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)

Síndrome de Fanconi por agentes quimioterapéuticos: serie de casos y revisión de la literatura

Introducción: múltiples agentes quimioterapéuticos que se usan comúnmente pueden causar síndrome de Fanconi (SF) completo o parcial. El SF es una tubulopatía proximal que produce alteraciones electrolíticas y ácido-básicas, donde se evidencia pérdida de glucosa, aminoácidos, calcio, fósforo, potasio, ácido úrico y se produce acidosis metabólica por pérdida de bicarbonato. El SF usualmente no es reportado y muchas veces no se realiza el diagnóstico. Objetivo: resaltar la importancia del monitoreo urinario y sérico en pacientes que estén sometidos a quimioterapia, así como describir la literatura reciente acerca de la asociación entre agentes quimioterapéuticos y síndrome de Fanconi parcial o completo. Presentación de los casos: se presenta una serie de casos de pacientes pediátricos oncológicos con función renal preservada, donde se produjeron diferentes manifestaciones de nefrotoxicidad tubular proximal secundaria a agentes quimioterapéuticos como antimetabolitos, agentes alquilantes y antraciclinas. Discusión y conclusión: el espectro del SF puede ir de una tubulopatía proximal generalizada o completa a alteraciones parciales en la reabsorción de electrolitos. Se debe reconocer la importancia del monitoreo sérico y urinario en pacientes con lesiones tumorales que van a ser sometidos a quimioterapias con agentes potencialmente nefrotóxicos; asimismo, tener en cuenta la dosis, la frecuencia y la combinación de agentes quimioterapéuticos, con el fin de prevenir y tratar complicaciones de toxicidad renal, incluyendo SF completo o parcial.

Introduction: Several commonly used chemotherapeutic agents can cause complete or partial Fanconi syndrome (FS). FS is a proximal tubulopathy that produces electrolyte and acid base disorders where there is loss of glucose, amino acids, calcium, phosphorus, potassium, uric acid and metabolic acidosis occurs due to loss of bicarbonate. FS is not usually reported, and the diagnosis is often misled. Purpose: To highlight the importance of urinary and serum monitoring in patients undergoing chemotherapy, as well as describe the recent literature about the association between chemotherapeutic agents and partial or complete Fanconi syndrome. Case presentation: A series of cases of pediatric oncology patients with preserved renal function is presented in which different manifestations of proximal tubular nephrotoxicity occurred secondary to chemotherapeutic agents such as antimetabolites, alkylating agents, and anthracyclines. Discussion and conclusion: The spectrum of FS can range from a generalized or complete proximal tubulopathy to partial alterations in electrolyte reabsorption. The importance of serum and urinary monitoring should be recognized in patients with tumor lesions who will undergo chemotherapies with potentially nephrotoxic agents; the dosage, frequency and combination of chemotherapeutic agents should be taken into account, in order to prevent and treat the complications of renal toxicity including complete or partial SF.

Bloqueio do receptor da interleucina-1 com anakinra inibe a cistite hemorrágica induzida por ifosfamida

Cistite hemorrágica (CH) induzida por ifosfamida (IFO) é uma importante complicação clínica em pacientes com câncer. Atualmente, mesna e hiper-hidratação são utilizadas como profilaxia, a despeito de ainda ser observada CH através de cistoscopia e histopatologia mesmo com essas medidas. A participação de interleucina-1 (IL-1) e fator de necrose tumoral (TNF) na patogênese da CH provê alvos para o tratamento dessa doença. Assim, esse trabalho objetivou avaliar o efeito protetor do antagonista do receptor da IL-1 (anakinra) e do anticorpo anti-TNF-alfa (infliximabe) nas respostas inflamatórias, nociceptivas e funcionais da CH experimental induzida por IFO em camundongos. Foram utilizados camundongos Swiss, C57BL6, IL-1R-/-, CASP1-/-, TNFR1-/-, TNFR1/R2-/-. Os animais WT foram submetidos ao tratamento com anakinra 100 mg/kg i.p. ou infliximabe 5 mg/kgi.p. ou salina i.p., foram tratados 1h após com IFO 400 mg/kg i.p., e 12 h após a IFO foi realizado o sacrifício, com excisão das bexigas para avaliaçãomacroscópica, histopatológica, permeabilidade vascular, mieloperoxidase, contratilidade, cistometrografia e citometria de fluxo para neutrófilos e macrófagos. Alguns animais, antes do sacrifício, foram submetidos a avaliação de nocicepção visceral. Anakinra foi capaz de atenuar hemorragia, edema, infiltrado neutrofílico, hipernocicepção visceral e disfunção vesical...

Hemorrhagic cystitis (HC) induced by ifosfamide (IFO) is an importantclinical complication in patients with cancer. Despite prophylaxis, HC isobserved. The role of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in the pathogenesis of HC provides targets for treatment. Thus, this study aimed to evaluate the protective effect of the IL-1 receptor antagonist (anakinra) and anti-TNF-alpha antibody (infliximab) in experimental HC-induced by IFO in mice. Swiss , C57BL6 , IL -1R-/-, CASP1-/-, TNFR1-/-, TNFR1/R2-/-mice were used. Animals were submitted to pre-treatment with anakinra 100 mg/ kg, ip or infliximab 5 mg/ Kg, ip, or saline ip, 1h after, they were treated with IFO 400 mg/ kg ip, and 12 h after IFO injection they were killed. Then, it was performed resection of the bladder for macroscopic and histopathological evaluation, vascular permeability assay, myeloperoxidase assay, muscle contractility, cistometrogram and flow cytometry to neutrophils andmacrophages. Some animals prior to death, were subjected to evaluation of visceral nociception. Anakinra was able to attenuate hemorrhage, edema, neutrophil infiltration, visceral hypernociception and bladder dysfunction...

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.

Clinical therapeutic efficacy analysis of the optimized neo-adjuvant chemotherapy protocols in the treatment of osteosarcoma / 中国医师杂志

Objective To investigate the efficacy and side effects of new combination of high-dose methotrexate (MTX),cisplatin (DDP),pirarubicin (THP),and ifosfamide (IFO) in the treatment of extremity osteosarcoma patients.Methods A retrospective analysis was conducted for 125 osteosarcoma patients treated with the optimized neo-adjuvant chemotherapy combined with the four drugs mentioned above (MTX 200 mg/kg iv 6 h d1,CF 9 mg at one time,12 times; DDP 100 mg/m2,THP 30 mg iv,d8-10;IFO 3.0 g/m2 iv d16-18,mesna after IFO for 0,3,6,9 h).The efficacy and side effects of the therapeutic scheme were evaluated.Results The effective salvage rates of Ⅱ a and Ⅱb schemes were 36.4％ (8/22) and 79.6％ (82/103) with a statistical significance (P ＜ 0.05).The 2-year survival rate of schemes was 62.4％,and the survival time was(17.7 ± 8.3)months.The main side effects were myelo-suppression,nausea,and vomiting,etc.The incidence rate of myelo-suppression,nausea,and vomiting with grade Ⅲ-Ⅳ accounted for 71.2％,37.6％,and 13.6％,respectively.Conclusions The optimized neo-adjuvant therapy strategy based on high-dose MTX,DDP,THP,and IFO is effective in the treatment of osteosarcoma.

High-dose tamoxifen plus ifosfamide and anthracycline in a patient with angiosarcoma of the breast / Tamoxifen en dosis alta con ifosfamida y antraciclina en un paciente con angiosarcoma de mama

Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas ofthe breast.

Aunque el cáncer de mama, desafortunadamente, no es poco común en las mujeres, apenas 0.04% de los tumores malignos de mama son angiosarcomas primarios. La quimioterapia es el tratamiento de preferencia en los casos de angiosarcomas de mama. Sin embargo, no existen guías en relación con los protocolos o la quimioterapia óptima. En la actualidad, el pronóstico para los angiosarcomas de mama es pobre. Este informe del caso describe a una mujer de 24 años diagnosticada con angiosarcoma primario de mama. Inicialmente la paciente se negó a recibir tratamiento, pero volvió al hospital cuatro años más tarde con un hemoneumotórax. Fue tratada entonces con quimioterapia de rescate usando una combinación de alta dosis de tamoxifen con ifosfamida y epirrubicina (antraciclina). Llegó a responder parcialmente al tratamiento, pero falleció 16 meses después del inicio de la terapia. Se necesitan más investigaciones para elaborar nuevos quimioterápeuticos y protocolos que mejoren los resultados en los casos de mujeres diagnosticadas con angiosarcomas primarios de mama.

Fatal Ifosfamide-Induced Metabolic Encephalopathy in Patients with Recurrent Epithelial Ovarian Cancer: Report of Two Cases / Journal of the Korean Cancer Association, 대한암학회지

Central nervous system (CNS) toxicity has been reported in approximately 10-30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Although methylene blue can be used to treat ifosfamide-induced neurotoxicity, including encephalopathy, its mechanism of action remains poorly defined. We describe here two patients with recurrent epithelial ovarian cancer who experienced fatal encephalopathy following ifosfamide/mesna treatment.

Effects of bortezomib combined with ifosfamide, methylprednisolone and thalidomide for the treatment of multiple myeloma / 白血病·淋巴瘤

Objective To investigate the efficacy and toxicity of bortezomib in combination with ifosfamide, methylprednisolone, thalidomide (V-CMPT) for the treatment of multiple myeloma (MM). Methods Twenty-four patients with newly diagnosed or relapsed/refractory MM were treated with V-CMPT. This regimen was repeated every three weeks as one cycle, and each case received two cycles. We adopted the examination of bone marrow and M protein and other hematological markers to evaluate the condition of disease and the therapeutic response. Results Of the nine patients with newly diagnosed MM, three achieved a complete remission (CR), five of a partial response (PR), and 1 of a minor response (MR). Of the patients with relapsed/refractory MM, two achieved a CR, two had a near CR (nCR), three had a PR, six had a MR, and two were no chang (NC). There was no obvious difference in the two groups (P = 0.511, P = 1.000). The overall response rate (ORR) was 91.7 %, and the CR/nCR rate was 29.2 %. After two cycles, the levels of hemoglobin, the serum albumin and the serum β2-microglobulin were obviously improved. The main adverse events were transient, including gastrointestinal reaction, thrombocytopenia, neuropathy, which could be controlled during the interval of chemotherapy or by symptomatic treatment and had no influence on the chemotherapy.Conclusion V-CMPT regiman was effective against the newly diagnosed and relapsed/refractory MM and could improve the related hematological markers with high response rate and tolerable toxicities.

Gemcitabine based combination chemotherapy, a new salvage regimen for recurrent platinum resistant epithelial ovarian cancer / 中华妇产科杂志

Objective To evaluate the efficacy and toxicities of gemcitabine combined with ifosfamide and anthracycline chemotherapy for recurrent platinum resistant ovarian epithelial cancer.Methods Gemcitabine 800 mg/m2 ( day 1, 8 ), ifosfamide 1.5 g/m2 ( day 1 - 3 ), adriamycin 40 mg/m2 or epirubicin 60 mg/m2 (day 1 ) or mitoxantrone 10 mg/m2 (day 1, 8 ) were used in recurrent platinum resistant/refractory ovarian cancer patients, the cycle was repeated at interval of 21 to 28 days.Results A total of 60 patients received 172 cycles combined chemotherapy.There were no one cases complete response, while partial response 22 (37%, 22/60), stable 23 (38%, 23/60) and progression 15 (25%,15/60) were observed, with clinical benefit rate 75% (45/60).The median time of progression-free survival was 7 months, and the median overall survival time was 20 months.The main side effect was hematologic toxicity with leukopenia rate of 82% (49/60), among which Ⅲ - Ⅳ accounted for 31%(15/49).Digestive reaction was all in Ⅰ - Ⅱ , accounted for 42% (25/60).Conclusion The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.

The effects of combination of ifosfamide,nedaplatin and pharmorubicin in treatment of relapsed ovarian carcinoma / 中国基层医药

Objective To investigate the treatment effectsand safety of ifosfamide,nedaplatin with pharmorubicin in relapsed ovarian carcinoma.Methods Sixteen relapsed ovarian carcinoma patients received nedaplatin 150mg in 0.9% sodium chloride 500ml dl,intravenously;pharmorubicin 40mg in 5% glucose 50 ml d1-2,intravenously;and ffosfamide 2.0g in 0.9% sodium chloride 500ml d1-5,intravenously.And the treatment effects and side effects were investigated.Results Of the sixteen patients,one had a complete response,six had a partial response,seven had stable disease,and two had progressive disease.The overall response rate was 43.75%(7/16).The major side effects were bone marrow suppression and gastrointestinal reaction.Conclusion Combination of ffosfamide,nedaplatin and pharmorubicin were very effective in relapsed ovarian carcinoma and the side effects were tolerable.Therefore the regimen is worth promoting in the clinical application.

Reversible Proximal Renal Tubular Dysfunction after One-Time Ifosfamide Exposure / Journal of the Korean Cancer Association, 대한암학회지

The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient experienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi's syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo adverse drug reaction probability scale indicated these complications were most likely treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity merits future investigation.

Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats

Ischemic preconditioning (IPC), a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g) models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8) were submitted to right or left paw edema (PE) with carrageenan (100 µg) or Dextran (200 µg), hemorrhagic cystitis with ifosfamide (200 mg/kg, ip) or gastric injury (GI) with indomethacin (20 mg/kg, vo). Controls received similar treatments, without IPC (Sham-IPC). PE is reported as variation of paw volume (mL), vesical edema (VE) as vesical wet weight (mg), vascular permeability (VP) with Evans blue extravasation (µg), GI with the gastric lesion index (GLI; total length of all erosions, mm), and neutrophil migration (NM) from myeloperoxidase activity. The statistical significance (P < 0.05) was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7 percent). IPC inhibited VE (38.8 percent) and VP (54 percent) in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3 percent; NM: 64 percent). This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.

Phase II study of concurrent cisplatinum with ifosfamide and radiotherapy in locally advanced squamous cell cervical carcinoma.

Objective: To evaluate the efficacy and toxicities of cisplatinum and ifosfamide administered concomitantly with radiation therapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods: Twenty patients with biopsy-proven squamous cervical carcinoma, FIGO stage II A to III B were entered into this study. All patients received standard radiotherapy (50 Gy in 25 fractions and brachytherapy at a dose of 268-28 Gy). Cisplatinum 70 mg/m2 plus ifosfamide 3 gm/m2 were administered totally for three cycles on Day 1, 21 and 42, concomitant with the radiotherapy schedule. Response and toxicities of treatment were evaluated and long term follow up was performed for disease free survival. Results: All patients received a course of concomitant chemoradiotherapy. Sixteen patients (80%) were able to receive a full course of chemotherapy, the remaining received 1-2 courses because of severe toxicities. The clinical complete response rate was 90% and overall 4 years survival rate was 85%. Grade 3 and 4 leucopenia occurred in 2 cases with one febrile neutropenia. Late complication revealed 2 cases of grade 3 cystitis. Conclusion: This study showed that concomitant chemoradiotherapy with cisplatinum plus ifosfamide was feasible for patients with LASCC. Further study of this regimen should be compared in randomized control trial (RCT) with cisplatinum alone and in the other histologic type of cervical cancer such as adenocarcinoma.

Phase II Study of Combination Chemotherapy with Etoposide and Ifosfamide in Patients with Heavily Pretreated Recurrent or Persistent Epithelial Ovarian Cancer

The aim of this trial was to investigate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of heavily pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with recurrent or persistent EOC who had measurable disease and at least two prior chemotherapy participating in this phase II trial were to receive etoposide at a dose of 100 mg/m2/day intravenously (IV) on days 1 to 3 in combination with ifosfamide 1 g/m2/day IV on days 1 to 5, every 21 days. Thirty-seven patients were treated; about 78% had previously received more than two separate regimens. The response rate (RR) was 18.9% and median duration of response was 7 months (range, 1-15). Treatment free interval prior to ETI (TFI) has significant correlation with RR rate (P=0.034). Patients (n=6) with TFI > or =6 months had 50% of RR, while patients (n=31) with TFI or =6 months.

Phase II Study of Vinorelbine Plus Ifosfamide in Patients with Taxane-resistant Metastatic Breast Cancer / 한국유방암학회지

PURPOSE: The patients with metastatic breast cancer are routinely exposed to taxane and anthracycline as neoadjuvant, adjuvant, and palliative chemotherapeutic agents. This study was designed to evaluate the efficacy and safety of using a vinorelbine and ifosfamide (VI) combination treatment in patients with taxane-resistant metastatic breast cancer. METHODS: We evaluated the use of a VI regimen (25 mg/m2 vinorelbine administered on days 1 and 8 plus 2,000 mg/m2 ifosfamide administered on day 1-3 every 3 weeks) for breast cancer patients who evidenced tumor progression after palliative taxane treatment. RESULTS: Overall, 35 patients were enrolled in this study: Their median age was 50 years (range, 38-72 years). The overall response rate was 40.0% (14 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 4.5 months (95% CI, 3.5-5.4 months). The median overall survival was 18.3 months (95% CI, 12.9-23.6 months). In the 190 cycle of treatment, the incidence of grade > or =3 neutropenia, anemia, and thrombocytopenia was 29.3%, 4.2%, and 2.0%, respectively. Neutropenic fever was noted in 6 cycles (3.1%). The non-hematological toxicities were not severe: grade 1 or 2 vomiting was observed in 22.8% of the patients. CONCLUSION: Our results suggest that the use of vinorelbine and ifosfamide (VI) combination chemotherapy appears to be effective and it showed an acceptable toxicity profile in the patients with taxane-resistant metastatic breast cancer.

Efficacy and tolerability of the combination of oxaliplatin, ifosfamide, and epirubicin in treatment of recurrent or platinum-resistant ovarian epithelial cancer patients / 中华妇产科杂志

Objective To evaluate the efficacy and tolerability of the combination of oxaliplatin,ifosfamide and epirubicin(IAP)in treatment of recurrent or platinum-resistant ovarian cancer patients.Methods A total of 25 patients received the combined chemotherapy of ifosfamide(3-4 g/m2),epirubicin(50-60 mg/m2)and oxaliplatin(130 mg/m2).The cycles were repeated every 21 days.The efficacy and toxicity were evaluated in 21 patients who received more than 2 cycles of IAP chemotherapy.Results The overall response rate was 71%,with a complete response in 10(48%),partial response in 5(24%),stable disease in one(5%),and disease progression in 5(24%).The median progression-free and overall survival time were 11(1 to 33)months and 31(1 to 71)months.While overall response rate was 60%in 10 patients with primary platinum resistant,and 88%in 8 patients with secondary platinumresistant.Grade Ⅲ-Ⅳ myelosuppression rate wss 30%.The most common non-hematologic toxicity was perineurotoxicity(38%).Conclusions The combination of oxaliplatin,ifasfamide and epirubicin appears to be effective for recurrent or platinum-resistant ovarian cancer patients as salvage chemotherapy and the toxicity is also tolerable.However,it needs to be evaluated by multiple clinical trials.

Selective Proximal Tubule Injury and Progressive Renal Failure due to Ifosfamide and Cisplatin in a Patient with Ovarian Cancer / 대한신장학회지

Ifosfamide-induced nephrotoxicity is usually manifested in the form of Fanconi syndrome and the combination of cisplatin enhances ifosfamide-induced nephrotoxicity. We here report a case of report specific proximal tubular dysfunction and progressive renal failure after ifosfamide and cisplatin chemotherapy in a 32-year old woman with ovarian cancer. The patient was referred to our department due to severe hypokalemia and elevated serum creatinine. Her renal function was abruptly impaired and serum and urine electrolytes were consistent with Fanconi syndrome. The kidney biopsy revealed atrophy and falling of renal tubular cells, and immunohistochemical staining with aquaporin 1 (AQP1) revealed that injured epithelial cells were proximal tubular cells. This finding suggests that ifosfamide selectively impairs proximal tubule function and combination with cisplatin causes progressive renal failure

Gemcitabina e ifosfamida no tratamento do linfoma de Hodgkin refratário ou recidivado após múltiplas terapias: [carta ao editor] / Gemcitabine and ifosfamide in the treatment of Hodgkin's lymphoma refractory to or relapsed after multiple therapies: [letter to the editor]

Patients with Hodgkin's lymphoma relapsed after or refractory to multiple therapies (rHL) have a dismal prognosis. Monotherapy with gemcitabine can promote an overall response rate of about 40 percent in these patients and its association with alkylating agents can provide better results. We retrospectively evaluated 17 rHL cases. All were treated with the combination of gemcitabine (1.0 g/m²; D1 and D8) and ifosfamide (1.0 g/m²; D1 to D5) in a 21-day cycle. Treatment response was evaluated according to the Cotswolds criteria. Toxicity was evaluated according to WHO criteria. The median age of all patients was 34 years (18-53). Nine of them (53 percent) were men and eight (47 percent) had Stage III/IV. The median number of previous treatments was 2 (2-3); two patients had already been treated with autologous stem cell transplant. Overall response rate to the combined regimen was 62.5 percent (95 percent CI = 38.8 percent - 86.2 percent) and the median progression-free survival was 15 months (95 percent CI = 4 - 24 months). Fifty-six cycles were evaluated for toxicity. The most frequent toxicities observed by cycle were: hepatic Grade I/II in 48.2 percent of the cycles and Grade III/IV in 1.8 percent; anemia Grade I/II in 45 percent; neutropenia Grade I/II in 36 percent and Grade III/IV 16 percent. Grade III/IV renal toxicity on any degree of haematuria were not observed. Combined therapy with Gemcitabine and Ifosfamide promoted responses in more than half of the evaluated patients with an acceptable toxicity profile.

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.

A phase II study of etoposide (VP-16), ifosfamide, and carboplatin combination chemotherapy plus concurrent thoracic irradiation for limited stage small cell lung cancer / 대한내과학회지

BACKGROUND: Small cell lung cancer (SCLC) is very sensitive to both chemotherapy and radiation therapy. In limited disease of SCLC, the addition of radiation therapy to chemotherapy improves survival and decrease local relapse over chemotherapy alone. This study evaluated the response rate, duration of response, overall survival and toxicity for the combination of etoposide, ifosfamide, carboplatin given concurrently with thoracic irradiation in limited SCLC. METHODS: Twenty eight patients with histologically proven SCLC who have a measurable disease and previously untreated, were enrolled in this study. Each cycle consisted of VP-16 100 mg/m2 IV days 1~3, ifosfamide 1,200 mg/m2 IV days 1~3 with mesna, carboplatin AUC 6 IV day 1. Cycles were repeated every 21days. Patients received a total of median 6,000 cGy thoracic radiation therapy (180~200 cGy/day) starting on the first day of chemotherapy. Prophylactic cranial irradiation was given to complete remission after chemoradiotherapy. RESULTS: The overall response rate in 27 evaluable patients was 93% (41% of complete response, 52% of partial response). The median time to progression was 10.3 months. The median disease free survival was 18.4 months in patients with complete response. The median overall survival was 16.7 months in all evaluable patients. Hematologic toxicities (> or = Grade3) of 129 cycles of chemotherapy were leukopenia in 38% and fever with infection in 26%. Nonhematologic toxicities (> or = Grade2) of evaluable 27 patients included alopecia in 11%, post-irradiation esophagitis in 44% and pneumonitis in 11%. CONCLUSIONS: VIC combination chemotherapy with concurrent thoracic irradiation is effective in limited SCLC. It's maior toxicity is myelosuppression.