pazopanib
Regulatory sources consulted
Approved indications
- Adults with advanced renal-cell carcinoma as first-line treatment or after prior cytokine therapy; or selected subtypes of advanced soft-tissue sarcoma after chemotherapy for metastatic disease or progression within 12 months after neoadjuvant or adjuvant therapy. Efficacy has not been demonstrated in adipocytic sarcoma or GIST.
Contraindications
Absolute
- Hypersensitivity to pazopanib or excipients.
Clinical warnings
- It can cause severe or fatal hepatotoxicity. Monitor liver tests at baseline and regularly; withhold, reduce, or discontinue according to ALT, bilirubin, and course, with weekly monitoring when indicated. — OpenFDA, set_id 115eb5bb-1403-fb3d-e063-6394a90ad320
- Monitor QT/electrolytes, cardiac dysfunction/LVEF, hypertension, bleeding, arterial or venous thrombosis, thrombotic microangiopathy, gastrointestinal perforation or fistula, pneumothorax, proteinuria, tumor lysis syndrome, and wound healing. Withhold or discontinue for severe toxicity. — CIMA/AEMPS, ficha técnica 90228
- Withhold pazopanib for at least 1 week before elective surgery. After major surgery, do not restart for at least 2 weeks and until adequate wound healing. — OpenFDA, set_id 115eb5bb-1403-fb3d-e063-6394a90ad320
Drug interactions
- HighStrong CYP3A4/P-gp/BCRP inhibitors
Mechanism: They increase pazopanib exposure.
Recommendation: Avoid; if unavoidable, reduce pazopanib to 400 mg/day and monitor toxicity.
CIMA/AEMPS, ficha técnica 90228
- HighStrong CYP3A4 inducers
Mechanism: They reduce pazopanib exposure.
Recommendation: Select an alternative; pazopanib is not recommended if chronic use is unavoidable.
OpenFDA, set_id 115eb5bb-1403-fb3d-e063-6394a90ad320
- HighSimvastatin
Mechanism: It increases the risk of ALT elevation.
Recommendation: Monitor ALT weekly and discontinue simvastatin if elevation occurs.
OpenFDA, set_id 115eb5bb-1403-fb3d-e063-6394a90ad320
- HighGastric pH-elevating medicines
Mechanism: They reduce exposure and may decrease pazopanib efficacy.
Recommendation: Avoid PPIs and H2 antagonists. If an acid reducer cannot be avoided, prefer a short-acting antacid and separate it from pazopanib by several hours.
OpenFDA, set_id 115eb5bb-1403-fb3d-e063-6394a90ad320
Adverse events
Common (≥1%)
diarrhea · hair-color changes · skin hypopigmentation · rash · hypertension · nausea · headache · fatigue · anorexia · vomiting · dysgeusia · stomatitis · weight loss · increased ALT or AST
Pregnancy and lactation
Avoid during pregnancy unless clinically required and verify pregnancy before starting. Women must use adequate contraception and men must use condoms during treatment and for at least 2 weeks afterward. Do not breastfeed during treatment or for 2 weeks afterward.
Recent literature (PubMed)
Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL). To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs). We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs. We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable. All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were c
Clinical trial enrollment should be actively encouraged in all patients diagnosed with advanced, surgically unresectable chondrosarcoma (CS) due to the lack of consensus treatment recommendations. In the absence of an appropriate clinical trial, treatments are determined based on histologic subtype of CS with consideration given to targetable mutations (i.e., IDH1). Conventional CS is inherently resistant to cytotoxic chemotherapy and patients may benefit from antiangiogenic therapy including off-label use of pazopanib. Individuals harboring an IDH1 mutation may derive clinical benefit from ivosidenib, an IDH1 inhibitor. Upon progression and with functional status permitting, alternative options include mTOR inhibitors (sirolimus, temsirolimus) or other tyrosine kinase inhibitors (dasatinib), though no clear sequencing data exists. For dedifferentiated CS, conventional chemotherapies with osteosarcoma-like regimens are upfront options although prospective data is limited with minimal overall benefit. Alternative treatment options include immunotherapy with pembrolizumab or ivosidenib in IDH1-mutant, dedifferentiated CS, but questionable efficacy was observed in small sample sizes with either approach. In mesenchymal CS, treatment with Ewing sarcoma-like chemotherapy regimens may be considered, although data supporting its use is even more limited given its rarity. Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins. The most common clinical manifestation is recurrent nosebleeds (epistaxis) beginning on average at age 12 years. Telangiectases (small AVMs) are characteristically found on the lips, tongue, buccal and gastrointestinal (GI) mucosa, fingers, and nose. The appearance of telangiectases is generally later than epistaxis but may be during childhood. Large AVMs occur most often in the lungs, liver
Das kutane Angiosarkom (CAS) ist ein hochaggressiver maligner Tumor mit schlechter Prognose. Das primäre, spontane CAS (pCAS) und das sekundäre, mit einer Bestrahlung oder einem Lymphödem assoziierte CAS (sCAS) unterscheiden sich klinisch sowie molekular. Die Amplifikation/Überexpression von Myc ist ein charakteristisches, wenn auch nicht ausschließliches Merkmal von sCAS, während der Verlust von TP53 selektiv bei pCAS vorkommt. Detaillierte molekulare Analysen mit modernen Multi-Omics-Ansätzen haben gezeigt, dass sowohl pCAS als auch sCAS eine erhebliche molekulare Heterogenität aufweisen. Die betroffenen Gene und ihre molekularen Regulatoren sind mögliche therapeutische Zielstrukturen. Darüber hinaus kann das pCAS in Cluster mit hoher Mutationsrate und/oder ausgeprägten Entzündungssignaturen eingeteilt werden, die als Grundlage für die künftige Stratifizierung von pCAS-Patienten in immuntherapeutischen klinischen Studien dienen können. Während die Aufklärung der der Erkrankung zugrunde liegenden molekularen Veränderungen zügig voranschreitet, verläuft die Entwicklung daraus abgeleiteter neuer Therapien für das CAS jedoch bisher eher langsam. Dennoch wurden einige über die Standardtherapien wie Operation und Radiochemotherapie hinausgehende klinische Studien zu neuen Behandlungsmöglichkeiten initiiert. Dazu gehören zielgerichtete Therapien gegen VEGF und VEGFR1-3 wie Bevacizumab und Pazopanib, sowie β-Adrenozeptorenblocker wie Propranolol. Derzeit werden auch Immuntherapien entwickelt, unter anderem unter Verwendung der Immuncheckpoint-Inhibitoren Pembrolizumab und Nivolumab sowie des Anti-RANKL-Antikörper Denosumab.