Pazopanib
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| ID | DRUG-PAZOPANIB |
|---|---|
| Tipo | Fármaco |
| Alegais | VotrientПазопаніб |
| Estado | reviewed 2026-05-07 | pending_clinical_signoff |
| Doenças | DIS-SOFT-TISSUE-SARCOMA |
| Fontes | SRC-COMPARZ-MOTZER-2013 SRC-ESMO-RCC-2024 SRC-NCCN-KIDNEY-2025 SRC-PALETTE-VAN-DER-GRAAF-2012 SRC-VEG105192-STERNBERG-2010 |
Fatos sobre as drogas
| Classe | Inibidor da tirosina quinase oral multi-alvo (VEGFR-1/2/3, PDGFR-α/β, c-KIT) |
|---|---|
| Mecanismo | Orally bioavailable small-molecule multi-kinase inhibitor of vascular endothelial growth factor receptors VEGFR-1, VEGFR-2, and VEGFR-3, platelet-derived growth factor receptors PDGFR-α and PDGFR-β, and stem-cell factor receptor c-KIT. Antiangiogenic mechanism: inhibition of VEGFR-driven endothelial proliferation, migration, and tube formation starves the tumor microvasculature; PDGFR blockade additionally targets pericyte recruitment and stromal support. Activity in clear-cell renal cell carcinoma (driven by VHL-loss / HIF-2α / VEGF axis) and in soft tissue sarcoma (with VEGFR / PDGFR / c-KIT signaling contributing to tumor angiogenesis and proliferation). Significant CYP3A4 substrate with substantial drug-drug-interaction potential; requires fasting administration (food roughly doubles AUC). |
| Dose típica | Standard adult dose: 800 mg PO once daily continuous, taken on an empty stomach (≥1 hour before or ≥2 hours after a meal — food significantly increases exposure and toxicity risk). Dose reductions to 400 mg then 200 mg for grade 3-4 toxicity or hepatic AE per labelling. Treatment continued until disease progression or unacceptable toxicity. Hepatic monitoring schedule (per FDA boxed warning): LFTs at baseline, weeks 3, 5, 7, 9, then monthly through month 4, then periodically. Hold for ALT >3× ULN; permanently discontinue for ALT >8× ULN or concurrent ALT >3× ULN with bilirubin >2× ULN. Dose reduction to 200 mg recommended for moderate hepatic impairment; not recommended in severe hepatic im... |
| Ucrânia registada | Verdade |
| NSZU reembolsado | Falso |
| Ucrânia verificada pela última vez | 2026-05-07 |
Avisos
- Hepatotoxicidade grave e fatal — elevações da ALT > 3× LSN em ~20%, > 8× LNN em ~10%; ocorreram insuficiência hepática fatal rara. Esquema de monitorização do TFT (base de referência, semanas 3/5/7/9, mensal a 4 meses, e, em seguida, periodicamente)
Notas
First-generation multi-kinase TKI (originally GlaxoSmithKline, development code GW786034; transferred to Novartis 2015 acquisition of GSK oncology portfolio). FDA-approved Oct 2009 for advanced RCC on the basis of VEG105192 (Sternberg et al. JCO 2010 — pazopanib vs placebo in treatment-naive or cytokine-pretreated mRCC: mPFS 9.2 vs 4.2 mo, HR 0.46). Subsequently FDA-approved April 2012 for advanced STS (excluding GIST and adipocytic sarcoma) post-chemo on the basis of PALETTE phase 3 (van der Graaf et al. Lancet 2012 — pazopanib vs placebo: mPFS 4.6 vs 1.6 mo, HR 0.35). COMPARZ phase 3 (Motzer et al. NEJM 2013) demonstrated non-inferiority of pazopanib vs sunitinib for mPFS in 1L mRCC (8.4 vs 9.5 mo) with a different toxicity profile — less fatigue and hand-foot syndrome with pazopanib but more hepatotoxicity. PISCES patient-preference study (Escudier et al. JCO 2014) showed 70% of patients preferred pazopanib vs sunitinib on QoL grounds. Pazopanib remains an acceptable NCCN single-agent TKI option in 1L mRCC favorable-risk and as a chemo-free alternative in poor-PS patients where ICI combination is contraindicated. Modern 1L ccRCC standard is ICI-based combination (pembrolizumab+...
Usado por
Esquema terapêutico
REG-PAZOPANIB-RCC- Pazopanib (RCC)REG-PAZOPANIB-STS- Pazopanib (sarcoma de tecidos moles, 2L)