Pazopanib

Structural formula
General
Surname	Pazopanib
other names	5 - ((4 - ((2,3-dimethyl-2 H -indazole-6-yl) methylamino) -2-pyrimidinyl) amino) -2-methylbenzenesulfonamide
Molecular formula	C 21 H 23 N 7 O 2 S
External identifiers / databases
CAS number 444731-52-6 PubChem 10113978 ChemSpider 8289501 DrugBank DB06589 Wikidata Q7157043
Drug information
ATC code	L01 XE11
properties
Molar mass	437.517 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Pazopanib is a drug from the group of tyrosine kinase inhibitors . The substance to be taken orally was approved in the EU in 2010 for the treatment of advanced and / or metastatic renal cell carcinoma . In 2012, approval was extended for selected subtypes of advanced soft tissue sarcoma .

effect

The tyrosine kinase inhibitor inhibits important signal transduction pathways in the tumor cells and, on the other hand, prevents the formation of new blood vessels that supply the tumor. The effect occurs via the inhibition of several tyrosine kinases (VEGFR, PDGFR, KIT). The plasma half-life is 30 hours, which is why it is usually taken once a day, with some time after the meal.

Study situation

Renal cell carcinoma

In June 2010, pazopanib was approved by the European Medicines Agency (EMA) for the treatment of renal cell carcinoma in first-line therapy and for renal cell carcinoma patients who had previously received therapy with cytokines . Approval was based on the results of a 2: 1 randomized phase III study published in 2010 in which 435 patients with advanced renal cell carcinoma were treated with either 800 mg pazopanib daily or with placebo . The median progression-free survival of pazopanib-treated patients was 9.2 months (95% confidence interval CI: 7.4–12.9 months) compared to placebo patients (4.2 months; CI: 2.8–4 , 2) significantly longer. At the time of the analysis, the overall survival of the first group was also increased (21.2 months compared to 19.3 months), but the difference was not significant.

A study published in the New England Journal of Medicine in 2013 compared the older standard therapy sunitinib with pazopanib. 1,110 patients with metastatic clear cell renal cell carcinoma received either 800 mg pazopanib daily, or 50 mg sunitinib daily for 4 weeks, followed by a 2-week break. The study was designed as a non-inferiority study. The pazopanib patients at 8.4 months (95% CI: 8.3 to 10.9) compared to the sunitinib patients at 9.5 months (95% CI: 8.3 to 11.1) had a statistically no lower progression-free survival, which shows the equivalent effect. In terms of the spectrum of side effects, however, pazopanib was significantly better tolerated in all parameters examined.

Soft tissue sarcomas

The basis for approval for the treatment of soft tissue sarcomas was the so-called PALETTE therapy study published in 2012 . In this large, multinational study, 369 soft tissue sarcoma patients were randomized 2: 1 to receive either 800 mg pazopanib or placebo. The study was funded by GlaxoSmithKline . The median progression-free survival was 4.6 months (95% CI 3.7-4.8) in the pazopanib group versus 1.8 months (0.9-1.8) in the placebo group. For median overall survival , the data were 12.5 months (10.6–14.8) versus 10.7 months (8.7–12.8).

However, only patients with certain types of soft tissue sarcoma were included in the PALETTE study, which is why the effectiveness of pazopanib has only been shown for these subtypes. Patients with the following sarcoma types were excluded from this study: adipocytic sarcoma (all subtypes); all rhabdomyosarcomas that are not alveolar or pleomorphic; Dermatofibrosarcoma Protuberans ; inflammatory myofibroblastic sarcoma; malignant mesothelioma and mixed mesodermal tumors of the uterus. As a result of this study, pazopanib was approved by the European Medicines Agency ( EMA) for the treatment of adult patients with selected subtypes of advanced soft tissue sarcoma. Approval was granted for patients who had previously received chemotherapy for their metastatic disease or who had their disease progressing again within 12 months of (neo-) adjuvant therapy .

Contraindications

Pazopanib must not be administered in the case of hypersensitivity and severe liver dysfunction.

Side effects

Common undesirable side effects are indigestion (loss of appetite, abdominal pain, diarrhea , nausea , vomiting , taste disturbances), increase in liver enzymes , hypertension , fatigue and changes in hair color. The liver enzyme disorders appear obviously earlier than expected, which is why the manufacturer recommends more frequent and stricter controls of the liver function.

Interactions

As a substrate for CYP3A4 , pazopanib can interact with many other medicinal products.

Trade names

Pazopanib is available as film- coated tablets under the name Votrient . The usual daily dose is 800 mg once a day.

Web links

• Votrient (pazopanib) - Information from the drug commission of the German medical profession (PDF; 301 kB)
• Product information texts Votrient (pazopanib) (PDF; 497 kB)

Individual evidence

1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
2. ↑ New oncological drugs: pazopanib for the treatment of advanced renal cell carcinoma . In: The medicament letter . tape 45 , 2011 ( online ).
3. ↑ Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010; 28 (6): 1061-8. doi : 10.1200 / JCO.2009.23.9764
4. ↑ Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U , Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2013; 369 (8): 722-31. doi : 10.1056 / NEJMoa1303989
5. ↑ van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M , Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group: Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2012; 379 (9829): 1879-86. doi : 10.1016 / S0140-6736 (12) 60651-5 .
6. ↑ SUMMARY OF PRODUCT CHARACTERISTICS: Votrient. (PDF) EMA, accessed on July 13, 2017 . 
7. ↑ BfArM: Information letter on Votrient® (pazopanib) , July 30, 2013.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !