OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.
- MeSH
- Chemotherapy, Adjuvant MeSH
- Administration, Intravesical MeSH
- BCG Vaccine therapeutic use administration & dosage MeSH
- Cystectomy methods MeSH
- Epirubicin administration & dosage MeSH
- Neoplasm Invasiveness MeSH
- Middle Aged MeSH
- Humans MeSH
- Mitomycin administration & dosage therapeutic use MeSH
- Non-Muscle Invasive Bladder Neoplasms MeSH
- Urinary Bladder Neoplasms * pathology therapy drug therapy mortality MeSH
- Disease-Free Survival MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
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/m(2) followed by oxaliplatin 130 mg/m(2) (maximum 8 cycles) and then S-1 [20 mg/m(2) (cohort 1) or 25 mg/m(2) (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/m(2) 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/m(2) 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/m(2) 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.
- MeSH
- Administration, Oral MeSH
- Adult MeSH
- Epirubicin administration & dosage MeSH
- Drug Combinations MeSH
- Tegafur administration & dosage MeSH
- Esophagogastric Junction drug effects pathology MeSH
- Neoplasm Invasiveness MeSH
- Oxonic Acid administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Maximum Tolerated Dose MeSH
- Survival Rate MeSH
- Young Adult MeSH
- Esophageal Neoplasms drug therapy secondary MeSH
- Stomach Neoplasms drug therapy secondary MeSH
- Neoplasms drug therapy pathology MeSH
- Follow-Up Studies MeSH
- Organoplatinum Compounds administration & dosage MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase I MeSH
- Multicenter Study MeSH
CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial. OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation. EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out. EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5. CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended. PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.
- MeSH
- Administration, Intravesical MeSH
- Time Factors MeSH
- Doxorubicin administration & dosage analogs & derivatives MeSH
- Epirubicin administration & dosage MeSH
- Carcinoma, Transitional Cell mortality pathology therapy MeSH
- Humans MeSH
- Neoplasm Recurrence, Local prevention & control MeSH
- Survival Rate MeSH
- Mitomycin administration & dosage MeSH
- Urinary Bladder Neoplasms mortality pathology therapy MeSH
- Disease Progression MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage MeSH
- Randomized Controlled Trials as Topic MeSH
- Risk Factors MeSH
- Neoplasm Staging MeSH
- Thiotepa administration & dosage MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Review MeSH
- Keywords
- patologická kompletní remise,
- MeSH
- Survival Analysis MeSH
- Anthracyclines administration & dosage pharmacology therapeutic use MeSH
- Surgical Procedures, Operative MeSH
- Molecular Targeted Therapy * methods trends utilization MeSH
- Epirubicin administration & dosage therapeutic use MeSH
- Antineoplastic Agents, Hormonal * administration & dosage pharmacology therapeutic use MeSH
- Remission Induction MeSH
- Induction Chemotherapy methods standards utilization MeSH
- Carboplatin administration & dosage pharmacology therapeutic use MeSH
- Carcinoma * MeSH
- Clinical Trials as Topic MeSH
- Clinical Trials, Phase II as Topic MeSH
- Humans MeSH
- Meta-Analysis as Topic MeSH
- Breast Neoplasms * diagnosis etiology drug therapy therapy MeSH
- Neoadjuvant Therapy * methods utilization MeSH
- Paclitaxel administration & dosage therapeutic use MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Randomized Controlled Trials as Topic methods statistics & numerical data utilization MeSH
- Receptor, ErbB-2 antagonists & inhibitors administration & dosage pharmacology therapeutic use MeSH
- Mastectomy, Segmental utilization MeSH
- Practice Guidelines as Topic MeSH
- Taxoids administration & dosage pharmacology therapeutic use MeSH
- Drug Tolerance MeSH
- Trastuzumab administration & dosage pharmacology therapeutic use MeSH
- Ultrasonics methods trends MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- MeSH
- Adenocarcinoma * MeSH
- Surgical Procedures, Operative MeSH
- Cyclophosphamide administration & dosage adverse effects therapeutic use MeSH
- Carcinoma, Ductal, Breast * MeSH
- Epirubicin administration & dosage adverse effects therapeutic use MeSH
- Glutathione * administration & dosage therapeutic use MeSH
- Complementary Therapies * MeSH
- Ascorbic Acid * administration & dosage therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Mammography utilization MeSH
- Neoadjuvant Therapy MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Orthomolecular Therapy MeSH
- Paclitaxel administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Bevacizumab MeSH
- Cyclophosphamide * administration & dosage adverse effects MeSH
- Adult MeSH
- Epirubicin * administration & dosage adverse effects MeSH
- Fluorouracil * administration & dosage adverse effects MeSH
- Antibodies, Monoclonal, Humanized * administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymph Nodes * pathology drug effects MeSH
- Breast Neoplasms * epidemiology drug therapy pathology MeSH
- Neoadjuvant Therapy MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Receptor, ErbB-2 * genetics MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Taxoids * administration & dosage adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- MeSH
- Chemotherapy, Adjuvant MeSH
- Time Factors MeSH
- Cyclophosphamide administration & dosage adverse effects MeSH
- Adult MeSH
- Epirubicin administration & dosage adverse effects MeSH
- Fluorouracil administration & dosage adverse effects MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Lymph Nodes surgery pathology MeSH
- Mastectomy methods MeSH
- Biomarkers, Tumor analysis MeSH
- Breast Neoplasms drug therapy chemistry surgery pathology MeSH
- Neoadjuvant Therapy methods MeSH
- Paclitaxel administration & dosage adverse effects MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects MeSH
- Receptor, ErbB-2 analysis MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Neoplasm Grading MeSH
- Stroke Volume drug effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Research Support, N.I.H., Extramural MeSH
- Geographicals
- Puerto Rico MeSH
- United States MeSH
- MeSH
- Adenocarcinoma drug therapy chemistry pathology MeSH
- Cyclophosphamide administration & dosage MeSH
- Adult MeSH
- Doxorubicin administration & dosage MeSH
- Epirubicin administration & dosage MeSH
- Fluorouracil administration & dosage MeSH
- Antibodies, Monoclonal, Humanized pharmacokinetics therapeutic use MeSH
- Infusions, Intravenous MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Breast Neoplasms drug therapy chemistry pathology MeSH
- Neoadjuvant Therapy methods MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Receptor, ErbB-2 analysis MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Neoplasm Grading MeSH
- Infusions, Subcutaneous MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
This paper reviews an early clinical experience with anthracycline (epirubicin; Epi or doxorubicin; Dox) containing an N-(2-hydroyxypropyl)methacrylamide copolymer carrier targeted with autologous or commercial human immunoglobulin in six patients aged 28-55 suffering from therapy-resistant metastatic cancer. More than 100 biochemical, hematological and immunological parameters, including nine tumor markers, were tested in blood samples taken 24 h after the first and up to 10 months after the last application. The intravenous application proceeded without serious adverse or side effects and did not require hospitalization. Cardiotoxicity was not observed. Four of six monitored patients attained stabilization of disease (liver ultrasound scan and bone computer tomography) with a very good quality of life lasting from seven up to 18 months. Positive response to the treatment was, among others, evaluated as decreased CA 15-3 and CEA tumor markers. In three of five tested patients the serum level of C-reactive protein was temporarily increased 72 h after the treatment. A stable or elevated number of peripheral blood reticulocytes together with activation of natural killer (NK) cells and lymphokine-activated killer (LAK) cells supports the data previously obtained in experimental animals pointing to a dual role, i.e. the cytotoxic and immunomobilizing character of doxorubicin-HPMA conjugates.
- MeSH
- Acrylamides MeSH
- Drug Resistance, Neoplasm MeSH
- Adult MeSH
- Doxorubicin analogs & derivatives administration & dosage adverse effects therapeutic use MeSH
- Epirubicin administration & dosage adverse effects therapeutic use MeSH
- Hemangiosarcoma drug therapy MeSH
- Immunoglobulin G administration & dosage immunology MeSH
- Immunologic Factors administration & dosage immunology MeSH
- Immunoglobulins, Intravenous administration & dosage immunology MeSH
- Quality of Life MeSH
- Polymethacrylic Acids administration & dosage adverse effects therapeutic use MeSH
- Drug Delivery Systems MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Biomarkers, Tumor blood MeSH
- Breast Neoplasms drug therapy MeSH
- Drug Carriers chemistry MeSH
- Antibiotics, Antineoplastic administration & dosage adverse effects therapeutic use MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Rakovina žalúdka je stále veľkým medicínskym problémom a vedúcou príčinou úmrtí napriek celosvetovému poklesu v jej incidencii. Výsledky terapie sa zlepšili v Japonsku, Kórei a niektorých západných centrách najmä vďaka skorej detekcii ochorenia. Chirurgia dosahuje výborné výsledky dlhodobého prežívania najmä u skorého karcinómu žalúdka (EGC). Na západe má ale viac než 80 % pacientov v čase stanovenia diagnózy pokročilé ochorenie so zlou prognózou. Cieľom chirurgie je kompletné odstránenie nádoru (UICC-R0 resekcia), čo je jediná dokázaná efektívna terapeutická modalita a najdôležitejší prognostický faktor. Prognóza po chirurgickom zákroku je zlá. Neoadjuvantná chemoterapia je novou možnosťou pri lokálne pokročilom karcinóme žalúdka. Adjuvantná chemoradiácia sa ukazuje prínosnou u pacientov so suboptimálnou resekciou. Benefit adjuvantnej chemoterapie je veľmi malý. Neliečená rakovina žalúdka má medián prežívania iba 3 – 4 mesiace, tento sa dá zvýšiť kombinovanou chemoterapiou na 8 – 10 mesiacov so zlepšením kvality života. V súčasnosti neexistuje žiaden štandardný chemoterapeutický režim, ale režimy používajúce cisplatinu a 5-fluorouracil, ako epirubicín/cisplatina/fluorouracil (ECF) alebo docetaxel/cisplatina/fluorouracil (DCF) patria medzi najaktívnejšie. Novšie chemoterapeutiká ako irinotekan, oxaliplatina a taxány sa javia ako sľubné a sú skúšané spolu s biopreparátmi v klinických štúdiách.
Gastric cancer is still a major health problem and a leading cause of cancer mortality despite a worldwide decline in incidence. Primarily due to early detection of the disease, the results of treatment for gastric cancer have improved in Japan, Korea and several specialized Western centres. Surgery offers excellent long-term survival results for early gastric cancer (EGC). In the Western world, however more than 80 % of patients at diagnosis have an advanced gastric cancer with a poor prognosis. The aim of surgery is the complete removal of the tumour (UICC R0-resection), which is known to be the only proven, effective treatment modality and the most important treatment-related prognostic factor. The prognosis after surgical treatment of gastric cancer remains poor. Neoadjuvant chemotherapy is a rising option in locally advanced gastric cancer. Adjuvant chemoradiation has been shown to be beneficial in gastric cancer patients who have undergone suboptimal surgical resection. The benefits of adjuvant chemotherapy alone seem to be very small, Untreated metastatic gastric cancer is associated with a median survival of only 3 – 4 months, but this can be increased to 8 – 10 months, associated with improved quality of life, with combination chemotherapy. Currently, no standard combination chemotherapy regimen exists, although regimens utilizing both cisplatin and 5-fluorouracil, such as epirubicin/cisplatin/fluorouracil (ECF) or docetaxel/cisplatin/fluorouracil (DCF) are amongst the most active. Newer chemotherapeutic agents, including irinotecan, oxaliplatin and taxanes, show promising activity, and are currently being tested with biologics in clinical trials
- MeSH
- Chemotherapy, Adjuvant methods trends utilization MeSH
- Survival Analysis MeSH
- Cisplatin administration & dosage therapeutic use MeSH
- Epirubicin administration & dosage therapeutic use MeSH
- Fluorouracil administration & dosage therapeutic use MeSH
- Gastroscopy methods utilization MeSH
- Camptothecin analogs & derivatives administration & dosage therapeutic use MeSH
- Quality of Life MeSH
- Humans MeSH
- Stomach Neoplasms diagnosis epidemiology surgery MeSH
- Organoplatinum Compounds administration & dosage therapeutic use MeSH
- Review Literature as Topic MeSH
- Risk Factors MeSH
- Taxoids administration & dosage therapeutic use MeSH
- Check Tag
- Humans MeSH
