Impact of age on safety of Busulfan-Melphalan followed by autologous hematopoietic stem-cell transplantation versus standard chemotherapy in the patients of the EURO-E.W.I.N.G. 99 and Ewing 2008 clinical trials.

INTRODUCTION: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials. METHODS: We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models. RESULTS: The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group. CONCLUSION: The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.

Long term survival in adult osteosarcoma patients treated with a two-drug regimen: Final results of the OSAD93 phase II study of the FSG-GETO.

RATIONALE: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. PATIENTS AND METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. CONCLUSION: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.

Mesna, Doxorubicin, Ifosfamide and Dacarbazine (MAID) Combination Chemotherapy for Retroperitoneal Sarcoma: A Single-center Experience.

BACKGROUND/AIM: There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population. PATIENTS AND METHODS: We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized. RESULTS: At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm2 Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients. CONCLUSION: MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity.

Prolonged 14-day continuous infusion of high-dose ifosfamide for patients with relapsed and refractory high-grade osteosarcoma: a retrospective multicentre cohort study.

BACKGROUND: The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting. PATIENTS AND METHODS: The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5. RESULTS: The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities. CONCLUSIONS: 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.

Effectiveness and safety of primary prophylaxis with G-CSF for patients with Ewing sarcomas: a systematic review for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.

BACKGROUND: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?". METHODS: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain. RESULTS: Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval. CONCLUSION: This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.

A Rare Case of Methemoglobinemia after Ifosfamide Infusion in a 3-Year-Old Patient Treated for T-ALL.

Methemoglobinemia is a potentially life-threatening, rare condition in which the oxygen-carrying capacity of hemoglobin is diminished. We present the case of a 3-year-old boy treated for T-cell acute lymphoblastic leukemia (T-ALL) who developed methemoglobinemia (MetHb 57.1%) as a side effect of ifosfamide administration. Due to his critical condition, the patient was transferred to the intensive care unit (ICU). The therapy included methylene blue administration, an exchange transfusion, catecholamine infusion, and steroids. Improving the general condition allowed for continuing chemotherapy without ifosfamide and completion of the HR2 block. Vigilance for methemoglobinemia as a very rare side effect should be widespread when using ifosfamide in the treatment protocols.

Renal toxicity of ifosfamide in children with cancer: an exploratory study integrating aldehyde dehydrogenase enzymatic activity data and a wide-array urinary metabolomics approach.

BACKGROUND: Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity. METHODS: The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified. RESULTS: The 15 participants received a median total ifosfamide dose of 59 g/m2 (range: 24-102), given over a median of 7 cycles (range: 4-14). All children had acute proximal tubular toxicity during chemotherapy that was reversible post-cycle, seen with both conventional assays and NMR. After a median follow-up of 31 months, 8/13 children presented overall chronic toxicity among which 7 had decreased glomerular filtration rate. ALDH enzymatic activity showed high inter- and intra-individual variations across cycles, though overall activity looked lower in children who subsequently developed chronic nephrotoxicity. Concentrations of ifosfamide and metabolites were similar in all children. CONCLUSIONS: Acute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.

Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Ifosfamide-induced Fanconi syndrome with diabetes insipidus

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m2, a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.

Factores de riesgo ambientales no ocupacionales asociados al cáncer vesical / Environmental non-occupational risk factors associated with bladder cancer

Contexto: El carcinoma vesical (CV), por su elevada morbilidad y evolución recidivante, genera importantes costes asistenciales y económicos. Por ello revisaremos los factores de riesgo (FR) ambientales no ocupacionales implicados, con mayor o menor evidencia científica, en la etiopatogenia del CV, pues la implicación de los urológos es fundamental para su prevención. Adquisición de evidencia: Revisión bibliográfica de los últimos 25 años de los mencionados FR asociados al CV, obtenida de MedLine, Science Citation Index y Embase. Los perfiles de búsqueda han sido Risk Factors/Epidemiology/Tobacco-smoking/Diet-nutrition-water-liquids/Infectious/Radiation/Farmacological drugs y Bladder cancer. Síntesis de evidencia: El tabaquismo se asocia al 50% de los CV en ambos sexos. Los fumadores presentan riesgos 2-5 veces superiores, dependiendo de la intensidad y duración de la adicción. El agua potable contaminada con arsénico, subproductos de cloración y cromo, incrementa el riesgo de CV. Consumos altos de carne roja y grasa saturada posiblemente aumenten el riesgo, mientras la ingesta elevada de frutas y verduras lo disminuye. La administración de ciclofosfamida, ifosfamida y radioterapia incrementa el riesgo de CV. El uso frecuente y prolongado de tintes capilares y la infestación por Schistosoma haematobium se asocian a mayores riesgos. Conclusiones: La reducción o eliminación del tabaquismo disminuirá la prevalencia del CV. El consumo de agua sin contaminantes, con el incremento de alimentos vegetales favorece la prevención del CV. Los supervivientes de cánceres tratados con ciclofosfamida, ifosfamida y radioterapia deben ser monitorizados para el diagnóstico precoz del CV (AU)

Context: Bladder carcinoma (BC), due its high morbidity and relapsing course, generates significant economic and health care costs. Accordingly, review the environmental nonoccupational risk factors (RF), more or less evidence-based, in the etiology and pathogenesis of BC, because the involvement of urologists is essential for prevention. Acquisition of evidence: Review of the peer-reviewed literature (1987-2012) on nonoccupational environmental RF associated with BC retrieved from Medline, Embase and Science Citation Index. The search profiles have been «Risk factors/Epidemiology/Tobacco-smoking/Diet-nutrition-water-liquids/Radiation/Infectious/Farmacological drugs» and «Bladder cancer». Synthesis of evidence: Smoking was associated with 50% of BC in both sexes. Smokers have a 2-5 times higher risk than nonsmokers, directly proportional to the amount and duration of addiction. Drinking water contaminated with arsenic and chromium chlorination byproducts increases the risk of BC. High consumption of red meat and saturated fat may increase the risk, while high intake of fruits and vegetables decreases it. Patients treated with cyclophosphamide, ifosfamide and ionizing radiation have an increased risk of BC. Frequent and prolonged use of hair dyes and Schistosoma haematobium infestation increases the risk of BC. Conclusions: The reduction or the cessation of smoking decrease BC. The contaminant-free water consumption with the increase of vegetal foods favour BC prevention. Cancer survivors treated with cyclophosphamide, ifosfamide and radiation therapy should be monitored for early diagnosis of BC (AU)

Interleukin-11 attenuates ifosfamide-induced hemorrhagic cystitis

OBJECTIVE: To investigate the possible protective effect of recombinant human interleukin-11 (rhIL-11) against ifosfamide (IFS)-induced hemorrhagic cystitis (HC) MATERIALS AND METHODS: Male Swiss mice (20-30g) were pretreated with rhIL-11 (25-625 mg, subcutaneously.) 30 min before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Twelve hours later, HC was evaluated by bladder wet weight (BWW) to quantify edema, Evans blue extravasation (EBE) to measure vascular permeability, and macroscopic and microscopic analysis. All bladders were assessed by histopathological analysis RESULTS: rhIL-11 (at 125 and 625 mg) attenuated the IFS- induced increase of BWW (37.48 percent and 45.44 percent, respectively, p < 0.05) and EBE (62.35 percent and 56.47 percent, respectively, p < 0.05). IFS- induced macroscopic edema and hemorrhage and microscopic alterations, were also prevented by rhIL-11 at 625 mg. (p < 0.05) CONCLUSION: Our results demonstrate a protective effect of rhIL-11 on experimental IFS- induced HC, not previously reported.

Neurotoxicidad secundaria a ifosfamida consecutivamente en forma de psicosis y coma / No disponible

No disponible

Treatment and prophylaxis of ifosfamide-induced encephalopathy with intravenous methylene blue

No disponible

Emesis y citostáticos en el paciente pediátrico / Vomiting and cytostatic therapy in the pediatric patients

El objetivo de este estudio fue evaluar la seguridad y eficacia del ondansetron en niños con neoplasias malignas para prevenir la emesis inducida por agentes antineoplásicos con potentes efectos emetizantes. Se incluyeron 138 niños, 76 varones y 62 mujeres con tumores sólidos que cumplieron 415 ciclos de quimioterapia, desde octubre de 1993 a noviembre de 1994, en la Unidad de Administración de Citostáticos del Hospital de Pediatría "Prof. Dr. Juan P. Garrahan". Las edades oscilaron entre 1 y 17 años con una mediana de 8 para todos los grupos. Se analizaron tres tratamientos: Grupo A) 65 ciclos de quimioterapia con ifosfamida a dosis de 1.800 mg/m2/día (n=29); grupo B) 177 ciclos con ifosfamida a dosis de 3.000 mg/m2/día (n=54) y grupo C) 173 ciclos con cis-platino a dosis > 50 mg/m2/día (n=55). El antiemético utilizado fue el ondansetron a 5 mg/m2/dosis administrado por vía intravenosa cada 8 hs, durante todo el ciclo y hasta el egreso del paciente. Se obtuvo completo control de la emesis en el 69 por ciento de los ciclos en el grupo A; 54 por ciento en el grupo B y 70 por ciento en el grupo C. No se registraron reacciones adversas atribuibles al antiemético utilizado. Comparando los grupos A vs B (z: 2,225; P=0,026); B vs C (z: 3156; P=0,002), la diferencia fue significativa. En los grupos A vs C (z: 0,009; P=0,993), la diferencia no fue significativa. Conclusiones: Si bien el ondansetron resultó ser un antiemético seguro y eficaz en el control de las néuseas y vómitos agudos durante la quimioterapia, la respuesta fue menor en protocolos que incluyeron ifosfamida a 3.000 mg/m2/día, diferencia estadísticamente significativa con los otros dos grupos analizados. La dosis de este citostático influyó en la respuesta antiemética del ondansetron. Sugerimos, en función de los resultados del presente trabajo, modificar el esquema antiemético en protocolos con ifosfamida a 3.000 mg/m2/día o tal vez, prolongar la infusión de este citostático

Emesis y citostáticos en el paciente pediátrico / Vomiting and cytostatic therapy in the pediatric patients

El objetivo de este estudio fue evaluar la seguridad y eficacia del ondansetron en niños con neoplasias malignas para prevenir la emesis inducida por agentes antineoplásicos con potentes efectos emetizantes. Se incluyeron 138 niños, 76 varones y 62 mujeres con tumores sólidos que cumplieron 415 ciclos de quimioterapia, desde octubre de 1993 a noviembre de 1994, en la Unidad de Administración de Citostáticos del Hospital de Pediatría "Prof. Dr. Juan P. Garrahan". Las edades oscilaron entre 1 y 17 años con una mediana de 8 para todos los grupos. Se analizaron tres tratamientos: Grupo A) 65 ciclos de quimioterapia con ifosfamida a dosis de 1.800 mg/m2/día (n=29); grupo B) 177 ciclos con ifosfamida a dosis de 3.000 mg/m2/día (n=54) y grupo C) 173 ciclos con cis-platino a dosis > 50 mg/m2/día (n=55). El antiemético utilizado fue el ondansetron a 5 mg/m2/dosis administrado por vía intravenosa cada 8 hs, durante todo el ciclo y hasta el egreso del paciente. Se obtuvo completo control de la emesis en el 69 por ciento de los ciclos en el grupo A; 54 por ciento en el grupo B y 70 por ciento en el grupo C. No se registraron reacciones adversas atribuibles al antiemético utilizado. Comparando los grupos A vs B (z: 2,225; P=0,026); B vs C (z: 3156; P=0,002), la diferencia fue significativa. En los grupos A vs C (z: 0,009; P=0,993), la diferencia no fue significativa. Conclusiones: Si bien el ondansetron resultó ser un antiemético seguro y eficaz en el control de las néuseas y vómitos agudos durante la quimioterapia, la respuesta fue menor en protocolos que incluyeron ifosfamida a 3.000 mg/m2/día, diferencia estadísticamente significativa con los otros dos grupos analizados. La dosis de este citostático influyó en la respuesta antiemética del ondansetron. Sugerimos, en función de los resultados del presente trabajo, modificar el esquema antiemético en protocolos con ifosfamida a 3.000 mg/m2/día o tal vez, prolongar la infusión de este citostático (AU)

Tratamiento del cancer de protasta avanzado hormonoresistente con difosfato de dietiletilbestrol (DES-P) e ifosfamida-mesna: estudio en fase II / Treatment of hormone resistant advanced prostatic neoplasm with diethylstilbestrol diphosphate (DES-P) and iphosfamide-mesna: phase II study

El empleo de dietiletilbestrol difosfato ha sido exitoso para el tratamiento del carcinoma de prostata hormonoresistente. En 44 pacientes con enfermedad medible con centelleograma oseo patológico, un índice medio de Karnofsky de 50 (rango 30-90), edad media 66 años (rango 46-79) y todos tratados previamente con estrógenos, fueron tratados con DES-P o con DES-P más IF/Mesna. Las características clínicas y de laboratorio previas al tratamiento, eran comparables. DES-P se administró a razón de 800 mg/m en infusión iv de 24 horas, disuelto en sol, destrosa 5% 1500 ml, durante 7 días consecutivos. El ciclo se repitió cada 28 días. En el plan con DES-P más IF/Mesna, DES-P se administró con igual metodología; IF/Mesna 5g/m en infusión iv de 24 horas, disuelto en 2000 ml de sol, dextrosa 5%, el día 8§. Los ciclos se repitieron cada 28 días. Se requirieron 2 ciclos para evaluar respuesta, de acuerdo al criterio del Proyecto Nacional de Cáncer de Prostata de los EEUU. La toxicidad hematológica fué leve; se observó hematuria microscópica en 3, y síntomas del SNC en 2 pacientes. El porcentaje de respuesta fué similar con ambos tratamientos, pero el tiempo medio de pregresión y la sobrevida, fueron significativamente superiores con DES-P ñ IF/Mesna