Ifosfamid je protinádorový lék ze skupiny alkylačních cytostatik, jenž zabudováním alkylové skupiny do řetězce DNA naruší replikaci nukleotidových řetězců. Jedná se sice již o historický medikament, jehož vznik se datuje do 70. let minulého století, ale stále se s ním běžně setkáváme v onkologické praxi, např. u nádorů kostí, sarkomů měkkých tkání, ale i recidivujících nonhodgkinských lymfomů či lymfomů CNS. Tato terapie je zatížena řadou nežádoucích účinků, z nichž ke klasickým akutním nežádoucím účinkům patří reverzibilní encefalopatie a hemoragická cystitida. V této kazuistice z německé kliniky bych se rád zaměřil na renální toxicitu ifosfamidu, respektive poškození proximálního tubulu, v jehož důsledku se může rozvinout až tzv. Fanconiho synrom.

Ifosfamide is an anticancer drug from the group of alkylating cytostatics that disrupts the replication of nucleotide chains by incorporating an alkyl group into the DNA chain. Although it is a historical drug dating back to the 1970s, it is still commonly encountered in cancer treatment, e. g. in bone tumours, sarcomas and recurrent non-Hodgkin's lymphomas or CNS lymphomas. This therapy is burdened with a number of adverse effects, of the classic acute side effects include reversible encephalopathy and hemorrhagic cystitis. In this case report, I would like to focus on the renal toxicity of ifosfamide or damage to the proximal tubule, which may result in the development of Fanconi syndrome.

• MeSH
• Acidosis chemically induced   etiology   MeSH
• Adult MeSH
• Etoposide administration & dosage   adverse effects   MeSH
• Sarcoma, Ewing * diagnostic imaging   drug therapy   complications   physiopathology   MeSH
• Fanconi Syndrome * chemically induced   pathology   MeSH
• Ifosfamide administration & dosage   adverse effects   MeSH
• Drug Therapy, Combination methods   MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

BACKGROUND: The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA-RMS). PATIENTS AND METHODS: Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA-RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event-free survival (EFS) and overall survival (OS). RESULTS: From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non-bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5-81.6) and 93.5% (95% CI, 90.1-95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5-year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/- radiotherapy was not significant (p = 0.8003). Adjuvant radiotherapy improved EFS with 5-year estimates of 84.7% versus 65.2% for nonirradiated (p < .0001), but not OS (p = .9298). Omitting radiotherapy for orbital tumors reduced OS (5-year was 87.1% vs. 97.3% for irradiated, p = .0257). Following R0 resection (n = 60), radiotherapy did not significantly improve EFS or OS. CONCLUSIONS: Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS.

• MeSH
• Dactinomycin * administration & dosage   therapeutic use   MeSH
• Child MeSH
• Ifosfamide * administration & dosage   MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Child, Preschool MeSH
• Prospective Studies MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   MeSH
• Rhabdomyosarcoma * radiotherapy   therapy   mortality   surgery   drug therapy   MeSH
• Vincristine * administration & dosage   therapeutic use   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Europe MeSH

• MeSH
• Ifosfamide * pharmacology   adverse effects   therapeutic use   MeSH
• Humans MeSH
• Brain Diseases, Metabolic * diagnosis   etiology   classification   prevention & control   MeSH
• Methylene Blue administration & dosage   pharmacology   therapeutic use   MeSH
• Brain Diseases chemically induced   classification   MeSH
• Practice Guidelines as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade ≥3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272).

• MeSH
• Lymphoma, Large B-Cell, Diffuse * MeSH
• Child MeSH
• Etoposide MeSH
• Ifosfamide * MeSH
• Carboplatin MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Rituximab MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

The consumption of hazardous antineoplastic drugs (ADs) used in anticancer chemotherapies is steadily increasing representing thus risks to both human health and the environment. Hospitals may serve as a contamination source, and pharmacists preparing the antineoplastic drugs (ADs) as well as nurses administering chemotherapy and caring for oncology patients are among the healthcare professionals being highly exposed. Here, we present the results of systematic monitoring (2018-2020) of surface contamination by 13 ADs in the pharmacies and hospitals in the Czech Republic (CZ; large-scale monitoring, 20 workplaces) and Slovak Republic (SK; pilot study at 4 workplaces). The study evaluated contamination by three commonly monitored ADs, i.e., 5-fluorouracil (FU), cyclophosphamide (CP), and platinum (total Pt representing cis-, carbo-, and oxaliplatin) together with ten less explored ADs, i.e., gemcitabine (GEM), ifosfamide (IF), paclitaxel (PX), irinotecan (IRI), docetaxel (DOC), methotrexate (MET), etoposide (ETOP), capecitabine (CAP), imatinib (IMAT), and doxorubicin (DOX). Floors and desktop surfaces in hospitals (chemotherapy application rooms, nurse working areas) were found to be more contaminated, namely with CP and Pt, in both countries when compared to pharmacies. Comparison between the countries showed that hospital surfaces in SK are generally more contaminated (e.g., CP median was 20 times higher in SK), while some pharmacy areas in the CZ were more contamined in comparison with SK. The newly studied ADs were detected at lower concentrations in comparison to FU, CP, and Pt, but some markers (GEM, IF, PX, and IRI) were frequently observed, and adding these compounds to routine monitoring is recommended.

• MeSH
• Antineoplastic Agents * analysis   MeSH
• Cyclophosphamide analysis   MeSH
• Fluorouracil analysis   MeSH
• Ifosfamide analysis   MeSH
• Equipment Contamination MeSH
• Pharmacies * MeSH
• Humans MeSH
• Environmental Monitoring methods   MeSH
• Hospitals MeSH
• Pilot Projects MeSH
• Occupational Exposure * analysis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Slovakia MeSH

PURPOSE: Most aspects of osteosarcoma have been addressed in detail, but there is no comprehensive analysis of deceased patients and causes of death. METHODS: The database of the Cooperative Osteosarcoma Study Group COSS (1980-03/31/2021; 4475 registered high-grade central osteosarcoma patients) was searched deaths from any cause. Affected patients were analyzed for demographic and baseline variables and disease-status at the time of demise. Deaths from causes other than osteosarcoma were analyzed in detail. RESULTS: A total of 1520 deceased patients were identified (median age (range) at osteosarcoma diagnosis 16 (2-78) years; 908 (59.7%) male, 612 (40.3%) female; primary tumor: extremities 1263 (83.1%), trunk 208 (13.7%), craniofacial 47 (3.1%) (site unknown 2); metastases at registration: absent 1.051 (69.1%), present 466 (30.7%) (3 no data). The median time from diagnosis to death was 2.22 (0.08-32.02) years. 1286 (84.6%) patients succumbed to osteosarcoma (370 without achieving complete remission, 488 first, 428 more than one recurrences), 146 (9.6%) to other, 88 (5.8%) to unknown causes. Chemotherapy-related infections (40), secondary malignancies (39), and perioperative complications (19) were among the most frequent potentially treatment-related causes, and high-dose methotrexate (19), doxorubicin (17), and ifosfamide (15) were the drugs most commonly held responsible. Patients with unknown causes of death had an unusually long median follow-up. CONCLUSION: The major cause of death of patients after osteosarcoma is this malignancy, mostly from one of its multiple relapses. However, almost 10% of fatalities are due to other documented causes. Some of these deaths may be preventable with the knowledge gained from comprehensive analyses such as this.

• MeSH
• Cisplatin therapeutic use   MeSH
• Doxorubicin therapeutic use   MeSH
• Ifosfamide therapeutic use   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Methotrexate MeSH
• Adolescent MeSH
• Bone Neoplasms * drug therapy   MeSH
• Osteosarcoma * drug therapy   MeSH
• Cause of Death MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Fibromatosis, Aggressive drug therapy   surgery   therapy   MeSH
• Anthracyclines therapeutic use   MeSH
• Early Diagnosis MeSH
• Ifosfamide administration & dosage   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Antibodies, Monoclonal therapeutic use   MeSH
• Uterine Neoplasms drug therapy   surgery   classification   therapy   MeSH
• Thoracic Neoplasms surgery   MeSH
• Soft Tissue Neoplasms * diagnostic imaging   diagnosis   etiology   surgery   MeSH
• Breast Neoplasms drug therapy   classification   secondary   MeSH
• Antineoplastic Combined Chemotherapy Protocols * MeSH
• Radiotherapy MeSH
• Retroperitoneal Neoplasms diagnostic imaging   diagnosis   surgery   MeSH
• Sarcoma * diagnosis   etiology   surgery   classification   radiotherapy   MeSH
• Neoplasm Staging methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Introduction: Macrocrystalline oxides of alkaline earth metals (Mg and Ca) or light metals (Al and Ti) can respond to standard warfare agents such as sulfur mustard, soman, or agent VX. In this paper, we compared the decontamination ability of sodium hydroxide (NaOH) and sodium hypochlorite (NaClO) for nitrogen mustards (cyclophosphamide [CP] and ifosfamide [IFOS]) with a new procedure using a destructive sorbent based on nanocrystalline and nanodispersive titanium dioxide (TiO2) as a new efficient and cheap material for complete decontamination of surfaces. Methods: Titanium (IV) dioxide nanoparticles were prepared by the homogeneous hydrolysis of titanium(IV) oxysulfate (TiOSO4) with urea. The as-prepared TiO2 nanoparticles were used for the fast and safe decontamination of cytostatics from the nitrogen mustard family (CP and IFOS) in water. The adsorption-degradation process of cytostatics in the presence of TiO2 was compared with decontamination agents (0.01 M solution of sodium hydroxide and 5% solution of sodium hypochlorite). The mechanism of the decontamination process and the degradation efficiency were determined by high-performance liquid chromatography with mass spectrometry. Results: It was demonstrated that a 0.01 M solution of sodium hydroxide (NaOH) decomposes CP to 3-((amino(bis(2-chloroethyl)amino)phosphoryl)oxy)propanoic acid and sodium hypochlorite formed two reaction products, namely, IFOS and 4-hydroxy-cyclophosphamide. IFOS is cytotoxic, and 4-hydroxy-cyclophosphamide is a known metabolite of CP after its partial metabolism by CYP/CYP450. IFOS degrades in the pres¬ence of NaOH to toxic IFOS mustard. Titanium(IV) dioxide nanoparticles adsorbed on its surface CP after 5 minutes and on IFOS after 10 minutes. The adsorption-degradation process of CP in water and in the presence of TiO2 led to 4-hydroxy-cyclophosphamide and IFOS, respectively, which decayed to oxidation product 4-hydroxy-ifosfamide. Conclusion: Nanodispersive TiO2 is an effective degradation agent for decontamination of surfaces from cytostatics in medical facilities.

• MeSH
• Antineoplastic Agents, Alkylating chemistry   metabolism   MeSH
• Cyclophosphamide chemistry   metabolism   MeSH
• Cytostatic Agents chemistry   metabolism   MeSH
• Decontamination methods   MeSH
• Ifosfamide chemistry   metabolism   MeSH
• Humans MeSH
• Nanoparticles chemistry   MeSH
• Titanium chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Sarkomy měkkých tkání (soft tissue sarcomas, STS) patří mezi nádory raritní. Dne 28. května 2018 byla online publikována v časopise Annals of Oncology aktualizovaná doporučení ESMO‑EURACAN (European Society for Medical Oncology – European Reference Network for rare adult solid cancer) pro diagnostiku, léčbu a sledování pacientů s měkkotkáňovými sarkomy. Chirurgická léčba doplněná v indikovaných případech ozářením je u STS dospělých léčbou standardní ve většině případů. Postavení systémové léčby lokalizovaného onemocnění není jasně definováno. Jinak je tomu v případě relabující nebo metastatické nemoci. Sdělení shrnuje současný pohled na indikace a možnosti farmakoterapie v léčbě měkkotkáňových sarkomů vyjma gastrointestinálních stromálních tumorů (GIST).

Soft Tissue Sarcomas (STS) represent a heterogenous group of rare malignancies. Updated soft tissue and visceral sarcomas ESMO‑EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow‑up (from the European Society for Medical Oncology – European Reference Network for rare adult solid cancer) were published online on the 28th May 2018 in the Annals of Oncology. Surgery (+ radiation therapy in selected cases) is the standard treatment for adult‑type localized soft tissue sarcomas in the majority of cases. Systemic therapy is not a standard treatment of localized STS yet. They have their place in the treatment of advanced, relapsed or metastatic STS. The article provides a brief description of pharmacotherapeutic options for STS, except for gastrointestinal stromal tumors (GIST).

• MeSH
• Antibiotics, Antineoplastic therapeutic use   MeSH
• Antineoplastic Agents, Alkylating therapeutic use   MeSH
• Doxorubicin therapeutic use   MeSH
• Ifosfamide therapeutic use   MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Sarcoma * diagnosis   therapy   MeSH
• Practice Guidelines as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Methylenová modř je syntetická látka používaná v medicíně již více než 120 let. Tento článek shrnuje její základní farmakologické vlastnosti a oblast použití jako léčiva i zdravotnického prostředku. Jsou osvětleny mechanismy působení methylenové modři, a to jak specifické, tedy ovlivnění enzymů a zapojení do přenosu elektronů v dýchacím řetězci, tak i nespecifické, dané fyzikálně chemickým působením i vlastnostmi předurčujícími látku k antioxidačním účinkům. Dále jsou zmíněny farmakokinetické parametry, interakce, nežádoucí účinky a toxicita; schválené indikace a oblast použití zdravotnických prostředků.

Methylene blue is a synthetic substance used in medicine for more than 120 years. This review summarizes its basic pharmacological properties and its use as a drug and a medical device. Mechanisms of action of methylene blue are presented, both specific, i.e. enzyme inhibition and involvement in electron transfer in the respiratory chain, as well as non specific mechanisms which are based on physico chemical characteristics, predetermining its antioxidant properties. In addition, pharmacokinetic parameters, pharmacokinetic interactions, adverse effects and toxicity plus approved indications and use related to medical devices are reviewed.

• MeSH
• Alzheimer Disease drug therapy   MeSH
• Staining and Labeling methods   utilization   MeSH
• Endoscopy, Digestive System methods   utilization   MeSH
• Pharmacologic Actions MeSH
• Drug Evaluation * methods   utilization   MeSH
• Ifosfamide poisoning   toxicity   MeSH
• Skin Diseases, Infectious drug therapy   MeSH
• Humans MeSH
• Malaria drug therapy   MeSH
• Methemoglobinemia drug therapy   MeSH
• Methylene Blue * administration & dosage   adverse effects   therapeutic use   MeSH
• Drug Approval methods   legislation & jurisprudence   MeSH
• Statistics as Topic MeSH
• Therapeutic Uses * MeSH
• Vasoplegia drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH