Vismodegib je perorálně dostupný inhibitor signální dráhy Hedgehog. Je indikován u pacientů s metastatickým nebo lokálně pokročilým bazocelulárním karcinomem, jenž recidivoval po předchozím chirurgickém výkonu nebo nebyl vhodný k chirurgické léčbě ani k radioterapii. Podává se v dávce 150 mg 1x denně. Nežádoucí účinky v registrační studii ERIVANCE se vyskytly u více než 30 % pacientů.
Vismodegib is an orally available hedgehog-signal (Hedgehog signalling pathway) inhibitor. It is indicated in patients with metastatic or locally advanced basal cell carcinoma that has recurred after previous surgical procedure, or was not suitable for surgical treatment or radiotherapy. It is administered as 150 mg once daily. Undesirable effects observed in the pre-approval ERIVANCE study occurred in more than 30% of the patients.
- Keywords
- vismodegib (Erivedge),
- MeSH
- Anilides pharmacology therapeutic use MeSH
- Carcinoma, Basal Cell * drug therapy therapy MeSH
- Drug Evaluation statistics & numerical data MeSH
- Drug Prescriptions MeSH
- Humans MeSH
- Multicenter Studies as Topic statistics & numerical data MeSH
- Antineoplastic Agents administration & dosage pharmacokinetics pharmacology contraindications adverse effects therapeutic use MeSH
- Pyridines pharmacology therapeutic use MeSH
- Signal Transduction drug effects MeSH
- Pregnancy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
Bazaliom je nejčastější maligní kožní nádor a jeho incidence se stále zvyšuje. Léčba bazaliomu zahrnuje chirurgii, radioterapii, kryoterapii, fotodynamickou léčbu a lokální aplikaci imiquimodu, ale v případech pokročilých a metastazujících bazaliomů nejsou tyto metody účinné. Aktivace signální dráhy Hedgehog (HH) způsobuje proliferaci buněk a stimuluje nádorové kmenové buňky. Bylo prokázáno, že signální dráha je aktivní u téměř všech bazaliomů. Vismodegib je první lék zaměřený na signální dráhu HH a je účinný v léčbě pokročilého a metastazujícího bazaliomu. Schválení vismodegibu lékovými autoritami Food and Drug Administration i European Medicines Agency je velmi důležitým krokem v léčbě pokročilého bazaliomu.
Basal cell carcinoma is the most common skin cancer and the incidences of it are still rising. The treatment of BCC involves surgery, radiotherapy, cryosurgery, photodynamic therapy and topical therapy with imiquimod, but in cases of advanced or metastatic basal cell carcinoma these modalities are not helpful. The activation of Hedgehog (HH) pathway causes cellular proliferation and the stimulation of cancer stem cells. It was found that the HH pathway is activated in almost all basal cell carcinomas. Vismodegib is the first drug that targets the HH pathway and is effective in the treatment of advanced and metastatic BCC. The approval of vismodegib by the health authorities Food and Drug Administration and European Medicines Agency is very important step in the treatment of advanced BCC.
- MeSH
- Anilides administration & dosage adverse effects therapeutic use MeSH
- Carcinoma, Basal Cell * drug therapy pathology MeSH
- Clinical Trials, Phase I as Topic MeSH
- Clinical Trials, Phase II as Topic MeSH
- Humans MeSH
- Neoplasm Metastasis drug therapy MeSH
- Hedgehog Proteins * drug effects MeSH
- Pyridines administration & dosage adverse effects therapeutic use MeSH
- Recurrence MeSH
- Signal Transduction drug effects MeSH
- Pregnancy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
Bazaliom je nejčastější nemelanomový kožní nádor vycházející z bazálních buněk epidermis, charakterizovaný pomalým a destruktivním růstem. Nejčastější terapeutickou metodou je chirurgická excize. K ostatním terapeutickým možnostem patří radioterapie, aplikace imiquimodu, 5-fluorouracilu, kyretáž, elektrokauterizace, kryoterapie, ablace laserem, fotodynamická léčba a systémová terapie hedgehog inhibitory. Kazuistika popisuje případ pacienta s recidivujícím infiltrativním bazaliomem na čele vpravo, léčeného chirurgickou excizí, radioterapií a cílenou systémovou léčbou - vismodegib.
Basal cell carcinoma is the most common form of nonmelanoma skin cancer that arises from basal cells, characterized by slow and destruct growth. The most often terapeutic option is surgical excision. Other options include radiotherapy, application of imiquimod, 5-fluoruracil, curettage, electrocautery, cryotherapy, laser ablation, photodynamic therapy and systemic therapy by the hedgehog inhibitors. Case report describe male patient with recurrent infiltrative basal cell carcinoma located at the forehead on the right, treated by surgical excision, radiotherapy and targeted systemic therapy - vismodegib.
- Keywords
- vismodegib,
- MeSH
- Carcinoma, Basal Cell * drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Hedgehog Proteins antagonists & inhibitors MeSH
- Antineoplastic Agents therapeutic use MeSH
- Aged MeSH
- Signal Transduction drug effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
Vismodegib je nízkomolekulární inhibitor tzv. hedgehog dráhy, která reguluje buněčný růst. Pokud dojde k aktivaci této dráhy v dospělosti, objevují se některá nádorová onemocnění, a to zvláště kožní bazaliom. Autoři uvádějí případ 75leté pacientky s rozsáhlým, recidivujícím, inoperabilním bazocelulárním karcinomem, u kterého byly vyčerpané ostatní léčebné možnosti a šestiměsíční podávání vismodegibu vedlo ke zhojení nádoru. Klíčová slova: bazaliom – úspěšná léčba vismodegibem
Vismodegib is a low-molecular inhibitor of hedhe-hog signaling pathway that regulates cell growth. Its activation in adults leads to formation of some tumours, especially, basal cell carcinoma. Authors describe a case of 75-year old patient with unsuccessfully treated advanced, recurrent and inoperable basal cell carcinoma. The tumour healed after six months treatment with vismodegib. Key words: basal cell cacinoma – successful treatment with vismodegib
- Keywords
- vismodegib,
- MeSH
- Medical History Taking MeSH
- Anilides adverse effects therapeutic use MeSH
- Carcinoma, Basal Cell * diagnosis drug therapy pathology MeSH
- Biopsy MeSH
- Humans MeSH
- Pyridines adverse effects therapeutic use MeSH
- Recurrence MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Anilides pharmacokinetics pharmacology therapeutic use MeSH
- Molecular Targeted Therapy MeSH
- Clinical Trials, Phase II as Topic MeSH
- Humans MeSH
- Neoplasms drug therapy MeSH
- Antineoplastic Agents pharmacokinetics pharmacology therapeutic use MeSH
- Pyridines pharmacokinetics pharmacology therapeutic use MeSH
- Receptors, G-Protein-Coupled antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
- Keywords
- vismodegib, Erivedge,
- MeSH
- Anilides adverse effects therapeutic use MeSH
- Carcinoma, Basal Cell * drug therapy MeSH
- Remission Induction MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy MeSH
- Eyelid Neoplasms * drug therapy MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Pyridines adverse effects therapeutic use MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Keywords
- ERIVANCE BCC,
- MeSH
- Anilides * administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Carcinoma, Basal Cell * drug therapy MeSH
- Humans MeSH
- Skin Neoplasms drug therapy MeSH
- Hedgehog Proteins antagonists & inhibitors MeSH
- Antineoplastic Agents administration & dosage adverse effects therapeutic use MeSH
- Pyridines * administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Signal Transduction drug effects MeSH
- Check Tag
- Humans MeSH
- MeSH
- Carcinoma, Basal Cell * drug therapy therapy MeSH
- Adult MeSH
- Clinical Trials as Topic MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis drug therapy therapy MeSH
- Skin Neoplasms drug therapy therapy MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Hedgehog Proteins * antagonists & inhibitors pharmacology therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
BACKGROUND: The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented. PATIENTS AND METHODS: Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points. RESULTS: Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC. CONCLUSIONS: The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. CLINICALTRIALS.GOV: NCT01367665.
- MeSH
- Anilides administration & dosage adverse effects MeSH
- Administration, Oral MeSH
- Carcinoma, Basal Cell drug therapy mortality secondary MeSH
- Time Factors MeSH
- Adult MeSH
- Kaplan-Meier Estimate MeSH
- Creatine Kinase blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Disease-Free Survival MeSH
- Disease Progression MeSH
- Antineoplastic Agents administration & dosage adverse effects MeSH
- Pyridines administration & dosage adverse effects MeSH
- Drug Administration Schedule MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Spasm chemically induced MeSH
- Basal Cell Nevus Syndrome drug therapy mortality pathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
