pazopanib and Hand-Foot-Syndrome

Pazopanib is a novel multikinase inhibitor that shares a similar spectrum of target receptors with sorafenib and sunitinib. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib and compare the difference in incidence between sorafenib, sunitinib, and pazopanib. Relevant studies were identified from PubMed (1998-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. A total of 1,163 patients from 10 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 4.5% (95% CI: 2.5-7.9%) and 1.8% (95% CI: 0.7-4.6%), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased for all-grade (RR = 6.09, 95% CI: 1.11-33.36, p = 0.037) and high-grade HFSR (RR = 2.51, 95% CI: 0.12-51.9, p = 0.55). The risk of all-grade and high-grade HFSR to pazopanib was significantly lower as compared to sorafenib and sunitinib (RR = 7.5, 95% CI: 5.5-10.2, p < 0.001; RR = 5.9, 95% CI: 3.5-10.0, p < 0.001 and RR = 4.2, 95% CI: 3.0-5.7, p < 0.001; RR = 3.6, 95% CI: 2.1-6.2, p < 0.001). Despite sharing the same spectrum of target receptors with sorafenib and sunitinib, pazopanib is associated with an unexpectedly low risk of HFSR. Further investigations are needed to elucidate HFSR pathogenesis.

Topics: Hand-Foot Syndrome; Humans; Incidence; Indazoles; Protein Kinase Inhibitors; Pyrimidines; Risk Factors; Skin; Sulfonamides

Hand-foot syndrome and mucositis/stomatitis are frequent adverse events (AEs) of treatment with tyrosine kinase inhibitors in cancer therapy. Quality-of-life instruments that measure the functional consequences of these AEs are needed to assess the impact of therapeutic interventions and to guide patient care. The Hand-Foot and Mucositis Symptom and Impact Questionnaire (HAMSIQ [formerly the Supplementary Quality of Life Questionnaire]) was used in the COMPARZ trial (Pazopanib vs Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma [national clinical trial no. NCT00720941]) and the PISCES study (Patient Preference Study of Pazopanib vs Sunitinib in Advanced or Metastatic Kidney Cancer [clinicaltrials.gov NCT01064310]) to assess mouth/throat and hand/foot soreness symptoms and subsequent limitations in patients receiving pazopanib or sunitinib for metastatic renal cell carcinoma. The objective of the current analysis was to validate the HAMSIQ using data from the PISCES study.. The HAMSIQ was administered in the PISCES study at baseline and every 2 weeks over two 10-week periods to patients who were receiving pazopanib or sunitinib. Data from the first 10-week period were used to assess the feasibility, validity, and responsiveness of the HAMSIQ.. In total, ≥85% of 169 patients completed the HAMSIQ (excluding the item concerning days off work). Correlations among items within the same limitation subscale generally were high (Cronbach α ≥ .80). HAMSIQ limitation scores differentiated patients according to their baseline performance status and severity of soreness. Small-to-moderate correlations were observed for the symptoms/limitation scores and for changes from baseline scores between the HAMSIQ and the Functional Assessment of Chronic Illness Therapy fatigue survey. The HAMSIQ demonstrated responsiveness to changes in clinical status and the development of hand-foot syndrome AEs over time.. The HAMSIQ is a feasible, valid, reliable, and responsive instrument for assessing the impact of hand-foot syndrome and mucositis in patients receiving tyrosine kinase inhibitors. Cancer 2016;122:287-295. © 2015 American Cancer Society.

Topics: Adult; Aged; Carcinoma, Renal Cell; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Hand-Foot Syndrome; Humans; Indazoles; Indoles; Kidney Neoplasms; Lymph Nodes; Male; Maximum Tolerated Dose; Middle Aged; Mucositis; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Pyrimidines; Pyrroles; Quality of Life; Risk Assessment; Sulfonamides; Sunitinib; Surveys and Questionnaires; Treatment Outcome

Pazopanib is a multitargeted tyrosine kinase inhibitor used as a standard treatment for chemotherapy-refractory recurrent or metastatic soft tissue sarcoma. This study aimed to evaluate the efficacy and safety of pazopanib for treatment of metastatic soft tissue sarcoma in the Asian population.. Fifty patients with chemotherapy-refractory recurrent or metastatic soft tissue sarcoma, who had received pazopanib treatment between 2015 and 2016 were enrolled. We reviewed patients' clinical characteristics and studied survival outcomes following pazopanib treatment.. Median follow-up was 5.7 months. Seven patients were still on pazopanib by the end of this study and the disease had progressed in the other 43 patients, leading to 23 deaths. We found that despite treatment more than half the patients experienced disease progression (56% vs 14% partial response and 30% stable disease). The median progression-free survival and overall survival was 3.1 and 11.0 months, respectively. Multivariate analysis identified good Eastern Cooperative Oncology Group performance status (0 or 1) and occurrence of hand-foot skin reaction as independent factors associated with better outcome. Hand-foot skin reaction was 32% in our cohort and the median onset time was 4 (1.00-8.29) weeks. It had dose-dependent effect by clinical observation.. Our study showed that the incidence rate of hand-foot skin reaction in Taiwan is higher than western population, and it is an independent predictive factor for better treatment outcomes.

Topics: Adult; Aged; Asian People; Disease Progression; Disease-Free Survival; Female; Hand-Foot Syndrome; Humans; Indazoles; Male; Middle Aged; Predictive Value of Tests; Protein Kinase Inhibitors; Pyrimidines; Retrospective Studies; Sarcoma; Sulfonamides; Taiwan; Treatment Outcome

Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies.. The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks.. Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m(2) , a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD.. In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Axitinib; Bevacizumab; Carcinoma, Renal Cell; Databases, Factual; Diarrhea; Drug Administration Schedule; Fatigue; Female; Hand-Foot Syndrome; Humans; Imidazoles; Indazoles; Indoles; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Middle Aged; Models, Statistical; Molecular Targeted Therapy; Mucositis; Niacinamide; Phenylurea Compounds; Predictive Value of Tests; Pyrimidines; Pyrroles; Retrospective Studies; Risk Assessment; Risk Factors; Sorafenib; Sulfonamides; Sunitinib; Vascular Endothelial Growth Factor A

Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.

Topics: Aged; Angiogenesis Inhibitors; Hand-Foot Syndrome; Humans; Indazoles; Male; Pulmonary Artery; Pyrimidines; Sulfonamides; Tunica Intima; Vascular Neoplasms