OBJECTIVE: To evaluate the oncological efficacy and safety of sequential intravesical gemcitabine/docetaxel (Gem/Doce) therapy in a European cohort of patients with high-risk and very-high-risk non-muscle-invasive bladder cancer (NMIBC) after previous Bacillus Calmette-Guérin (BCG) treatment. MATERIALS AND METHODS: Data were retrospectively collected from 95 patients with NMIBC, treated with Gem/Doce at 12 European centres between 2021 and 2024. Patients previously treated with BCG who had completed a full induction course and received at least one follow-up evaluation were included. One-year disease-free survival (DFS), high-grade DFS and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Adverse events (AEs) were recorded through medical interviews. RESULTS: Of 75 patients, 63 (84%) were classified as having high-risk and 12 (16%) as having very-high-risk NMIBC. Over a median (interquartile range) follow-up of 9 (5-14) months, 20 patients (27%) relapsed and five (6.7%) underwent radical cystectomy. The 1-year DFS was 73% (95% confidence interval [CI] 62-86%), 1-year high-grade DFS was 79% (95% CI 68-91%) and 1-year PFS was 95% (95% CI 90-100%). AEs occurred in 34 patients (45%), with six (8.7%) experiencing severe AEs. Limitations of the study include the short follow-up and variability in both treatment dwelling times and dosage across centres. CONCLUSION: The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients with high- and very-high-risk NMIBC previously treated with BCG. Prospective studies and randomised trials are awaited to define the ideal candidates for Gem/Doce therapy and to standardise treatment protocols.
- MeSH
- aplikace intravezikální MeSH
- BCG vakcína terapeutické užití MeSH
- deoxycytidin * analogy a deriváty aplikace a dávkování škodlivé účinky MeSH
- docetaxel * aplikace a dávkování škodlivé účinky MeSH
- gemcitabin MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie mortalita MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL). METHODS: This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (≤50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients. FINDINGS: Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15·9 months (IQR 8·1-25·5) in the olaparib plus abiraterone group and 24·5 months (8·1-27·6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43-100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was -0·10 (95% CI -2·50 to 2·71) in the olaparib plus abiraterone group and -1·20 (-4·15 to 1·74) in the placebo plus abiraterone group (difference 1·30, 95% CI -2·70 to 5·30; p=0·52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0·90 [95% CI 0·62-1·32], p=0·30; worst bone pain HR 0·85 [0·59-1·22], p=0·18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group. INTERPRETATION: In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results. FUNDING: AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
- MeSH
- androgeny MeSH
- androsteny MeSH
- antagonisté androgenů terapeutické užití MeSH
- bolest chemicky indukované MeSH
- docetaxel škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- ftalaziny MeSH
- hodnocení výsledků péče pacientem MeSH
- kvalita života MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * patologie MeSH
- piperaziny MeSH
- prednisolon MeSH
- prednison MeSH
- prostatický specifický antigen * terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky MeSH
- testosteron MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
IMPORTANCE: DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer. OBJECTIVE: To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). DESIGN, SETTING, AND PARTICIPANTS: The VIABLE double-blind, parallel-group, placebo-controlled, phase 3 randomized clinical trial enrolled patients with mCRPC among 177 hospital clinics in the US and Europe between June 2014 and November 2017. Data analyses were performed from December 2019 to July 2020. INTERVENTIONS: Eligible patients were randomized (2:1) to receive DCVAC/PCa (add-on and maintenance) or placebo, both in combination with chemotherapy (docetaxel plus prednisone). The stratification was applied according to geographical region (US or non-US), prior therapy (abiraterone, enzalutamide, or neither), and Eastern Cooperative Oncology Group performance status (0-1 or 2). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks (up to 15 doses). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS), defined as the time from randomization until death due to any cause, in all randomized patients. Survival was compared using 2-sided log-rank test stratified by geographical region, prior therapy with abiraterone and/or enzalutamide, and Eastern Cooperative Oncology Group performance status. RESULTS: A total of 1182 men with mCRPC (median [range] age, 68 [46-89] years) were randomized to receive DCVAC/PCa (n = 787) or placebo (n = 395). Of these, 610 (81.8%) started DCVAC/PCa, and 376 (98.4%) started placebo. There was no difference in OS between the DCVAC/PCa and placebo groups in all randomized patients (median OS, 23.9 months [95% CI, 21.6-25.3] vs 24.3 months [95% CI, 22.6-26.0]; hazard ratio, 1.04; 95% CI, 0.90-1.21; P = .60). No differences in the secondary efficacy end points (radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events) were observed. Treatment-emergent adverse events related to DCVAC/PCa or placebo occurred in 69 of 749 (9.2%) and 48 of 379 (12.7%) patients, respectively. The most common treatment-emergent adverse events (DCVAC/PCa [n = 749] vs placebo [n = 379]) were fatigue (271 [36.2%] vs 152 [40.1%]), alopecia (222 [29.6%] vs 130 [34.3%]), and diarrhea (206 [27.5%] vs 117 [30.9%]). CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS in patients with mCRPC and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02111577.
- MeSH
- dendritické buňky patologie MeSH
- docetaxel škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- imunoterapie škodlivé účinky MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie MeSH
- prednison MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: In the CARD study (NCT02485691), cabazitaxel significantly improved median radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel and progressed ≤12 mo on the alternative agent (abiraterone/enzalutamide). OBJECTIVE: To assess cabazitaxel versus abiraterone/enzalutamide in older (≥70 yr) and younger (<70 yr) patients in CARD. DESIGN, SETTING, AND PARTICIPANTS: Patients with mCRPC were randomized 1:1 to cabazitaxel (25 mg/m2 plus prednisone and granulocyte colony-stimulating factor) versus abiraterone (1000 mg plus prednisone) or enzalutamide (160 mg). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Analyses of rPFS (primary endpoint) and safety by age were prespecified; others were post hoc. Treatment groups were compared using stratified log-rank or Cochran-Mantel-Haenszel tests. RESULTS AND LIMITATIONS: Of the 255 patients randomized, 135 were aged ≥70 yr (median 76 yr). Cabazitaxel, compared with abiraterone/enzalutamide, significantly improved median rPFS in older (8.2 vs 4.5 mo; hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.38-0.89; p = 0.012) and younger (7.4 vs 3.2 mo; HR = 0.47; 95% CI = 0.30-0.74; p < 0.001) patients. The median OS of cabazitaxel versus abiraterone/enzalutamide was 13.9 versus 9.4 mo in older patients (HR = 0.66; 95% CI = 0.41-1.06; p = 0.084), and it was 13.6 versus 11.8 mo in younger patients (HR = 0.66; 95% CI = 0.41-1.08; p = 0.093). Progression-free survival, prostate-specific antigen, and tumor and pain responses favored cabazitaxel, regardless of age. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 58% versus 49% of older patients receiving cabazitaxel versus abiraterone/enzalutamide and 48% versus 42% of younger patients. In older patients, cardiac adverse events were more frequent with abiraterone/enzalutamide; asthenia and diarrhea were more frequent with cabazitaxel. CONCLUSIONS: Cabazitaxel improved efficacy outcomes versus abiraterone/enzalutamide in patients with mCRPC after prior docetaxel and abiraterone/enzalutamide, regardless of age. TEAEs were more frequent among older patients. The cabazitaxel safety profile was manageable across age groups. PATIENT SUMMARY: Clinical trial data showed that cabazitaxel improved survival versus abiraterone/enzalutamide with manageable side effects in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel and the alternative agent (abiraterone/enzalutamide), irrespective of age.
- MeSH
- abirateron terapeutické užití MeSH
- androsteny MeSH
- benzamidy škodlivé účinky terapeutické užití MeSH
- docetaxel škodlivé účinky MeSH
- fenylthiohydantoin škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie MeSH
- nitrily škodlivé účinky terapeutické užití MeSH
- prednison škodlivé účinky MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky MeSH
- senioři MeSH
- taxoidy škodlivé účinky terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- MeSH
- abirateron terapeutické užití MeSH
- docetaxel škodlivé účinky MeSH
- fatální výsledek MeSH
- febrilní neutropenie vyvolaná chemoterapií * prevence a kontrola MeSH
- filgrastim * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci diagnóza farmakoterapie komplikace MeSH
- polyethylenglykoly terapeutické užití MeSH
- senioři MeSH
- taxoidy terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
PURPOSE: To assess the prevalence of sarcopenia and whether body composition parameters are associated with disease progression and overall survival (OS) in castration-resistant prostate cancer (CRPC) patients. MATERIALS AND METHODS: This single-centre retrospective study evaluated data of 186 consecutive patients who underwent chemohormonal therapy between 2005 and 2016 as first-line systemic treatment for CRPC. Skeletal muscle and fat indices were determined using computerized tomography data before initiation of chemotherapy. Sarcopenia was defined as SMI of <55 cm2/m2. Visceral-to-subcutaneous fat ratio and skeletal muscle volume were calculated with body composition specific areas. Harrell's concordance index was used for predictive accuracy. RESULTS: A total of 154 (82.8%) patients met the criteria for sarcopenia; 139 (74.7%) individuals completed at least six cycles of docetaxel. Within a median follow-up of 24.1 months, age (HR 1.03, 95% CI 1.01-1.06, p = 0.02), high PSA (1.55, 95% CI 1.07-2.25, p = 0.02) and low skeletal muscle volume (HR 1.61, 95% CI 1.10-2.35, p = 0.02) were the only independent prognostic factor for tumor progression. Overall, 93 (50%) patients died during the follow-up period. The established prognosticator, the prechemotherapy presence of liver metastases (HR 1.32, 95% CI 1.08-1.61, p < 0.01) was associated with shorter OS. Moreover, we noted that patients with an elevated visceral-to-subcutaneous fat ratio tended to have a shorter OS (p = 0.06). CONCLUSION: The large majority of men with CRPC suffers from sarcopenia. In our cohort, low skeletal muscle volume was an independent adverse prognosticator for progression of disease. We could not detect a statistically significant body composition parameter for OS, although patients with a high proportion of visceral fat had a trend for shorter OS. However, we suggest that body composition parameters determined by CT data can provide useful objective prognostic factors that may support tailored treatment decision-making.
- MeSH
- docetaxel škodlivé účinky MeSH
- kosterní svaly účinky léků patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádory prostaty rezistentní na kastraci farmakoterapie patologie MeSH
- následné studie MeSH
- prognóza MeSH
- protinádorové látky škodlivé účinky MeSH
- retrospektivní studie MeSH
- sarkopenie chemicky indukované patologie MeSH
- senioři MeSH
- složení těla * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
OBJECTIVES: To obtain routine clinical practice data on cabazitaxel usage patterns for patients with metastatic castration-resistant prostate cancer (mCRPC) and to describe physician-assessed cabazitaxel effectiveness, health-related quality of life (HRQoL) and safety. PATIENTS AND METHODS: CAPRISTANA was an international, observational cohort study examining cabazitaxel use for the treatment of patients with mCRPC. Effectiveness was assessed by overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF) and disease control rate. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P) and the three-level European Quality of Life questionnaire (EQ-5D-3L). Safety was assessed by adverse event (AE) reporting. RESULTS: A total of 189 patients were treated across 54 centres between April 2012 and June 2016. At baseline, 58.7% had ≥1 comorbidity, 93.7% had an Eastern Cooperative Oncology Group performance status ≤1, and 60.1% had a Gleason score at diagnosis of ≥8. Patients received a median of 6 cabazitaxel cycles; 84.7% received cabazitaxel as second-line therapy. The median OS, PFS and TTF were 13.2, 5.6 and 4.4 months, respectively. Cabazitaxel led to disease control in 52.9% of patients. HRQoL was maintained (40.3%) or improved (32.2%) in 72.5% of patients based on total FACT-P scores. Interestingly, 53.6% of patients reported pain improvement and a further 21.2% maintained pain control based on FACT-P prostate cancer-specific pain scores. The most common treatment-related grade ≥3 AEs were neutropenia (7.9%) and anaemia (2.1%). CONCLUSION: Patients in CAPRISTANA treated with cabazitaxel had similar disease outcomes and safety profiles compared with large phase III clinical trials. Most patients had maintained or improved HRQoL scores; >70% of patients had maintained or improved pain control.
- MeSH
- doba přežití bez progrese choroby MeSH
- docetaxel škodlivé účinky terapeutické užití MeSH
- dospělí MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádory prostaty rezistentní na kastraci farmakoterapie mortalita patologie MeSH
- následné studie MeSH
- neutrofily účinky léků MeSH
- protokoly protinádorové kombinované chemoterapie * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- taxoidy terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Metastazující karcinom prostaty má výrazně horší prognózu ve srovnání s lokalizovaným nebo lokálně pokročilým onemocněním. První volbou je u většiny pacientů hormonální, tj. kastrační, léčba. Účinek chemoterapie docetaxelem a nových hormonálních přípravků (abirateron, enzalutamid) byl nejprve prokázán ve stadiu kastrační rezistence. Docetaxel byl dále testován také v kombinaci s hormonální léčbou u nově zjištěných metastáz karcinomu prostaty bez předchozí kastrační léčby. Ve skupině pacientů s kombinovanou léčbou bylo dosaženo výrazně delšího celkového přežití. Významný účinek byl však zaznamenán pouze u pacientů s velkoobjemovým metastatickým onemocněním. Abirateron byl také zkoumán v kombinaci s hormonální léčbou v první linii vysoce rizikového metastazujícího hormonálně senzitivního karcinomu prostaty. Celkové přežití bylo opět výrazně delší pro kombinovanou léčbu. Bezpečnostní profil docetaxelu i abirateronu je příznivý, při volbě mezi těmito přípravky je nutné přihlédnout k celkovém stavu pacienta, jeho symptomům a komorbiditám a také k jeho preferencím.
Metastatic prostate cancer has a significantly worse prognosis compared to localized or locally advanced disease. The first choice in most patients is androgen deprivation therapy, i.e. castration. The effect of docetaxel chemotherapy and novel hormonal agents (abiraterone, enzalutamide) was first demonstrated in the stage of castration resistance. Docetaxel has also been tested in combination with androgen deprivation therapy for newly diagnosed metastatic prostate cancer without prior castration. Significantly longer overall survival was achieved in the group of combined therapy. However, a significant effect was observed only in patients with high volume metastatic disease. Abiraterone has also been studied in combination with androgen deprivation therapy in the first line of therapy of high-risk metastatic hormone-sensitive prostate cancer. Again, overall survival was significantly longer for combined therapy. The safety profile of both docetaxel and abiraterone is favorable, but when choosing between these strategies, one must consider the general condition of the patient, his symptoms and comorbidities as well as his preferences.
- MeSH
- abirateron aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- docetaxel aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- hormonální protinádorové látky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- metastázy nádorů farmakoterapie MeSH
- nádory prostaty * epidemiologie farmakoterapie MeSH
- protinádorové látky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- analýza přežití MeSH
- cisplatina aplikace a dávkování farmakologie škodlivé účinky MeSH
- deoxycytidin analogy a deriváty aplikace a dávkování farmakokinetika škodlivé účinky MeSH
- docetaxel analogy a deriváty aplikace a dávkování farmakologie škodlivé účinky MeSH
- imunoterapie metody MeSH
- karboplatina aplikace a dávkování farmakologie škodlivé účinky MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- nemalobuněčný karcinom plic * farmakoterapie MeSH
- paclitaxel analogy a deriváty aplikace a dávkování farmakologie škodlivé účinky MeSH
- pemetrexed aplikace a dávkování farmakologie škodlivé účinky MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- stupeň nádoru MeSH
- vinorelbin aplikace a dávkování farmakologie škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
