BACKGROUND: Pemetrexed and erlotinib represent novel agents for the treatment of non-small cell lung cancer (NSCLC). The role of sequential treatment in NSCLC has not been elucidated yet. We compared the efficacy of second-line pemetrexed followed by third-line erlotinib (P-E) to treatment with the reverse sequence (E-P). PATIENTS AND METHODS: We analyzed data of 57 patients with advanced-stage (IIIB/IV) lung adenocarcinoma harboring wild-type epidermal growth factor receptor (EGFR) gene; 31 patients were treated with P-E and 26 patients with the E-P sequence. RESULTS: The median progression-free survival (PFS) for patients treated with P-E was 3.6 months vs. 7.8 months for patients treated with E-P (p=0.029). The median overall survival (OS) for patients treated with P-E was 7.9 months vs. 26.3 months for patients treated with E-P (p=0.006). CONCLUSION: The results proved a significant improvement of both PFS and OS for patients treated with the E-P sequence as compared to the P-E sequence.

• Klíčová slova
• NSCLC, Pemetrexed, adenocarcinoma, erlotinib, second-line, sequence, third-line,
• MeSH
• adenokarcinom plic MeSH
• adenokarcinom farmakoterapie   genetika   patologie   MeSH
• chinazoliny terapeutické užití   MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• erlotinib MeSH
• glutamáty terapeutické užití   MeSH
• guanin analogy a deriváty   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic farmakoterapie   genetika   patologie   MeSH
• pemetrexed MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• chinazoliny MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• erlotinib MeSH
• glutamáty MeSH
• guanin MeSH
• pemetrexed MeSH
• protinádorové látky MeSH

Aim: We aimed to compare the mortality rates related to adverse events (AEs) and discontinuation of treatment due to toxicity as well as all AEs of currently used regimens of second-line treatment strategies for advanced or metastatic urothelial carcinoma of the bladder. Methods: The MEDLINE and EMBASE databases were searched for articles according to the PRISMA extension statement for network meta-analysis. Results: Five trials comprising 2205 patients met our eligibility criteria. It is highly likely that immunotherapy, as single regimen, has the lowest rates of motor and sensory neuropathies, constipation, abdominal pain, alopecia, decreased appetite, vomiting and febrile neutropenia. Immunotherapy, in combination regimen, has the lowest rates of anemia and fatigue. Conclusion: Immunotherapy, especially as single regimen, demonstrated the highest favorable tolerability to most AEs.

Lay abstract In the era of precision medicine, the challenge is to identify the patients who are most likely to benefit from different treatment strategies. We believe that findings of the present network meta-analysis may facilitate individualized treatment strategies based on adverse events to guide regarding the potentially best tolerated approach for patients with urothelial carcinoma of the bladder. Immunotherapy, especially as single regimen, demonstrated the highest favorable tolerability to most adverse events.

• Klíčová slova
• RCT, UC, UCB, adverse events, chemotherapy, immunotherapy, network meta-analyses, second-line,
• MeSH
• imunoterapie škodlivé účinky   metody   MeSH
• karcinom z přechodných buněk farmakoterapie   MeSH
• lidé MeSH
• nádory močového měchýře farmakoterapie   MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• síťová metaanalýza MeSH
• záchranná terapie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH
• Názvy látek
• protinádorové látky imunologicky aktivní MeSH

BACKGROUND: Pemetrexed and erlotinib represent different agents commonly used for the second-line treatment of patients with advanced-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We analyzed data of 137 patients with advanced-stage non-squamous NSCLC treated with pemetrexed or erlotinib in the second line. All patients harbored a wild-type epidermal growth factor receptor gene. Genetic testing was performed using a combination of denaturing capillary electrophoresis and direct Sanger sequencing. RESULTS: overall response rate and disease control rate in patients treated with pemetrexed was 20.8% and 62.5% vs. 6.3% and 53.2% in patients treated with erlotinib (p=0.022; p=0.358). Median progression-free and overall survival in patients treated with pemetrexed was 1.6 and 11.3 months vs. 1.9 and 11.4 months in patients treated with erlotinib (p=0.470 and p=0.942, respectively). Erlotinib was associated with skin rash and diarrhea; pemetrexed was associated with hematological toxicity and fatigue. CONCLUSION: A similar efficacy and different, although well-tolerated, toxicity profile of both pemetrexed and erlotinib was shown.

• Klíčová slova
• NSCLC, Pemetrexed, chemotherapy, erlotinib, second-line treatment, targeted treatment,
• MeSH
• erbB receptory genetika   MeSH
• erlotinib terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic farmakoterapie   patologie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   patologie   MeSH
• pemetrexed terapeutické užití   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• erbB receptory MeSH
• erlotinib MeSH
• pemetrexed MeSH

PURPOSE: To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study. METHODS: Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C min,ss) and survival. Kaplan-Meier analysis was used to evaluate survival from patients in the ramucirumab plus folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) treatment arm stratified by C min,ss quartiles (Q). An ordered categorical model analyzed the relationship between C min,ss and safety outcomes. RESULTS: Pharmacokinetic samples from 906 patients were included in exposure-efficacy analyses; samples from 905 patients were included in exposure-safety analyses. A significant association was identified between C min,ss and overall survival (OS) and progression-free survival (PFS) (p < 0.0001 for both). This association remained significant after adjusting for baseline factors associated with OS or PFS (p < 0.0001 for both). Median OS was 11.5, 12.9, 16.4, and 16.7, and 12.4 months for ramucirumab C min,ss Q1, Q2, Q3, Q4, and placebo group, respectively. Median PFS was 5.4, 4.6, 6.8, 8.5, and 5.2 months for ramucirumab C min,ss Q1, Q2, Q3, Q4, and placebo group, respectively. The risk of Grade ≥3 neutropenia was associated with an increase in ramucirumab exposure. CONCLUSIONS: Exploratory exposure-response analyses suggested a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in patients from the RAISE study with mCRC over the ranges of exposures achieved by a dose of 8 mg/kg every 2 weeks in combination with FOLFIRI.

• Klíčová slova
• Colorectal cancer, Exposure–response, FOLFIRI, Ramucirumab, Second line,
• MeSH
• humanizované monoklonální protilátky MeSH
• kolorektální nádory farmakoterapie   patologie   MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• ramucirumab MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• humanizované monoklonální protilátky MeSH
• monoklonální protilátky MeSH
• protinádorové látky MeSH

The primary endpoint of this study was to evaluate the efficacy (objective response rate; ORR) of combined chemotherapy with raltitrexed plus oxaliplatin as second-line treatment in patients with metastatic colorectal cancer (CRC). Secondary endpoints were overall survival (OS), time to progression (TTP) and toxicity (NCI-CTC criteria). The target population were patients with metastatic colorectal adenocarcinoma who progressed after first-line chemotherapy. Treatment consisted of raltitrexed 3 mg/m2 as a 15-minute intravenous (IV) infusion followed 45 minutes later by oxaliplatin 130 mg/m(2) IV as a 2-h infusion on Day 1, repeated every 3 weeks until further disease progression (PD), unacceptable toxicity or the decision of the patient. A total of 51 patients, all with WHO performance status 0-2 received a median of 6 treatment cycles (range 1-11). After 3 cycles, 8 of the 47 evaluable patients (17%) had experienced an ORR, 28 patients (59.6%) had experienced stable disease (SD) and 11 patients (23.4%) had PD. After 6 cycles, 1 of the 29 evaluable patients (3.5%) had an ORR, 13 patients (44.8%) had SD and 15 patients (51.7%) had PD. After a median follow-up of 48.9 weeks, median TTP was 18 weeks and median overall survival was 54.4 weeks. Treatment was well tolerated; grade 3 toxicities occurred in only 5/51 patients (9.8%). The most common toxicities were paraesthesia (62.7%), diarrhoea (23.5%), nausea (41.2%), vomiting (33.3%), hepatotoxicity (25.5%), and hematological toxicity (41.2%). In conclusion, the combination of oxaliplatin plus raltitrexed appears to be effective and well tolerated as second-line therapy in patients with disseminated CRC.

• MeSH
• adenokarcinom farmakoterapie   mortalita   sekundární   MeSH
• chinazoliny aplikace a dávkování   MeSH
• dospělí MeSH
• kolorektální nádory farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů farmakoterapie   MeSH
• organoplatinové sloučeniny aplikace a dávkování   MeSH
• oxaliplatin MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• thiofeny aplikace a dávkování   MeSH
• výsledek terapie MeSH
• záchranná terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• chinazoliny MeSH
• organoplatinové sloučeniny MeSH
• oxaliplatin MeSH
• raltitrexed MeSH Prohlížeč
• thiofeny MeSH

BACKGROUND: Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy. METHODS: We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator's choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival. RESULTS: A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P = 0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects. CONCLUSIONS: In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.).

• MeSH
• analýza přežití MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * farmakoterapie   MeSH
• nádory děložního čípku * farmakoterapie   mortalita   patologie   MeSH
• oligopeptidy * terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• humanizované monoklonální protilátky * MeSH
• oligopeptidy * MeSH
• tisotumab vedotin MeSH Prohlížeč

• Publikační typ
• komentáře MeSH
• úvodníky MeSH

At present, no consensus exists regarding the use of second-line chemotherapy in patients with hormone-refractory prostate cancer (HRPC). A total of 23 patients with evidence of disease progression during or after first-line chemotherapy (epirubicin, etoposide, and dexamethasone) were included in this study. Two second-line treatments were administered throughout the study period (2000-2004) with 15/23 patients receiving carboplatin AUC 3 on day 1 and vinblastine 5 mg/m2 on day 1 of a 21-day cycle and 8/23 patients treated with docetaxel 50 mg/m2 on day 1 of a 21-day cycle. The latter regimen has been used since 2003. The prostate-specific antigen (PSA) level decreased by > or =50% in 3 of 23 patients, corresponding to an overall PSA response rate of 13% (95% confidence interval, 3-34%). The median time to biochemical progression was 9, 24 and 33 weeks, respectively. The median overall survival was 39 weeks (range, 15-73 weeks) with no difference between the two chemotherapy groups (p=0.08). A significant reduction of analgesic use was observed in 2 of 10 patients (20%) who required analgesics for cancer pain upon study entry. The major toxicity was grade 3 thrombocytopenia in 2 of 23 patients (9%). Both second-line treatments, a combination of carboplatin and vinblastine and a monotherapy with docetaxel, showed modest activity at subtoxic doses in patients with HRPC.

• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• časové faktory MeSH
• chemorezistence * MeSH
• dexamethason terapeutické užití   MeSH
• epirubicin terapeutické užití   MeSH
• etoposid terapeutické užití   MeSH
• hormonální protinádorové látky terapeutické užití   MeSH
• hormony metabolismus   MeSH
• karboplatina terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty farmakoterapie   MeSH
• plocha pod křivkou MeSH
• progrese nemoci MeSH
• prostatický specifický antigen biosyntéza   MeSH
• protinádorové látky farmakologie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• trombocytopenie chemicky indukované   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté androgenů MeSH
• dexamethason MeSH
• epirubicin MeSH
• etoposid MeSH
• hormonální protinádorové látky MeSH
• hormony MeSH
• karboplatina MeSH
• prostatický specifický antigen MeSH
• protinádorové látky MeSH

BACKGROUND: Based on the results of phase III trial, vinflunine was approved by European Medicines Agency in 2010 as second line treatment of advanced urothelial cancer in patients with good performance status (ECOG 0- 1). The objective of this prospective observational study was to assess vinflunine treatment of advanced urothelial cancer patients in terms of progression free survival and overall survival, and to evaluate vinflunine toxicity. PATIENTS AND METHODS: From April 2011 to June 2014 a total of 16 patients (100%) with advanced urothelial cancer were treated with vinflunine. The median age was 62 years (range 43- 80) and the median Karnofsky index was 90% (range 80- 100%). Thirteen patients (81.25%) had urothelial bladder cancers, two patients (12.50%) suffered from urothelial cancers of ureter, and one patient (6.25%) had urothelial cancer of unknown origin (histology was obtained from liver metastasis). Histologically, all the lesions were grade 3 tumors (100%). The number of metastatic sites ranged from 1- 4 (median 3). RESULTS: The effect of treatment was evaluated in accord with RECIST: two patients (12.50%) obtained partial remission, three (18.75%) stabilization, eight patients (50.00%) progressed, and treatment was suspended in one case at patients request. Vinflunine toxicity grade 3- 4 included neutropenia in six patients (37.50%), leukopenia in four patients (25.00%), anemia in one patient (6.25%), constipation in three patients (18.75%), and febrile neutropenia in one patient (6.25%). Median overall survival was 5.2 months (95% CI 3.4- 8.8) and median progression-free survival was 2.3 months (95% CI 2.1- 3.2). CONCLUSION: This study summarizes the first Slovak experience with vinflunine therapy. Our data confirmed the efficacy of vinflunine and its acceptable toxicity in the treatment of patients with advanced urothelial cancer previously treated with a platinum-based regimen.Key words: advanced urothelial cancer - vinflunine - progression-free survival - overall survival - side effects.

• MeSH
• analýza přežití MeSH
• cisplatina aplikace a dávkování   MeSH
• deoxycytidin aplikace a dávkování   analogy a deriváty   MeSH
• dospělí MeSH
• fytogenní protinádorové látky škodlivé účinky   terapeutické užití   MeSH
• gemcitabin MeSH
• karcinom z přechodných buněk farmakoterapie   sekundární   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jater farmakoterapie   sekundární   MeSH
• nádory močového měchýře farmakoterapie   MeSH
• nádory močovodu farmakoterapie   MeSH
• nádory neznámé primární lokalizace farmakoterapie   MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• urologické nádory farmakoterapie   patologie   MeSH
• vinblastin škodlivé účinky   analogy a deriváty   terapeutické užití   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
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• cisplatina MeSH
• deoxycytidin MeSH
• fytogenní protinádorové látky MeSH
• gemcitabin MeSH
• vinblastin MeSH
• vinflunine MeSH Prohlížeč

This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide.

• Publikační typ
• časopisecké články MeSH