BACKGROUND: There are no reports of concurrent chemoradiotherapy for gastric cancer with peritoneal oligometastases. CASE DESCRIPTION: A 70-year-old man with gastric cancer and peritoneal oligometastases received concurrent adaptive radiotherapy and oral S-1. After radiotherapy, S-1 was discontinued, and 2 years later the tumor had completely regressed, with no recurrence or metastasis 6 years after radiotherapy. CONCLUSION: Peritoneal oligometastatic gastric cancer may be a candidate for curative treatment with concurrent adaptive radiotherapy and oral S-1.

• Klíčová slova
• Drug therapy, image-guided radiotherapy, intensity-modulated radiotherapy, stomach neoplasms,
• MeSH
• chemoradioterapie * MeSH
• fixní kombinace léků MeSH
• ftorafur * terapeutické užití   aplikace a dávkování   MeSH
• kyselina oxonová * terapeutické užití   aplikace a dávkování   MeSH
• lidé MeSH
• nádory žaludku * patologie   terapie   farmakoterapie   MeSH
• peritoneální nádory * sekundární   terapie   MeSH
• protinádorové antimetabolity terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• fixní kombinace léků MeSH
• ftorafur * MeSH
• kyselina oxonová * MeSH
• protinádorové antimetabolity MeSH
• S 1 (combination) MeSH Prohlížeč

BACKGROUND: This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). METHODS: Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. RESULTS: DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. CONCLUSIONS: The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.

• Klíčová slova
• Advanced gastric cancer, Epirubicin, First-line chemotherapy, Oxaliplatin, S-1,
• MeSH
• aplikace orální MeSH
• dospělí MeSH
• epirubicin aplikace a dávkování   MeSH
• fixní kombinace léků MeSH
• ftorafur aplikace a dávkování   MeSH
• gastroezofageální junkce účinky léků   patologie   MeSH
• invazivní růst nádoru MeSH
• kyselina oxonová aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• maximální tolerovaná dávka MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• nádory jícnu farmakoterapie   sekundární   MeSH
• nádory žaludku farmakoterapie   sekundární   MeSH
• nádory farmakoterapie   patologie   MeSH
• následné studie MeSH
• organoplatinové sloučeniny aplikace a dávkování   MeSH
• oxaliplatin MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• multicentrická studie MeSH
• Názvy látek
• epirubicin MeSH
• fixní kombinace léků MeSH
• ftorafur MeSH
• kyselina oxonová MeSH
• organoplatinové sloučeniny MeSH
• oxaliplatin MeSH
• S 1 (combination) MeSH Prohlížeč

BACKGROUND: The best-known cause of intolerance to fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD) deficiency, which can result from deleterious polymorphisms in the gene encoding DPD (DPYD), including DPYD*2A and c.2846A>T. Three other variants-DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A-have been associated with DPD deficiency, but no definitive evidence for the clinical validity of these variants is available. The primary objective of this systematic review and meta-analysis was to assess the clinical validity of c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity. METHODS: We did a systematic review of the literature published before Dec 17, 2014, to identify cohort studies investigating associations between DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A and severe (grade ≥3) fluoropyrimidine-associated toxicity in patients treated with fluoropyrimidines (fluorouracil, capecitabine, or tegafur-uracil as single agents, in combination with other anticancer drugs, or with radiotherapy). Individual patient data were retrieved and analysed in a multivariable analysis to obtain an adjusted relative risk (RR). Effect estimates were pooled by use of a random-effects meta-analysis. The threshold for significance was set at a p value of less than 0·0167 (Bonferroni correction). FINDINGS: 7365 patients from eight studies were included in the meta-analysis. DPYD c.1679T>G was significantly associated with fluoropyrimidine-associated toxicity (adjusted RR 4·40, 95% CI 2·08-9·30, p<0·0001), as was c.1236G>A/HapB3 (1·59, 1·29-1·97, p<0·0001). The association between c.1601G>A and fluoropyrimidine-associated toxicity was not significant (adjusted RR 1·52, 95% CI 0·86-2·70, p=0·15). Analysis of individual types of toxicity showed consistent associations of c.1679T>G and c.1236G>A/HapB3 with gastrointestinal toxicity (adjusted RR 5·72, 95% CI 1·40-23·33, p=0·015; and 2·04, 1·49-2·78, p<0·0001, respectively) and haematological toxicity (adjusted RR 9·76, 95% CI 3·03-31·48, p=0·00014; and 2·07, 1·17-3·68, p=0·013, respectively), but not with hand-foot syndrome. DPYD*2A and c.2846A>T were also significantly associated with severe fluoropyrimidine-associated toxicity (adjusted RR 2·85, 95% CI 1·75-4·62, p<0·0001; and 3·02, 2·22-4·10, p<0·0001, respectively). INTERPRETATION: DPYD variants c.1679T>G and c.1236G>A/HapB3 are clinically relevant predictors of fluoropyrimidine-associated toxicity. Upfront screening for these variants, in addition to the established variants DPYD*2A and c.2846A>T, is recommended to improve the safety of patients with cancer treated with fluoropyrimidines. FUNDING: None.

• MeSH
• capecitabinum škodlivé účinky   farmakokinetika   MeSH
• dihydrouracildehydrogenasa (NADP) genetika   metabolismus   MeSH
• farmakogenetika MeSH
• fenotyp MeSH
• fluoruracil škodlivé účinky   farmakokinetika   MeSH
• ftorafur škodlivé účinky   farmakokinetika   MeSH
• gastrointestinální nemoci chemicky indukované   diagnóza   genetika   MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• krevní nemoci chemicky indukované   diagnóza   genetika   MeSH
• lidé MeSH
• multivariační analýza MeSH
• nádory diagnóza   farmakoterapie   genetika   MeSH
• odds ratio MeSH
• polymorfismus genetický * MeSH
• protinádorové antimetabolity škodlivé účinky   farmakokinetika   MeSH
• rizikové faktory MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• capecitabinum MeSH
• dihydrouracildehydrogenasa (NADP) MeSH
• fluoruracil MeSH
• ftorafur MeSH
• protinádorové antimetabolity MeSH

BACKGROUND: Prognosis of patients with metastatic gastric cancer is abysmal, usually just a few months. S-1 is a peroral fluoropyrimidine antitumor drug. It is a fixed combination of three effective drugs - tegafur, gimeracil and oteracil potassium. CASE: This is a case report of a 71-year-old man treated for local advanced and metastatic gastric carcinoma treated with combination of S-1 and cisplatin as a first line of therapy. Treatment response reached partial remission and lasted for six months. Treatment was very well tolerated, with no grade 3 and 4 toxicity. After progression, the patient was treated with further lines of therapy. CONCLUSION: In the Czech Republic, experience with S-1 drug is very limited. Our case report showed a good treatment response and minimal toxicity of this treatment, in concordance with results of the study FLAGS.

• MeSH
• cisplatina aplikace a dávkování   MeSH
• fixní kombinace léků MeSH
• ftorafur aplikace a dávkování   MeSH
• karcinom farmakoterapie   sekundární   MeSH
• kyselina oxonová aplikace a dávkování   MeSH
• lidé MeSH
• nádory žaludku farmakoterapie   patologie   MeSH
• protinádorové antimetabolity terapeutické užití   MeSH
• protinádorové látky terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• pyridiny aplikace a dávkování   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cisplatina MeSH
• fixní kombinace léků MeSH
• ftorafur MeSH
• gimeracil MeSH Prohlížeč
• kyselina oxonová MeSH
• protinádorové antimetabolity MeSH
• protinádorové látky MeSH
• pyridiny MeSH
• S 1 (combination) MeSH Prohlížeč

PURPOSE: Mucositis represents one of the most common side effects of chemotherapy, and may affect any part of the gastrointestinal tract, resulting in stomatitis, dysphagia, dyspepsia, or diarrhea. The aim of the present study was to evaluate intestinal permeability in patients with stomatitis during treatment with oral granulocyte-monocyte colony-stimulating factor (GM-CSF, Leucomax). METHODS: Ten patients with chemotherapy-induced stomatitis and 21 control cancer patients were included in the study. Intestinal permeability in patients with stomatitis was evaluated before and after the treatment with oral GM-CSF (200 micrograms for 4 consecutive days) by measuring urinary lactulose, D-xylose, and mannitol after oral challenge in collected urine using capillary gas chromatography. RESULTS: Mean grade of stomatitis (3, range 2-3) improved during treatment by a mean of 1 grade (range 0-2, sign test P < 0.05) with an improvement observed in eight of ten patients. Lactulose excretion, lactulose/mannitol, and lactulose/xylose ratios were markedly elevated in the patients with mucositis compared with 21 control cancer patients (1.60 +/- 1.04%, 0.2446 +/- 0.2937, and 0.3877 +/- 0.6808 vs 0.35 +/- 0.20%, 0.0332 +/- 0.0148, and 0.0255 +/- 0.0086, respectively, Mann Whitney U-test, P < 0.001). After treatment, lactulose excretion, lactulose/mannitol, and lactulose/xylose ratio decreased significantly (1.60 +/- 1.04 vs 0.63 +/- 0.42%; 0.2446 +/- 0.2937 vs 0.1303 +/- 0.1149; and 0.3877 +/- 0.6808 vs 0.1126 +/- 0.1146, respectively, P < 0.05). CONCLUSIONS: Lactulose excretion after oral challenge, lactulose/mannitol, or lactulose/xylose ratio may be useful markers for intestinal involvement in chemotherapy-induced mucositis. Improvement of oral mucositis was associated with a significant decrease of intestinal permeability to lactulose. Testing of intestinal permeability by the present method may be useful to evaluate the effect of therapeutic interventions in patients with chemotherapy-induced mucositis.

• MeSH
• cisplatina aplikace a dávkování   škodlivé účinky   MeSH
• deoxycytidin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   MeSH
• faktor stimulující granulocyto-makrofágové kolonie terapeutické užití   MeSH
• fluoruracil aplikace a dávkování   škodlivé účinky   MeSH
• ftorafur aplikace a dávkování   škodlivé účinky   MeSH
• gemcitabin MeSH
• hodnocení léčiv MeSH
• intestinální absorpce účinky léků   MeSH
• laktulosa farmakokinetika   moč   MeSH
• leukovorin aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mannitol farmakokinetika   moč   MeSH
• nádory trávicího systému komplikace   farmakoterapie   MeSH
• paclitaxel aplikace a dávkování   škodlivé účinky   MeSH
• permeabilita účinky léků   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• stomatitida chemicky indukované   farmakoterapie   MeSH
• střevní sliznice účinky léků   patofyziologie   MeSH
• výsledek terapie MeSH
• xylosa farmakokinetika   moč   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cisplatina MeSH
• deoxycytidin MeSH
• doxorubicin MeSH
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• fluoruracil MeSH
• ftorafur MeSH
• gemcitabin MeSH
• laktulosa MeSH
• leukovorin MeSH
• mannitol MeSH
• paclitaxel MeSH
• xylosa MeSH

The polarographic reduction and parameter tg alpha of a series of synthetic 5-fluorouracil derivatives (various 5'-modified nucleosides) were studied. The studied compounds were compared with analogous nucleosides of the uridine series. It was confirmed that the value of tg alpha which may suggest a potential carcinogenic activity of the compound studied, is dependent upon the reducibility of the compound and is associated with the cleavability of the nucleoside bond, i.e. with the ability to liberate fluorouracil. It was found that Ftorafur, an antitumor agent widely used in clinical practice, displayed a very high value of tg alpha. In the group of polyaromates such high tg alpha values had been found in compounds which are known to have carcinogenic activity.

• MeSH
• ftorafur chemie   farmakologie   MeSH
• kyselina lipoová MeSH
• leukemie L1210 MeSH
• nádorové buňky kultivované účinky léků   MeSH
• nukleové kyseliny chemická syntéza   MeSH
• polarografie MeSH
• uracilnukleotidy chemie   MeSH
• uridin analogy a deriváty   chemická syntéza   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 5-fluorouridine MeSH Prohlížeč
• ftorafur MeSH
• kyselina lipoová MeSH
• nukleové kyseliny MeSH
• uracilnukleotidy MeSH
• uridin MeSH

The authors treated 16 patients with advanced prostate carcinoma after previous orchiectomy and further progression of the disease: 9 patients with Cyclophosphamide + Ftorafur + placebo and seven patients with Cyclophosphamide + Ftorafur + Orimeten. They achieved in particular improvement of the subjective complaints, while in both groups there was objective progression of the disease. In the group with Orimeten the objective progression of the disease was slower than in the group where cytostatics alone were administered.

• MeSH
• aminoglutethimid aplikace a dávkování   terapeutické užití   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• ftorafur aplikace a dávkování   MeSH
• karcinom farmakoterapie   patologie   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty farmakoterapie   patologie   MeSH
• protinádorové látky terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• klinické zkoušky MeSH
• Názvy látek
• aminoglutethimid MeSH
• cyklofosfamid MeSH
• ftorafur MeSH
• protinádorové látky MeSH

• MeSH
• chromatografie na tenké vrstvě MeSH
• fluoruracil analogy a deriváty   MeSH
• ftorafur analýza   MeSH
• indikátory a reagencie MeSH
• spektrofotometrie infračervená MeSH
• spektrofotometrie ultrafialová MeSH
• teplota MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• fluoruracil MeSH
• ftorafur MeSH
• indikátory a reagencie MeSH