The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.

• Klíčová slova
• ALL, acute lymphoblastic leukemia, AML, acute myeloid leukemia, CML, chronic myeloid leukemia, DAMP, damage-associated molecular pattern, EGFR, epidermal growth factor receptor, EOX, epirubicin plus oxaliplatin plus capecitabine, ER, endoplasmic reticulum, FDA, Food and Drug Administration, FOLFIRINOX, folinic acid plus 5-fluorouracil plus irinotecan plus oxaliplatin, FOLFOX, folinic acid plus 5-fluorouracil plus oxaliplatin, GEMOX, gemcitabine plus oxaliplatin, GM-CSF, granulocyte-macrophage colony-stimulating factor, HCC, hepatocellular carcinoma, ICD, immunogenic cell death, MM, multiple myeloma, NHL, non-Hodgkin's lymphoma, NSCLC, non-small cell lung carcinoma, TACE, transcatheter arterial chemoembolization, XELOX, capecitabine plus oxaliplatin, antigen-presenting cell, autophagy, damage-associated molecular pattern, dendritic cell, endoplasmic reticulum stress, mAb, monoclonal antibody, type I interferon,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]). PATIENTS AND METHODS: Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period. RESULTS: A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300). CONCLUSION: Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.

• Klíčová slova
• Chemotherapy, Febrile neutropenia, Objective response rate, Overall survival, Progression-free survival,
• MeSH
• bevacizumab aplikace a dávkování   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• febrilní neutropenie chemicky indukované   epidemiologie   prevence a kontrola   MeSH
• filgrastim aplikace a dávkování   MeSH
• fluoruracil aplikace a dávkování   škodlivé účinky   MeSH
• incidence MeSH
• kamptothecin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• kolorektální nádory farmakoterapie   patologie   MeSH
• leukovorin aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• následné studie MeSH
• organoplatinové sloučeniny aplikace a dávkování   škodlivé účinky   MeSH
• polyethylenglykoly aplikace a dávkování   MeSH
• přežití bez známek nemoci MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor A antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý 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
• Názvy látek
• bevacizumab MeSH
• filgrastim MeSH
• fluoruracil MeSH
• kamptothecin MeSH
• leukovorin MeSH
• organoplatinové sloučeniny MeSH
• pegfilgrastim MeSH Prohlížeč
• polyethylenglykoly MeSH
• vaskulární endoteliální růstový faktor A MeSH

BACKGROUND: The aim of the present retrospective study was to analyze clinical outcome and risk factors associated with treatment outcomes according to KRAS status in patient with metastatic colorectal cancer (mCRC) treated with bevacizumab (bev) plus chemotherapy in the first-line setting. METHODS: We performed observational study on 1622 patients with mCRC treated with bev plus oxaliplatin- or irinotecan-based chemotherapy, and correlated treatment outcomes with KRAS mutation status. The primary endpoint was progression-free survival (PFS) and additionally overall survival (OS). Adverse events of bevacizumab and risk factors including location of metastases were evaluated. RESULTS: Mutation in KRAS was present in 40.6% of mCRC cases. The median PFS in patients with wild-type KRAS (wtKRAS) vs mutant KRAS was 11.5 vs 11.4 months, respectively. The median OS was 30.7 vs 28.4 months (p = 0.312). Patients with KRAS mutation had lung metastases more frequently than wtKRAS individuals (32.0% vs 23.8%; p = 0.001). We observed no difference in clinical outcome between hepatic and extrahepatic metastatic disease. CONCLUSION: KRAS mutation does not interfere with clinical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC patients.

• MeSH
• bevacizumab aplikace a dávkování   škodlivé účinky   MeSH
• capecitabinum MeSH
• deoxycytidin analogy a deriváty   terapeutické užití   MeSH
• dospělí MeSH
• fluoruracil analogy a deriváty   terapeutické užití   MeSH
• irinotekan MeSH
• kamptothecin aplikace a dávkování   analogy a deriváty   terapeutické užití   MeSH
• kolorektální nádory genetika   patologie   MeSH
• leukovorin terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• mutace MeSH
• nádory jater farmakoterapie   genetika   sekundární   MeSH
• nádory plic farmakoterapie   genetika   sekundární   MeSH
• organoplatinové sloučeniny aplikace a dávkování   terapeutické užití   MeSH
• oxalacetáty MeSH
• oxaliplatin MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny genetika   MeSH
• Ras proteiny genetika   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bevacizumab MeSH
• capecitabinum MeSH
• deoxycytidin MeSH
• fluoruracil MeSH
• irinotekan MeSH
• kamptothecin MeSH
• KRAS protein, human MeSH Prohlížeč
• leukovorin MeSH
• organoplatinové sloučeniny MeSH
• oxalacetáty MeSH
• oxaliplatin MeSH
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny MeSH
• Ras proteiny MeSH