT, where efficient local control without severe toxicity is advisable.
Autores: Arbea Moreno, Leire; Díaz González, Juan Antonio; Subtil Íñigo, José Carlos; et al.
ISSN 0360-3016  Vol. 81  Nº 2  2011  págs. 439 - 444
Purpose: The main goals of preoperative chemoradiotherapy (CHRT) in rectal cancer are to achieve pathological response and to ensure tumor control with functional surgery when possible. Assessment of the concordance between clinical and pathological responses is necessary to make decisions regarding alternative conservative procedures. The present study evaluates the patterns of response after a preoperative CHRT regimen, and the value of endoscopic ultrasound (EUS) in assessing response. Methods and Materials: A total of 51 EUS-staged T3 to T4 and/or N0 to N+ rectal cancer patients received preoperative CHRT (intensity-modulated radiation therapy and capecitabine/oxaliplatin (XELOX) followed by radical resection. Clinical response was assesed by EUS. Rates of pathological tumor regression grade (TRG) and lymph node (LN) involvement were determined in the surgical specimen. Clinical and pathological responses were compared, and the accuracy of EUS in assessing response was calculated. Results: Twenty-four patients (45%) achieved a major pathological response (complete or >95% pathological response (TRG 3+/4)). Sensitivity, specificity, negative predictive value, and positive predictive value of EUS in predicting pathological T response after preoperative CHRT were 77.8%, 37.5%, 60%, and 58%, respectively. The EUS sensitivity, specificity, negative predictive value, and positive predictive value for nodal staging were 44%, 88%, 88%, and 44%, respectively. Furthermore, EUS after CHRT accurately predicted the absence of LN involvement in 7 of 7 patients (100%) with major pathological response of the primary tumor. Conclusion: Preoperative IMRT with concomitant XELOX induces favorable rates of major pathological response. EUS has a limited ability to predict primary tumor response after preoperative CHRT, but it is useful for accurately determining LN status. EUS may have a potential value in identifying patients with a very low risk of LN involvement in association with a good pathological response as potential candidates for conservative local surgical protocols. (C) 2011 Elsevier Inc.
Autores: Díaz González, Juan Antonio; Rodríguez Rodríguez, Javier; Hernández Lizoáin, José Luis; et al.
ISSN 0360-3016  Vol. 80  Nº 3  2011  págs. 698-704
PURPOSE: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. METHODS AND MATERIALS: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. RESULTS: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. CONCLUSIONS: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.
Autores: Pastor Idoate, Carlos; Subtil Íñigo, José Carlos; Sola Gallego, Jesús Javier; et al.
ISSN 0012-3706  Vol. 54  Nº 9  2011  págs. 1141 -6
Endoscopic ultrasound allows prediction of involved lymph nodes in 75% of the cases; however, 1 in 5 patients are missclassified as uN0 after neoadjuvant treatment. In our point of view, this percentage is too high to rely only on this diagnostic modality
Autores: Nieto Regueira, Yago Luis; Aramendía Beitia, José Manuel; Espinos Jiménez, Jaime; et al.
ISSN 0344-5704  Vol. 65  Nº 3  2010  págs. 457 - 465
Purpose Capecitabine is effective against metastatic breast cancer (MBC). We hypothesized that sequential treatment with dose-dense epirubicin/cyclophosphamide (EC) and docetaxel/capecitabine would be active and tolerable in the adjuvant/neoadjuvant setting. Methods In this prospective phase II clinical trial patients with HER2-negative and node-positive or locally advanced tumors were eligible to receive four cycles of EC (100/600 mg/m2) every 2 weeks with G-CSF on days 3¿10, followed by four cycles of docetaxel/capecitabine (75/1,000 mg/m2 b.i.d., days 1¿14) every 3 weeks. Results Fifty-five patients were enrolled with median age of 49, and 80% had hormone receptor-positive disease. The median tumor size was 2.5 cm, with a median of two axillary nodes involved. Seventy-five percent of the first 20 patients had grade 2/3 hand-foot syndrome (HFS). Dose reduction of capecitabine to 800 mg/m2 reduced the grade 2/3 HFS incidence to 31% in the remaining patients. No grade 4/5 toxicities were observed. All 20 patients treated preoperatively responded, with 5 (25%) pathologic complete responses and 3 additional pT0N1 tumors. At a median follow-up of 48 (range 28¿60) months, the event-free and overall survival rates are 91 and 98%, respectively. Conclusions Sequential treatment with dose-dense EC followed by docetaxel/capecitabine, using a lower capecitabine dose than that approved for MBC, has an acceptable toxicity profile and encouraging activity when used as neoadjuvant or adjuvant treatment of breast cancer.
Autores: Díez Valle, Ricardo; Tejada Solís, Sonia; Idoate Gastearena, Miguel Ángel; et al.
ISSN 0167-594X  Vol. 102  Nº 1  2010  págs. 105 - 113
We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM). Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin¿eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre- and postoperative volumetric magnetic resonance imaging. Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin¿eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%. The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor border.
Autores: Martínez Monge, Rafael; Gaztañaga Boronat, Miren; Aramendía Beitia, José Manuel; et al.
ISSN 1048-891X  Vol. 20  Nº 1  2010  págs. 133 - 140
Objectives: This study was undertaken to determine the tolerability of a 7-week schedule of external beam radiation therapy, high-dose-rate brachytherapy, and weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of the cervix. Methods: Twenty-nine patients with International Federation of Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40 mg/m2 per week of intravenous (i.v.) cisplatin and 50 mg/m2 per week of i.v. paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 30 Gy of high-dose-rate brachytherapy. Results: Eleven patients (37.9%) were able to complete the 6 scheduled cycles of chemotherapy. The median number of weekly chemotherapy cycles administered was 5 (range, 2-7). Thirty-five (20.1%) of 174 cycles of chemotherapy were not given because of toxicity. The median dose intensity of cisplatin was 31 mg/m2 per week (95% confidence interval [CI], 25.2-36.8); that of paclitaxel was 44 mg/m2 per week (95% CI, 39.9-48.3). Twenty-two patients (78.6%) were able to complete the planned radiation course in less than 7 weeks. Median radiation treatment length was 45 days (95% CI, 43.4-46.6). After a median follow-up of 48 months, 7 patients (24.1%) experienced severe (Radiation Therapy Oncology Group grade 3 or higher) late toxicity. No fatal events were observed. Seven patients have failed, 1 locally and 6 at distant sites. The 8-year local/pelvic control rate was 95.7%, and the 8-year freedom from systemic failure rate was 76.1%. Eight-year actuarial disease-free survival and overall survival were 63.1% and 75.9%, respectively. Conclusions: This study demonstrated unacceptable toxicity of combining the stated doses of concurrent cisplatin and paclitaxel chemotherapy with definitive radiotherapy for patients with advanced cervical cancer. Additional phase I/II trials are recommended to clearly establish the recommended phase II dose for these drugs.
Autores: Sola Gallego, Jesús Javier; Beorlegui Arteta, María Carmen; Panizo Santos, Ángel Fernando; et al.
ISSN 0893-3952  Vol. 23  Nº Supl.1  2010  págs. 168A