pazopanib and Hypertension

Cervical cancer ranks as the fourth leading cause of death from cancer in women. Historically, women with metastatic or recurrent cervical cancer have had limited treatment options. New anti-angiogenesis therapies, such as vascular endothelial growth factor (VEGF) targeting agents, offer an alternative strategy to conventional chemotherapy; they act by inhibiting the growth of new blood vessels, thereby restricting tumour growth by blocking the blood supply.. To assess the benefits and harms of VEGF targeting agents in the management of persistent, recurrent, or metastatic cervical cancer.. We performed searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, online registers of clinical trials, and abstracts of scientific meetings up until 27 May 2020.. We examined randomised controlled trials (RCTs) that evaluated the use of VEGF targeting agents alone or in combination with conventional chemotherapy or other VEGF targeting agents.. Three review authors independently screened the results of search strategies, extracted data, assessed risk of bias, and analysed data according to the standard methods expected by Cochrane. The certainty of evidence was assessed via the GRADE approach.. A total of 1634 records were identified. From these, we identified four studies with a total of 808 participants for inclusion. We also identified two studies that were awaiting classification and nine ongoing studies. Bevacizumab plus chemotherapy versus chemotherapy Treatment with bevacizumab plus chemotherapy may result in lower risk of death compared to chemotherapy alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.62 to 0.95; 1 study, 452 participants; low-certainty evidence). However, there are probably more specific adverse events when compared to chemotherapy alone, including gastrointestinal perforations or fistulae (risk ratio (RR) 18.00, 95% CI 2.42 to 133.67; 1 study, 440 participants; moderate-certainty evidence); serious thromboembolic events (RR 4.5, 95% CI 1.55 to 13.08; 1 study, 440 participants; moderate-certainty evidence); and hypertension (RR 13.75, 95% CI 5.07 to 37.29; 1 study, 440 participants; moderate-certainty evidence). There may also be a higher incidence of serious haemorrhage (RR 5.00, 95% CI 1.11 to 22.56; 1 study, 440 participants; low-certainty evidence). In addition, the incidence of serious adverse events is probably higher (RR 1.44, 95% CI 1.16 to 1.79; 1 study, 439 participants; moderate-certainty evidence). The incremental cost-effectiveness ratio was USD 295,164 per quality-adjusted life-year (1 study, 452 participants; low-certainty evidence). Cediranib plus chemotherapy versus chemotherapy Treatment with cediranib plus chemotherapy may or may not result in similar risk of death when compared to chemotherapy alone (HR 0.94, 95% CI 0.53 to 1.65; 1 study, 69 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 3.27, 95% CI 0.14 to 77.57; 1 study, 67 participants; very low-certainty evidence); serious haemorrhage (RR 5.45, 95% CI 0.27 to 109.49; 1 study, 67 participants; very low-certainty evidence); serious thromboembolic events (RR 3.41, 95% CI 0.14 to 80.59; 1 study, 60 participants; very low-certainty evidence); and serious hypertension (RR 0.36, 95% CI 0.02 to 8.62; 1 study, 67 participants; very low-certainty evidence). In addition, there may or may not be a similar incidence of serious adverse events compared to chemotherapy alone (RR 1.15, 95% CI 0.75 to 1.78; 1 study, 67 participants; low-certainty evidence). Apatinib plus chemotherapy or chemotherapy/brachytherapy versus chemot. We found low-certainty evidence in favour of the use of bevacizumab plus chemotherapy. However, bevacizumab probably increases specific adverse events (gastrointestinal perforations or fistulae, thromboembolic events, hypertension) and serious adverse events. We found low-certainty evidence that does not support the use of cediranib plus chemotherapy, apatinib plus chemotherapy, apatinib plus chemotherapy/brachytherapy, or pazopanib monotherapy. We found low-certainty evidence suggesting that pazopanib plus lapatinib worsens outcomes. The VEGF inhibitors apatinib and pazopanib may increase the probability of hypertension events.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antineoplastic Agents; Bevacizumab; Bias; Brachytherapy; Combined Modality Therapy; Confidence Intervals; Female; Gastric Fistula; Gastrointestinal Hemorrhage; Humans; Hypertension; Indazoles; Intestinal Fistula; Intestinal Perforation; Lapatinib; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Pyridines; Pyrimidines; Quality of Life; Quinazolines; Randomized Controlled Trials as Topic; Sulfonamides; Thromboembolism; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A; Young Adult

Pazopanib is a protein tyrosine kinase inhibitor that limits tumor growth through angiogenesis inhibition. The use of other protein tyrosine kinase inhibitors, specifically sunitinib, within non-clear cell renal cell carcinoma (nccRCC) has led to increased survival with a decreased adverse event profile. The data for the treatment of nccRCC is limited, with most studies evaluating the use of sunitinib. Therefore, the evaluation of pazopanib is of particular clinical interest in the treatment of nccRCC. The objective of this systematic review was to assess the efficacy and safety of pazopanib for nccRCC. PubMed (1946 to April 2019) and Embase (1947 to April 2019) were queried using the search term combination: protein tyrosine kinase inhibitor or pazopanib and non clear cell renal cell carcinoma or non-clear cell renal cell carcinoma. Studies evaluating clinical outcomes of pazopanib for nccRCC were included, represented by 3 retrospective cohort studies and 1 single-arm, open-label prospective study. In patients with advanced or metastatic nccRCC, treatment with pazopanib resulted in positive effects for multiple markers of efficacy, including progression-free survival, overall survival, and objective response rates. The median duration of follow-up ranged from 11.8 months to 24.4 months. Pazopanib was well-tolerated in most studies. The most commonly reported adverse events were fatigue, diarrhea, and hypertension. Pazopanib appears to be an effective and safe option for the treatment of advanced or metastatic nccRCC. Future investigation with larger randomized controlled trials is warranted to further define the role of pazopanib in patients with nccRCC.

Topics: Angiogenesis Inhibitors; Carcinoma, Renal Cell; Clinical Trials as Topic; Diarrhea; Fatigue; Humans; Hypertension; Indazoles; Kidney Neoplasms; Progression-Free Survival; Protein Kinase Inhibitors; Pyrimidines; Sulfonamides

As precision medicine has become a focus in oncology in recent years, many targeted and biologic agents are being used along with or in place of traditional cytotoxic chemotherapy. As these drugs have been developed and some have received FDA approval, we have gained substantial data about the adverse event profiles. However, the management and approach to the toxicities incurred and subsequent complications are often not well understood, especially for physicians who have a varied clinical practice. The purpose of this review is to provide an overview of the frequency and types of adverse events and appropriate management steps when prescribing modern targeted therapies for gynecologic cancers in the classes of anti-angiogenic agents, poly-ADP-ribose polymerase (PARP) inhibitors, and immunotherapy drugs.

Topics: Anemia; Angiogenesis Inhibitors; Antineoplastic Agents, Immunological; Autoimmune Diseases; Bevacizumab; Diarrhea; Epistaxis; Fatigue; Female; Genital Neoplasms, Female; Headache; Hemorrhage; Humans; Hypertension; Indazoles; Intestinal Perforation; Molecular Targeted Therapy; Nausea; Neutropenia; Poly(ADP-ribose) Polymerase Inhibitors; Precision Medicine; Proteinuria; Pyrimidines; Risk Assessment; Sulfonamides; Vomiting; Water-Electrolyte Imbalance

Medullary thyroid cancer (MTC) is a rare malignancy with a poor prognosis. First line therapy is surgery, which is the only curative method of the disease. However, in non-operable cases or with tumor progression and metastases, a systemic treatment is necessary. This form of cancer is often insensitive to conventional chemotherapy, but the use of tyrosine kinase inhibitors (TKIs), such as pazopanib, cabozantinib, and vandetanib, has shown promising results with an increase in progression-free survival and prolonged lifetime. Therefore, we focused on the pharmacological characteristics of TKIs, their mechanism of action, their application as a secondary treatment option for MTC, their efficacy as a cancer drug treatment, and reviewed the ongoing clinical trials. TKIs also act systemically causing various adverse events (AEs). One common AE of this treatment is hypertension, known to be associated with cardiovascular disease and can therefore potentially worsen the well-being of the treated patients. The available treatment strategies of drug-induced hypertension were discussed. The mechanism behind the development of hypertension is still unclear. Therefore, the treatment of this AE remains symptomatic. Thus, future studies are necessary to investigate the link between tumor growth inhibition and hypertension. In addition, optimized, individual treatment strategies should be implemented.

Topics: Anilides; Carcinoma, Neuroendocrine; Cardiotoxicity; Humans; Hypertension; Indazoles; Piperidines; Protein Kinase Inhibitors; Pyridines; Pyrimidines; Quinazolines; Sulfonamides; Thyroid Neoplasms

To gain a better understanding of the overall incidence and risk of hypertension in cancer patients who receive pazopanib and to compare the differences in incidence among sorafenib, sunitinib, and pazopanib.. Several databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned single drug pazopanib 800 mg/day with data on hypertension available. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.. A total of 1,651 patients with a variety of solid tumors from 13 clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade hypertension in cancer patients were 35.9 % (95 % CI 31.5-40.6 %) and 6.5 % (95 % CI 5.2-8.0 %), respectively. The use of pazopanib was associated with an increased risk of developing all-grade (RR 4.97, 95 % CI 3.38-7.30, p < 0.001) and high-grade hypertension (RR 2.87, 95 % CI 1.16-7.12, p = 0.023). Additionally, there was no significant difference in the incidence of all-grade (RR 1.21, 95 % CI 0.96-1.53, p = 0.11) and high-grade hypertension (RR 1.29, 95 % CI 0.80-2.07, p = 0.30) between RCC and non-RCC patients. Interestingly, the risk of all-grade hypertension with pazopanib was substantially higher than sorafenib (RR 1.99; 95 % CI 1.73-2.29, p = 0.00) and sunitinib (RR 2.20; 95 % CI 1.92-2.52, p = 0.00), while the risk of pazopanib-induced high-grade hypertension was similar to sorafenib (RR 0.98; 95 % CI 0.75-1.30, p = 0.90) and sunitinib (RR 0.81; 95 % CI 0.62-1.06, p = 0.12).. The use of pazopanib is associated with a significantly increased risk of developing hypertension. Close monitoring and appropriate managements are recommended during the therapy. Future studies are still needed to investigate the risk reduction and possible use of pazopanib in selected patients.

Topics: Angiogenesis Inhibitors; Clinical Trials as Topic; Humans; Hypertension; Incidence; Indazoles; Neoplasms; Prospective Studies; Publication Bias; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Risk; Sulfonamides

[Figure: see text].

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Cardiac Output; Endothelium, Vascular; Female; Hemodynamics; Humans; Hypertension; Indazoles; Male; Middle Aged; Neoplasms; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Sulfonamides; Vascular Resistance; Vascular Stiffness

Use of angiotensin system inhibitors (ASIs; angiotensin receptor blockers or angiotensin-converting enzyme inhibitors) has been reported to be associated with improved survival in metastatic renal cell carcinoma (mRCC), particularly when used with vascular endothelial growth factor-targeted therapies. This study was a secondary pooled analysis of two Phase III randomized controlled trials (RCTs) of patients with mRCC: NCT00334282 comparing pazopanib to placebo and NCT00720941 comparing pazopanib to sunitinib. ASI users were defined as patients using an ASI at baseline. Association with overall survival (OS; primary outcome) and progression-free survival (PFS) was evaluated using Cox proportional hazards regression. The association was adjusted in multivariable analysis for baseline systolic blood pressure (SBP), use of other antihypertensive drugs and prognostic factors comprising the Heng risk criteria for mRCC. Of 1,545 patients pooled from the two RCTs, 649 (42%) were using one or more antihypertensive drugs at baseline, 385 (59%) of which were using an ASI. In the multivariable analysis of patients using pazopanib or sunitinib, no significant association was observed between baseline ASI use and OS (hazard ratio [HR] 0.97 [95% confidence interval (CI) 0.80-1.18], p = 0.80) or PFS (HR 0.88 [95% CI 0.73-1.06], p = 0.17). Exploratory subgroup analysis of NCT00720941 highlighted that the effect of baseline ASI use on OS may differ between patients treated with sunitinib and pazopanib. In conclusion, use of ASIs at baseline was not a significant independent prognostic factor for improved survival in a pooled analysis of mRCC patients treated with pazopanib or sunitinib.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antineoplastic Agents; Carcinoma, Renal Cell; Disease-Free Survival; Female; Humans; Hypertension; Indazoles; Indoles; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Middle Aged; Prognosis; Proportional Hazards Models; Pyrimidines; Pyrroles; Sulfonamides; Sunitinib; Vascular Endothelial Growth Factor A

Pazopanib, an oral antiangiogenic agent, is associated with improved outcomes in patients with metastatic renal cell carcinoma. In this retrospective analysis, we explore hypertension, an on-target adverse event, as a predictive marker.. Data from the pazopanib arm of the phase III COMPARZ trial (NCT00720941) comprised the test set. Pooled data from phase II (NCT00244764) and III (NCT00334282) pazopanib trials comprised the validation set. Data from the sunitinib arm of COMPARZ were analysed separately. Measures of efficacy were response rate, progression-free survival (PFS), and overall survival (OS). Mean arterial blood pressure (MAP) was the primary metric, and systolic hypertension (S-HTN) and diastolic hypertension (D-HTN) were secondary metrics; 4- and 12-week landmark analyses were performed.. Analyses revealed no significant associations at the landmarks between response and MAP. We observed a trend towards improved PFS with S-HTN at week 4 (hazard ratio [HR] = 0.79, P = 0.060) and week 12 (HR = 0.75, P = 0.073) among pazopanib-treated patients in COMPARZ. This trend was not confirmed at week 12 in the validation set or in sunitinib-treated patients. In the test set, there was a trend towards increased OS in patients with S-HTN by week 4 (HR = 0.76, P = 0.062) and with D-HTN by week 4 (HR = 0.71, P = 0.016) but not by week 12. No significant differences in OS were observed in sunitinib-treated patients for S-HTN or D-HTN.. Neither hypertension nor any blood pressure elevation above baseline was associated with efficacy outcomes of pazopanib or sunitinib. Accordingly, management of tyrosine kinase inhibitor-induced hypertension is unlikely to compromise outcome.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Blood Pressure; Carcinoma, Renal Cell; Clinical Trials as Topic; Female; Humans; Hypertension; Indazoles; Indoles; Kidney Neoplasms; Male; Middle Aged; Pyrimidines; Pyrroles; Retrospective Studies; Sulfonamides; Sunitinib; Treatment Outcome

Evaluation of the safety and efficacy of pazopanib, a multikinase angiogenesis inhibitor, in a single-arm, open-label, extension study (VEG107769/NCT00387764) for placebo-treated patients with advanced renal cell carcinoma (RCC) from a randomized, double-blind, placebo-controlled phase III study (VEG105192/NCT00334282).. Patients received pazopanib 800 mg/day. The primary endpoint was the safety and tolerability of pazopanib treatment. Secondary endpoints included response rate per Response Evaluation Criteria in Solid Tumors, progression-free survival (PFS), and overall survival (OS).. Seventy-nine placebo-treated patients from VEG105192/NCT00334282 who experienced disease progression and one pazopanib-treated patient (an exemption) were enrolled. Forty-one patients (51%) were treatment-naive; 39 (49%) were cytokine-pretreated. Median exposure to pazopanib was 9.7 months. All patients had discontinued pazopanib at the time of analysis. The most common reason for discontinuation was disease progression (61%). The most common adverse events were hypertension (45%), diarrhea (45%), hair color changes (44%), anorexia (30%), and nausea (25%). The response rate was 37.5% [95% confidence interval (CI): 26.9-48.1]; median PFS was 9.2 months (95% CI: 7.3-12.0); median OS was 23.5 months (95% CI: 16.3-28.0).. Efficacy and safety profiles for pazopanib in this extension study of patients with RCC previously treated with placebo were very similar to those observed for pazopanib-treated patients in the pivotal phase III study.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Anorexia; Carcinoma, Renal Cell; Diarrhea; Disease-Free Survival; Female; Hair Color; Humans; Hypertension; Indazoles; Kaplan-Meier Estimate; Kidney Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoplasm Staging; Pyrimidines; Randomized Controlled Trials as Topic; Severity of Illness Index; Sulfonamides; Treatment Outcome

In this randomised phase III study (VEG105192; NCT00334282), pazopanib previously demonstrated statistically and clinically meaningful improvement of progression-free survival versus placebo in patients with advanced/metastatic renal cell carcinoma (mRCC). Final overall survival (OS) and updated safety results are now reported.. Treatment-naive or cytokine-pretreated mRCC patients (n=435) stratified and randomised (2:1) to pazopanib 800 mg daily or placebo, were treated until disease progression, death or unacceptable toxicity. Upon progression, placebo patients could receive pazopanib through an open-label study. Final OS in the intent-to-treat population was analysed using a stratified log-rank test. Rank-preserving structural failure time (RPSFT) and inverse probability of censoring weighted (IPCW) analyses were performed post-hoc to adjust for crossover.. The difference in final OS between pazopanib- and placebo-treated patients was not statistically significant (22.9 versus 20.5 months, respectively; hazard ratio [HR]=0.91; 95% confidence interval [CI], 0.71-1.16; one-sided P=.224). Early and frequent crossover from placebo to pazopanib and prolonged duration of crossover treatment confounded the OS analysis. In IPCW analyses, pazopanib decreased mortality (HR=0.504; 95% CI, 0.315-0.762; two-sided P=.002). Similar, albeit non-significant, results were obtained in RPSFT analyses (HR=0.43; 95% CI, 0.215-1.388; two-sided P=.172). Since the last cutoff, cumulative exposure to pazopanib increased by 30%. The pazopanib safety profile showed no new safety signals or changes in the type, frequency and severity of adverse events.. Although no significant difference in OS was observed in this study, extensive crossover from placebo to pazopanib confounded final OS analysis. Post-hoc analyses adjusting for crossover suggest OS benefit with pazopanib treatment for mRCC patients.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Carcinoma, Renal Cell; Cross-Over Studies; Diarrhea; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension; Indazoles; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Sulfonamides; Treatment Outcome

Patients with early-stage, resectable, non-small-cell lung cancer (NSCLC) are at risk for recurrent disease, and 5-year survival rates do not exceed 75%. Angiogenesis inhibitors have shown clinical activity in patients with late-stage NSCLC, raising the possibility that targeting the vascular endothelial growth factor pathway in earlier-stage disease may be beneficial. This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC.. Patients scheduled for resection received oral pazopanib 800 mg/d for 2 to 6 weeks preoperatively. Tumor response was measured by high-resolution computed tomography, permitting estimation of change in tumor volume and diameter. Gene-expression profiling was performed on 77 pre- and post-treatment lung samples from 34 patients.. Of 35 patients enrolled, 33 (94%) had clinical stage I NSCLC and two (6%) had clinical stage II NSCLC. Median treatment duration was 16 days (range, 3 to 29 days). Thirty patients (86%) achieved tumor-volume reduction after pazopanib treatment. Two patients achieved tumor-volume reduction > or = 50%, and three patients had partial response according to Response Evaluation Criteria in Solid Tumors. Pazopanib was generally well tolerated. The most common adverse events included grade 2 hypertension, diarrhea, and fatigue. One patient developed pulmonary embolism 11 days after surgery. Several pazopanib target genes and other angiogenic factors were dysregulated post-treatment.. Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.

Topics: Administration, Oral; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Diarrhea; Drug Administration Schedule; Fatigue; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Hypertension; Indazoles; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Pyrimidines; Sulfonamides; Treatment Outcome

Pazopanib is an oral angiogenesis inhibitor of vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor, and cytokine receptor. This open-label, randomized, crossover, phase I study evaluated the effect of low- and high-fat meals on the pharmacokinetics (PK) of pazopanib in patients with advanced solid tumors. Patients participated in either the lead-in cohort or randomized food-effect cohort. Patients in the lead-in cohort were administered a single dose of pazopanib 400 mg with a high-fat meal. Patients in the food-effect cohort were randomized to receive single doses of pazopanib 800 mg in fed condition (high- or low-fat meal) or fasting condition, in random sequence 14 days apart. After completion of the study, patients were given the opportunity to continue treatment with daily pazopanib 800 mg. Administration of pazopanib with both low- and high-fat meals increased maximum observed plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC) by approximately twofold as compared with the corresponding values when administered to patients in the fasted condition. Therefore, pazopanib should be administered to patients in the fasted state so as to minimize within- and between-day variability in the systemic exposure to pazopanib in patients with cancer.

Topics: Administration, Oral; Adult; Aged; Cohort Studies; Cross-Over Studies; Dietary Fats; Fatigue; Female; Food-Drug Interactions; Humans; Hypertension; Indazoles; Male; Middle Aged; Neoplasms; Pyrimidines; Sulfonamides

The safety, pharmacokinetics, and clinical activity of pazopanib (GW786034), an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit, were evaluated in patients with advanced-stage refractory solid tumors.. Patients were enrolled into sequential dose-escalating cohorts (50 mg three times weekly to 2,000 mg once daily and 300-400 mg twice daily). Escalation or deescalation was based on toxicities observed in the preceding dose cohort. Pharmacokinetic and biomarker samples were obtained. Clinical response was assessed every 9 weeks.. Sixty-three patients were treated (dose escalation, n = 43; dose expansion, n = 20). Hypertension, diarrhea, hair depigmentation, and nausea were the most frequent drug-related adverse events, the majority of which were of grade 1/2. Hypertension was the most frequent grade 3 adverse event. Four patients experienced dose-limiting toxicities at 50 mg, 800 mg, and 2,000 mg once daily. A plateau in steady-state exposure was observed at doses of >or=800 mg once daily. The mean elimination half-life at this dose was 31.1 hours. A mean target trough concentration (C(24)) >or=15 microg/mL (34 micromol/L) was achieved at 800 mg once daily. Three patients had partial responses (two confirmed, one unconfirmed), and stable disease of >or=6 months was observed in 14 patients; clinical benefit was generally observed in patients who received doses of >or=800 mg once daily or 300 mg twice daily.. Pazopanib was generally well tolerated and showed antitumor activity across various tumor types. A monotherapy dose of 800 mg once daily was selected for phase II studies.

Topics: Administration, Oral; Adult; Aged; Angiogenesis Inhibitors; Anorexia; Cohort Studies; Diarrhea; Drug Administration Schedule; Fatigue; Female; Humans; Hypertension; Indazoles; Male; Middle Aged; Nausea; Neoplasms; Pyrimidines; Sulfonamides; Vomiting

We sought to examine cardiovascular toxicities associated with tyrosine kinase inhibitors in pediatrics. We examined 1624 pediatric adverse events with imatinib, dasatinib, sorafenib, pazopanib, crizotinib, and ruxolitinib reported to the Food and Drug Administration between January 1, 2015, and August 14, 2020. There were 102 cardiovascular event reports. Hypertension was the most commonly reported cardiovascular event and was most frequently associated with sorafenib and pazopanib. The presence of infection increased the reporting odds of cardiovascular events overall and specifically cardiac arrest, heart failure, and hypertension. These data provide early insight into cardiovascular toxicities with tyrosine kinase inhibitor use in pediatrics.

Topics: Antineoplastic Agents; Child; Heart Failure; Humans; Hypertension; Protein Kinase Inhibitors; Sorafenib; Tyrosine Kinase Inhibitors; United States; United States Food and Drug Administration

Drug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored.. A 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence.. Pazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS.

Topics: Aged; Amlodipine; Angiogenesis Inhibitors; Antihypertensive Agents; Antineoplastic Agents; Carcinoma, Renal Cell; Combined Modality Therapy; Diabetic Nephropathies; Dihydropyridines; Drug Substitution; Edema; Everolimus; Humans; Hypertension; Indazoles; Kidney Failure, Chronic; Lung Neoplasms; Male; Nephrotic Syndrome; Nivolumab; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pneumonectomy; Protein Kinase Inhibitors; Pyrimidines; Sirolimus; Sulfonamides; Sunitinib

Vandetanib and pazopanib are clinically available, multi-targeted inhibitors of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. Short-term VEGF receptor inhibition is associated with hypertension in 15%-60% of patients, which may limit the use of these anticancer therapies over the longer term. To evaluate the longer-term cardiovascular implications of treatment, we investigated the "on"-treatment (21 days) and "off"-treatment (10 days) effects following daily administration of vandetanib, pazopanib, or vehicle, in conscious rats. Cardiovascular variables were monitored in unrestrained Sprague-Dawley rats instrumented with radiotelemetric devices. In Study 1, rats were randomly assigned to receive either daily intraperitoneal injections of vehicle (volume 0.5 mL; n = 5) or vandetanib 25 mg/kg/day (volume 0.5 mL; n = 6). In Study 2, rats received either vehicle (volume 0.5 mL; n = 4) or pazopanib 30 mg/kg/day (volume 0.5 mL; n = 7), dosed once every 24 hours for 21 days. All solutions were in 2% Tween, 5% propylene glycol in 0.9% saline solution. Vandetanib caused sustained increases in mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) compared to baseline and vehicle. Vandetanib also significantly altered the circadian cycling of MAP, SBP, and DBP. Elevations in SBP were detectable 162 hours after the last dose of vandetanib. Pazopanib also caused increases in MAP, SBP, and DBP. However, compared to vandetanib, these increases were of slower onset and a smaller magnitude. These data suggest that the cardiovascular consequences of vandetanib and pazopanib treatment are sustained, even after prolonged cessation of drug treatment.

Topics: Animals; Arterial Pressure; Disease Models, Animal; Drug Administration Schedule; Humans; Hypertension; Indazoles; Male; Piperidines; Pyrimidines; Quinazolines; Random Allocation; Rats; Rats, Sprague-Dawley; Sulfonamides

Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid-suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real-world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression-free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety-one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.

Topics: Aged; Female; Humans; Hypertension; Indazoles; Male; Middle Aged; Progression-Free Survival; Proton Pump Inhibitors; Pyrimidines; Sarcoma; Sulfonamides; Treatment Outcome

In the setting of metastatic RCC (mRCC), pazopanib is approved as first line therapy. Unfortunately treatment may lead to cardiotoxicity such as hypertension, heart failure, and myocardial ischemia.. Define the in vivo role of pazopanib in the development of cardiotoxicity.. Wild type mice were dosed for 42 days via oral gavage, and separated into control and treatment (pazopanib) groups. Baseline ECG's, echocardiograms, and blood pressures were recorded. At the conclusion of the study functional parameters were again recorded, and animals were used for pathological, histological, and protein analysis.. After 2 weeks of dosing with pazopanib, the treatment group exhibited a statistically significant increase in mean arterial pressure compared to control mice (119 ± 11.7 mmHg versus 108 ± 8.2 mmHg, p = 0.049). Treatment with pazopanib led to a significant reduction in the cardiac output of mice.. Our findings in mice clearly demonstrate that treatment with pazopanib leads to a significant elevation in blood pressure after 2 weeks of dosing and this persists for the duration of dosing. The continued development of the cardio-oncology field will be paramount in providing optimal oncologic care while simultaneously improving cardiac outcomes through further investigation into the mechanisms of CV toxicity.

Topics: Angiogenesis Inhibitors; Animals; Arterial Pressure; Body Weight; Carcinoma, Renal Cell; Cardiac Output; Disease Models, Animal; Echocardiography; Electrocardiography; Heart; Hypertension; Indazoles; Kidney; Kidney Neoplasms; Mice; Myocardium; Pyrimidines; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Sulfonamides; Vascular Endothelial Growth Factor A

Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1. With a single-center prospective observational design, patients with metastatic renal cell carcinoma (n=27) treated with the receptor tyrosine kinase inhibitor pazopanib were included in the study. Home blood pressure was measured, and plasma and urine samples were collected at baseline and after 4 and 8 weeks of treatment. After 4 weeks, systolic and diastolic blood pressures increased, whereas heart rate decreased significantly; urine protein/creatinine ratio increased significantly, whereas estimated glomerular filtration rate was unchanged. Urine nitrite/nitrate (NOx) and cGMP/creatinine ratios decreased significantly, whereas urine endothelin-1/creatinine ratio and FE

Topics: Administration, Oral; Aged; Carcinoma, Renal Cell; Cohort Studies; Denmark; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glomerular Filtration Rate; Hospitals, University; Humans; Hypertension; Indazoles; Kidney Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Nitric Oxide; Prospective Studies; Pyrimidines; Risk Assessment; Sulfonamides; Time Factors

Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma.. In this open-label, multicentre, single-arm trial, adults with advanced unresectable cholangiocarcinoma received pazopanib 800 mg daily and trametinib 2 mg daily until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) with secondary end points including overall survival (OS), response rate, and disease control rate (DCR).. A total of 25 patients were enrolled and had received a median of 2 prior systemic therapies (range 1-7). Median PFS was 3.6 months (95% CI: 2.7-5.1) and the 4-month PFS was 40% (95% CI: 24.7-64.6%). There was a trend towards increased 4-month PFS as compared with the prespecified null hypothesised 4-month PFS of 25%, but this difference did not reach statistical significance (P=0.063). The median survival was 6.4 months (95% CI: 4.3-10.2). The objective response rate was 5% (95% CI: 0.13-24.9%) and the DCR was 75% (95% CI: 51%, 91%). Grade 3/4 adverse events attributable to study drugs were observed in 14 (56%) and included thrombocytopenia, abnormal liver enzymes, rash, and hypertension.. Although the combination of pazopanib plus trametinib had acceptable toxicity with evidence of clinical activity, it did not achieve a statistically significant improvement in 4-month PFS over the prespecified null hypothesised 4-month PFS.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Disease Progression; Disease-Free Survival; Drug Eruptions; Exanthema; Female; Humans; Hypertension; Indazoles; Male; MAP Kinase Kinase Kinases; Middle Aged; Protein Kinase Inhibitors; Pyridones; Pyrimidines; Pyrimidinones; Receptors, Vascular Endothelial Growth Factor; Sulfonamides; Survival Rate; Thrombocytopenia

Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs).. We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for known risk factors.. Progression-free survival (PFS) and overall survival (OS) were similar among patients with baseline HTN (n = 197; 65%) versus patients with no baseline HTN (n = 106; 35%) (PFS; P = .72) (OS; P = .54). There was a significant difference between patients with treatment-induced HTN (n = 110) versus patients with no treatment-induced HTN (n = 193) for PFS (15.6 vs. 6.4 months, respectively; P < .001) and OS (34.9 vs. 13.9 months, respectively; P < .001). Use of ASIs at baseline (n = 126; 41.6%) had no impact on outcome as compared with patients receiving other antihypertensive medication (n = 71; 23.4%) or with patients with no baseline antihypertensive medication (n = 106; 35.0%). Among patients with TKI-induced HTN (n = 110), however, ASI users (n = 91) demonstrated improved OS (37.5 vs. 18.1 months; P = .001) and PFS (17.1 vs. 7.2 months; P = .004) versus ASI nonusers (n = 19), respectively.. Our results demonstrate survival benefit for ASI users among patients with TKI-induced HTN. These results, however, require further validation in a prospective setting.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Carcinoma, Renal Cell; Female; Humans; Hypertension; Indazoles; Indoles; Kidney Neoplasms; Male; Middle Aged; Proportional Hazards Models; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Sulfonamides; Sunitinib; Treatment Outcome; Young Adult

Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large-scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real-life, postmarketing surveillance data.. Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS.. The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression-free survival for all patients was 15.4 weeks. The median progression-free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively.. There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft-tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408-16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Chemical and Drug Induced Liver Injury; Disease-Free Survival; Female; Fibrosarcoma; Humans; Hypertension; Indazoles; Japan; Leiomyosarcoma; Liposarcoma; Male; Middle Aged; Neoplasm Recurrence, Local; Neurilemmoma; Pneumothorax; Product Surveillance, Postmarketing; Pyrimidines; Retrospective Studies; Sarcoma; Sarcoma, Synovial; Sulfonamides; Survival Analysis; Thrombocytopenia

Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) are widely used for the treatment of metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the association between treatment-related hypertension and the therapeutic efficacy of VEGFR-TKIs.. Clinical data of 155 mRCC patients treated with VEGFR-TKIs at the Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were retrospectively analyzed. All patients received first-line TKI therapy. Among them, 69 patients were treated with sunitinib, 14 cases with pazopanib, and 51 cases with fazotinib. Kaplan-Meier curves were used to evaluate the survival of the patients.. The median survival for the whole group (n=155) was 36.2 months. Among the 98 (63.2%) patients who developed hypertension, 9 patients (5.8%) were evaluated as grade Ⅰ, 54 (34.8%) as grade Ⅱ and 35 (22.6%) as grade Ⅲ, and there was no patient with grade Ⅳ hypertension. The occurrence of TKI-related hypertension was correlated with age and MSKCC score (P<0.05), while not significantly correlated with gender, nephrectomy, T stage, number of metastases, lung metastasis or sunitinib treatment (P>0.05 for all). For the whole group (n=155), the therapeutic efficacy rate was 43.2% (67/155), the median progression-free survival (PFS) was 12.0 months, and the median overall survival (OS) was 36.2 months. The response rate (RR) was 26.3% (15/57) in patients with normal blood pressure and 53.1% (52/98) in patients with hypertension (P=0.001). The median PFS was 7.1 months in the cases with normal blood pressure and 13.8 months in patients with hypertension (P=0.032). The response rates were 33.3% (3/9), 51.9% (28/54) and 60.0% (21/35) in patients with grade Ⅰ, Ⅱ and Ⅲ hypertension (P=0.006). The median PFS was 7.1, 9.7, and 12.0 and 19.5 months in patients with normal blood pressure, and patients with grade Ⅰ, Ⅱ and Ⅲ hypertension, respectively (P=0.039). Both univariant and multivariant analyses indicated that treatment-related hypertension is an important predictive factor for the efficacy of VEGFR-TKIs therapy.. Hypertension might be an effective predictive factor for efficacy of VEGFR-TKIs therapy in mRCC patients. Large-sample studies are warranted to further prove these results.

Topics: Carcinoma, Renal Cell; Disease-Free Survival; Female; Humans; Hypertension; Indazoles; Indoles; Kidney Neoplasms; Male; Neoplasm Metastasis; Nephrectomy; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Sulfonamides; Sunitinib; Vascular Endothelial Growth Factor A

Reliable biomarkers of pazopanib's efficacy in soft tissue sarcoma (STS) are lacking. Hypertension (HTN) is an on-target effect of vascular endothelial growth factor (VEGF)-receptor inhibitors such as pazopanib. We evaluated the association of pazopanib-induced HTN with antitumour efficacy in patients with metastatic non-adipocytic STS.. Associations between pazopanib-induced-HTN and antitumour efficacy were retrospectively assessed across 2 prospective studies (European Organisation for Research and Treatment of Cancer (EORTC) study 62043 and 62072) in metastatic STS patients who received pazopanib 800 mg daily. Only patients with baseline blood pressure (BP)<150/90 mmHg, were included. BP was measured monthly. HTN was reported according to National Cancer Institute-Common Toxicity Criteria Adverse Events (NCI-CTC AE) grading (v3.0), and as absolute differences compared to baseline. The effect of HTN developing in patients without baseline anti-hypertensive medication was assessed on progression-free (PFS) and overall survival (OS) using a landmark analysis stratified by study; univariately using the Kaplan-Meier method and a log-rank test, and in a multivariate Cox regression model after adjustment for important prognostic factors.. Of the 337 patients eligible for this analysis, 21.7% received anti-hypertensive medication at baseline and had a similar PFS and OS compared to those who did not. In patients without baseline anti-hypertensive medication, 38.6% developed HTN. As the majority of patients developing HTN did so within 5 weeks after initiation of pazopanib (68.6%), this time point was used as landmark. Univariately, there was no effect on PFS or OS from occurrence of HTN within 5 weeks of treatment expressed either in NCI-CTC AE criteria or as maximal differences from baseline in systolic and diastolic BP. Also in multivariate analysis, after adjusting for important prognostic factors, the occurrence of HTN expressed in the different parameters was not associated with PFS and OS.. In this retrospective analysis, pazopanib-induced HTN did not correlate with outcome in pazopanib-treated STS patients. The occurrence of HTN cannot serve as biomarker in this setting.

Topics: Adult; Aged; Blood Pressure; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease-Free Survival; Europe; Female; Follow-Up Studies; Humans; Hypertension; Indazoles; Male; Middle Aged; Outcome Assessment, Health Care; Proportional Hazards Models; Prospective Studies; Protein Kinase Inhibitors; Pyrimidines; Randomized Controlled Trials as Topic; Retrospective Studies; Sarcoma; Sulfonamides

Pazopanib, a tyrosine kinase inhibitor, is one of the new registered first-line therapeutic options in the treatment of metastatic clear cell renal carcinoma. Our aim was to evaluate the efficiency and toxicity of first-line pazopanib therapy administered for patients with metastatic clear cell renal carcinoma with good- and medium prognosis according to MSKCC criteria. Between January and May, 2011, 24 patients have been treated with pazopanib in 8 oncology centers in Hungary, out of them 21 patients' data were analyzed. The mean age was 65.3 (49-81) years, 10 males and 11 females. According to MSKCC the prognosis was good and medium in 3 and 18 cases, respectively. Daily dose of pazopanib was 800 mg administered continuously in 28 day cycles. Dose reduction was performed according to the instructions of the registration study. Tumor response was evaluated according to RECIST 1.0. Currently 6 (28.6%) patients are on treatment. Dose reduction was necessary in 6 (28.6%) cases with an average duration of 14.55 (7-150) days. Mean±SE daily dose was 692.97±13.67 (400-800) mg. Median PFS was 12.41 months (95% CI 11.52-12.94 months). Complete remission (CR), as the best tumor response occurred in 2 (9.5%) cases. Partial remission (PR), stable disease (SD) and progression was observed in 6 (28.6%), 10 (47.6%) and 3 (14.3%) cases, respectively. Objective tumor response was observed in 8 pts (38%). Median survival could not be statistically analyzed yet due to the insignificant number of fatal outcomes. Median follow-up was 25.22 months (95% CI 2.47-28.1 months). As common side-effect fatigue, weakness and diarrhea occurred in 11 (52.4%), 9 (42.9%) and 8 (38%) cases, respectively. Besides these, worsening of high blood pressure and ALT/AST elevation was observed in 5 (23.8%) and 6 (28.6%) cases, respectively. Based on the initial Hungarian experiences, pazopanib is a well tolerable product and can be administered safely. According to our results its efficiency in terms of tumor response and progression-free survival is comparable to the results of the registration study.. Az áttétes világossejtes veserák egyik új, törzskönyvezett készítménye a pazopanib. Célunk az MSKCC jó és közepes prognózisú, metasztatikus világossejtes veserákos betegek elsõ vonalbeli pazopanibterápiája hatékonysági és toxicitási profiljának értékelése volt. 2011. január és május között hazánk 8 onkológiai centrumában 24 betegnél indult pazopanibkezelés, közülük 21 adatait elemeztük. Átlagéletkoruk 65,3 (49–81) év, 10 férfi, 11 nõ, MSKCC szerint 3 jó, 18 közepes prognózisú. A pazopanib dózisa 800 mg volt naponta, 28 napos ciklusokban. A tumorválasz értékelése a RECIST 1.0 szerint történt. 6 (28,6%) beteg kezelése folya matban van. Dóziscsökkentés 6 (28,6%) betegnél történt, átlagosan 14,55 (7–150) nap idõtartamban. Az átlagos napi dózis±SE 692,97±13,67 (400–800) mg. A progressziómentes túlélés medián 12,41 hónap. Komplett remisszió 2 (9,5%), részleges remisszió 6 (28,6%), stabil betegség 10 (47,6%) esetben alakult ki, 3 (14,3%) progressziót észleltünk. Objektív tumorválaszt 8 fõnél (38%) észleltünk. A medián teljes túlélés statisztikailag nem értékelhetõ a kis számú halálozási esemény miatt. A betegek követésének medián idõtartama 25,22 hónap. Leggyakoribb mellékhatások a fáradékonyság 11 (52,4%), gyengeség 9 (42,9%), hasmenés 8 (38%), magas vérnyomás kialakulása/romlása 5 (23,8%), valamint ALT/AST emelkedés 6 (28,6%). A kezdeti hazai tapasztalatok alapján a pazopanib biztonsággal alkalmazható. Hatékonysága a tumorválasz és a progressziómentes túlélés szempontjából hasonló a törzskönyvezõ vizsgálat eredményeihez.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Carcinoma, Renal Cell; Diarrhea; Disease-Free Survival; Female; Humans; Hungary; Hypertension; Indazoles; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Retrospective Studies; Sulfonamides; Treatment Outcome