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
• acidóza chemicky indukované   etiologie   MeSH
• dospělí MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• Ewingův sarkom * diagnostické zobrazování   farmakoterapie   komplikace   patofyziologie   MeSH
• Fanconiho syndrom * chemicky indukované   patologie   MeSH
• ifosfamid aplikace a dávkování   škodlivé účinky   MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-etoposide) showed a significant improvement in overall survival versus platinum-etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide alone. METHODS: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum-etoposide, durvalumab plus platinum-etoposide, or platinum-etoposide alone. In all groups, patients received etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL/min or cisplatin 75-80 mg/m2 on day 1 of each cycle. Patients in the platinum-etoposide group received up to six cycles of platinum-etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum-etoposide versus platinum-etoposide and for durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. FINDINGS: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum-etoposide, 268 to durvalumab plus platinum-etoposide, and 269 to platinum-etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3-27·9). Durvalumab plus tremelimumab plus platinum-etoposide was not associated with a significant improvement in overall survival versus platinum-etoposide (hazard ratio [HR] 0·82 [95% CI 0·68-1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6-12·0) versus 10·5 months (9·3-11·2). Durvalumab plus platinum-etoposide showed sustained improvement in overall survival versus platinum-etoposide (HR 0·75 [95% CI 0·62-0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3-14·7) versus 10·5 months (9·3-11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum-etoposide group, and 88 [33%] of 266 patients in the platinum-etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 85 (32%) in the durvalumab plus platinum-etoposide group, and 97 (36%) in the platinum-etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum-etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum-etoposide group (pancytopenia and thrombocytopenia [n=1 each]). INTERPRETATION: First-line durvalumab plus platinum-etoposide showed sustained overall survival improvement versus platinum-etoposide but the addition of tremelimumab to durvalumab plus platinum-etoposide did not significantly improve outcomes versus platinum-etoposide. These results support the use of durvalumab plus platinum-etoposide as a new standard of care for the first-line treatment of ES-SCLC. FUNDING: AstraZeneca.

• MeSH
• časové faktory MeSH
• cisplatina aplikace a dávkování   škodlivé účinky   MeSH
• doba přežití bez progrese choroby MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• karboplatina aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom plic farmakoterapie   mortalita   patologie   MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• nádory plic farmakoterapie   mortalita   patologie   MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

RATIONALE: The use of cisplatin in patients with chronic kidney disease (CKD) is risky and depends on a number of factors. The optimal procedure in stage I of a non seminomatous germ cell tumor without proven lymphangioinvasion after orchiectomy is controversial and is the subject of a number of discussions due to the lack of randomized studies assessing individual treatment options. The adjuvant method of choice is surveillance or application of cisplatin-based chemotherapy with the risk of treatment related nephrotoxicity. Information about cisplatin safety in renal transplant patients is particularly limited. The aim of this paper is to share the experience with the application of adjuvant chemotherapy Bleomycin, Etoposide, Cisplatin (BEP) in high-risk patient with nonseminoma after kidney transplantation. PATIENT CONCERNS: We report a case report of rare group of high-risk patient with non-seminomatous germ cell testicular tumor (NSGCT) after kidney transplantation before application of adjuvant chemotherapy BEP. Patient presented with month-long discomfort in the scrotal area. Previously, he was treated with chronic kidney disease based on chronic glomerulonephritis, which was treated with repeated kidney transplantation. DIAGNOSIS: The ultrasound examination for a month-long discomfort in the scrotal area found a solid mass of the left testis. Radical inguinal orchiectomy confirmed NSGCT with the presence of lymphovascular invasion (LVI). Postoperative staging with computed tomography of the chest and abdomen did not show obvious dissemination of the disease. INTERVENTIONS: Reducing original dose of chemotherapeutics according to the recommendations of the summary of product characteristics led to only a transient increase in creatinine levels. OUTCOMES: The 5-year risk of relapse in surveillance was reduced to around 3% by applying cisplatin-based chemotherapy. LESSONS: Application of cisplatin-based chemotherapy is safe and effective in patients with CKD and in patients with a kidney transplant.

• MeSH
• adjuvantní chemoterapie MeSH
• bleomycin škodlivé účinky   terapeutické užití   MeSH
• chronická renální insuficience komplikace   imunologie   chirurgie   MeSH
• cisplatina škodlivé účinky   terapeutické užití   MeSH
• etoposid škodlivé účinky   terapeutické užití   MeSH
• germinální a embryonální nádory komplikace   farmakoterapie   chirurgie   MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• orchiektomie MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• testikulární nádory komplikace   farmakoterapie   chirurgie   MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC. METHODS: This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum-etoposide; durvalumab plus tremelimumab plus platinum-etoposide; or platinum-etoposide alone. All drugs were administered intravenously. Platinum-etoposide consisted of etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum-etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum-etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum-etoposide group versus the platinum-etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. FINDINGS: Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum-etoposide group and 269 to the platinum-etoposide group. Durvalumab plus platinum-etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59-0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5-14·8) in the durvalumab plus platinum-etoposide group versus 10·3 months (9·3-11·2) in the platinum-etoposide group, with 34% (26·9-41·0) versus 25% (18·4-31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum-etoposide group and 166 (62%) of 266 in the platinum-etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. INTERPRETATION: First-line durvalumab plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. FUNDING: AstraZeneca.

• MeSH
• cisplatina aplikace a dávkování   škodlivé účinky   MeSH
• doba přežití bez progrese choroby MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• fytogenní protinádorové látky aplikace a dávkování   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   MeSH
• karboplatina aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom plic farmakoterapie   mortalita   MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• nádory plic farmakoterapie   mortalita   MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Purpose The prognostic effect of isolated infradiaphragmatic involvement in Hodgkin lymphoma (HL) is controversial, and there are little data about patients treated with current therapies. Therefore, we performed a risk factor analysis to focus on isolated nodal infradiaphragmatic disease in patients treated within the German Hodgkin Study Group trials HD13 (clinical trial information: ISRCTN63474366) and HD14 (clinical trial information: ISRCTN04761296) for early-stage HL. Patients and Methods Characteristics and outcomes of patients who had infradiaphragmatic HL were compared with patients who had supradiaphragmatic disease. Progression-free survival (PFS) and overall survival (OS) were estimated according to Kaplan-Meier methods and were compared between groups using the log-rank test and Cox proportional hazards regression, which was also applied for multivariable analyses that adjusted for relevant baseline characteristics. Results Of 2,903 qualified patients, 223 (7.7%) were diagnosed with isolated nodal infradiaphragmatic disease. In general, these patients were older, had a poorer performance status, were more often male, and had the nodular sclerosis subtype less often than those with supradiaphragmatic disease. After a median follow-up time of 51 months, PFS and OS were significantly worse in patients with infradiaphragmatic disease (5-year PFS and OS, 80.1% and 91.5% v 91.2% and 97.6% in patients with supradiaphragmatic disease; each P < .001). In multivariable analyses, infradiaphragmatic HL remained a significant risk factor in terms of PFS (hazard ratio [HR], 1.5; 95% CI, 1.04 to 2.2; P = .03) and OS (HR, 2.0; 95% CI, 1.2 to 3.5; P = .01). However, inferior PFS and OS could not be observed among those patients treated with the more intensive chemotherapy (two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] in HD13, and two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPPescalated] plus two cycles of ABVD in HD14; all patients received 30 Gy of involved-field radiotherapy). Conclusion Early-stage HL that presents with infradiaphragmatic disease only represents a distinct patient group with an inferior outcome. However, this adverse outcome can be outweighed by appropriate combined modality treatment.

• MeSH
• bleomycin aplikace a dávkování   škodlivé účinky   MeSH
• chemoradioterapie metody   MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• dakarbazin aplikace a dávkování   škodlivé účinky   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• Hodgkinova nemoc mortalita   patologie   terapie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• prokarbazin aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

The metronomic therapy concept uses low doses of continuously applied chemotherapeutic, anti-angiogenetic, and immunomodulating drugs. Twenty patients with recurrent and 3 with refractory high-risk neuroblastoma were treated by the metronomic concept using celecoxib, cyclophosphamide, vinblastine, and etoposide for up to 24 months. The outcome was compared to 274 matched patients with a first recurrence from stage 4 neuroblastoma using the variables time from diagnosis to first recurrence, number of organs involved, and MYCN amplification. All were treated with dose-intensive conventional chemotherapy. The study patients experienced 1-3 recurrences and had 1-3 sites involved (osteomedullary, primary tumor, central nervous system, lymph nodes, liver, lungs) before the metronomic therapy started. Two patients in complete remission and three with active refractory disease following recurrence treatment were excluded from the outcome analysis. The curves for secondary event-free and overall survival demonstrated no significant differences. The toxicity was minimal except for ≥3 grade thrombocytopenia and leukopenia (all heavily pretreated). The treatment was realized in an outpatient setting. The metronomic approach is similarly effective as standard treatment in recurrent high-risk neuroblastoma, has low toxicity, and is applicable in an outpatient setting. A prospective study including propranolol as a fifth drug is underway.

• MeSH
• celekoxib aplikace a dávkování   škodlivé účinky   MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• dítě MeSH
• dospělí MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• kojenec MeSH
• lidé MeSH
• lokální recidiva nádoru * farmakoterapie   mortalita   MeSH
• metronomické podávání léků * MeSH
• míra přežití MeSH
• neuroblastom * farmakoterapie   mortalita   MeSH
• pilotní projekty MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• vinblastin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH

• MeSH
• adrenalektomie metody   trendy   využití   MeSH
• bevacizumab aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• cetuximab aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• cisplatina aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Cushingův syndrom * diagnóza   etiologie   terapie   MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• etoposid aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• farmakoterapie * metody   trendy   využití   MeSH
• hrudní chirurgie metody   trendy   MeSH
• hydrokortison izolace a purifikace   MeSH
• hypersekrece ACTH v hypofýze komplikace   patofyziologie   prevence a kontrola   MeSH
• lidé MeSH
• metastázy nádorů diagnóza   prevence a kontrola   terapie   MeSH
• mitotan aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• nádory závislé na hormonech enzymologie   terapie   MeSH
• radiochirurgie * metody   trendy   využití   MeSH
• statistika jako téma MeSH
• streptozocin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

Nejčastější malignitou u mužů ve věku 15–40 let jsou testikulární germinální nádory. Díky vysoké citlivosti k onkologické terapii se jedná o nejlépe léčitelné solidní nádory dospělého věku. Neseminomové germinální testikulární nádory představují přibližně 45 % všech testikulárních nádorů. Většina z nich je zachycena ve stadiu I. Dle doporučení odborných společností je standardní postup po primárně provedené orchiektomii nejednotný. Může být využita možnost pečlivého sledování, chemoterapie na bázi cisplatiny nebo retroperitoneální lymfadenektomie. Pravděpodobnost relapsu závisí na rizikových faktorech, z nichž nejdůležitější roli hraje přítomnost lymfangioinvaze. Cílem našeho sdělení je pomocí níže uvedených kazuistik poukázání na nutnou stratifikaci léčby, vedoucí k minimalizaci nežádoucích účinků se zachováním co nejnižšího počtu relapsů.

The most common malignancy in men aged 15–40 years are testicular germ cell tumors. Thanks to the high sensitivity to oncology therapy belongs to the group of highly curable oncologic diseases with favorable prognoses. Non-seminomatous germ cell tumors represent approximately 45 % of all testicular tumors. Most of them are captured in stage I. According to the recommendations of professional societies is the standard procedure after primarily orchiectomy inconsistent. It can be used surveillance, cisplatin-based chemotherapy or retroperitoneal lymphadenectomy. The probability of relapse depends on risk factors. The most important factor is the presence of lymphovascular invasion. The aim of our report is to use the following case reports to point of necessary stratification which can lead to minimize side effects with maintaining the minimum number of relapses.

• Klíčová slova
• neseminomové germinální testikulární nádory,
• MeSH
• adjuvantní chemoterapie škodlivé účinky   MeSH
• bleomycin škodlivé účinky   terapeutické užití   MeSH
• cisplatina škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• etoposid škodlivé účinky   terapeutické užití   MeSH
• germinální a embryonální nádory * farmakoterapie   chirurgie   patologie   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• nemoci periferního nervového systému chemicky indukované   MeSH
• orchiektomie MeSH
• parestezie chemicky indukované   MeSH
• pozorné vyčkávání MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• staging nádorů MeSH
• testikulární nádory * farmakoterapie   chirurgie   patologie   MeSH
• zapojení pacienta MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Purpose Patients with extensive-stage disease small-cell lung cancer (SCLC) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum. This randomized, double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC. Patients and Methods Patients were randomly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum (cisplatin or carboplatin) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule (chemotherapy in cycles one to four; ipilimumab or placebo beginning in cycle three up to cycle six), followed by ipilimumab or placebo maintenance every 12 weeks. Primary end point was overall survival (OS) among patients receiving at least one dose of blinded study therapy. Results Of 1,132 patients randomly assigned, 954 received at least one dose of study therapy (chemotherapy plus ipilimumab, n = 478; chemotherapy plus placebo, n = 476). Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo (hazard ratio, 0.94; 95% CI, 0.81 to 1.09; P = .3775). Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo (hazard ratio, 0.85; 95% CI, 0.75 to 0.97). Rates and severity of treatment-related adverse events were similar between arms, except for diarrhea, rash, and colitis, which were more frequent with chemotherapy plus ipilimumab. Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab (18% v 2% with chemotherapy plus placebo). Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo. Conclusion Addition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC. No new or unexpected adverse events were observed with chemotherapy plus ipilimumab. Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC.

• MeSH
• cisplatina aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• ipilimumab aplikace a dávkování   škodlivé účinky   MeSH
• Kaplanův-Meierův odhad MeSH
• karboplatina aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom plic farmakoterapie   patologie   MeSH
• nádory plic farmakoterapie   patologie   MeSH
• neutropenie chemicky indukované   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• průjem chemicky indukované   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Tregs play a suppressive role in the control of antitumour immunity. In this study we evaluated the relevance of prospective monitoring of peripheral blood regulatory T cells (Tregs) as a potential prognostic marker of future outcome of epithelial ovarian cancer in patients with or without a metronomic chemotherapy. METHODS: 46 patients diagnosed with the ovarian cancer were enrolled in the study and divided into groups according to the stage of the disease, outcome of the surgery and treatment received. Proportions of Tregs in the peripheral blood samples were evaluated using flow cytometry. RESULTS: We show that the early stage of the disease and absence of the tumor residuum after radical surgery are the most important factors predicting a favourable clinical outcome in the ovarian cancer. We did not show any significant effect of consolidation chemotherapy with metronomic doses of etoposide or cyclophosphamide on the peripheral blood Tregs and on the clinical outcome. The slope of the Tregs trend line was a significant predictor of an early relapse, even after controlling for stage and tumor residuum after the surgical debulking by using the Cox proportional hazard model. CONCLUSIONS: This study shows that the faster kinetics of Tregs increase in the peripheral blood, expressed as the slope of the Tregs trend line, is a significant predictor of ovarian cancer early relapse hazard. However, due to its relatively low specificity, the informative value of regular monitoring of Tregs kinetics in the peripheral blood for the subsequent clinical outcome is limited.

• MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• etoposid aplikace a dávkování   škodlivé účinky   MeSH
• imunofenotypizace MeSH
• karcinom diagnóza   farmakoterapie   imunologie   MeSH
• krevní oběh MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• metronomické podávání léků * MeSH
• monitorování imunologické metody   MeSH
• nádory vaječníků diagnóza   farmakoterapie   imunologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• prospektivní studie MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   MeSH
• regulační T-lymfocyty účinky léků   imunologie   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH