Sequential Targeted Therapy Following Pazopanib (PZ) in Patients (PTS) with Metastatic Renal Cell Cancer (MRCC): Efficacy and Toxicity
Francisco ValladaresToni K. ChoueiriThomas E. HutsonT.B. PowlesCamillo PortaSergio BracardaMegan E. LampronLinda CerboneCora N. SternbergJoaquim Bellmunt
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Abstract Purpose Pazopanib is known to cause liver toxicity. A relationship between pazopanib exposure and alanine transaminase elevations has been described in clinical trials. This study investigated the relation between pazopanib exposure and liver toxicity in real-world patients and evaluated the management of pazopanib-induced liver toxicity in routine care. Methods A retrospective observational cohort study was performed in patients treated with pazopanib in whom pazopanib exposure was measured. The percentage of patients with and without liver toxicity during treatment with pazopanib was calculated as well as the average pazopanib exposure in both groups. Furthermore, the management of patients with liver toxicity was evaluated. Results Liver toxicity was observed in 25 out of the 133 patients included (19%). Pazopanib exposure was comparable in patients with or without liver toxicity (27.7 mg/L versus 28.1 mg/L). Seven patients permanently discontinued pazopanib after the occurrence of liver toxicity. Of the remaining 18 patients, continuation or restart of pazopanib after liver toxicity was successful in 16 patients and half of these patients were able to safely continue pazopanib at the same dose as prior to liver toxicity for the remaining duration of treatment. Conclusion Our study did not demonstrate a clear relationship between pazopanib exposure and the occurrence of pazopanib-induced liver toxicity. Half of the patients were able to safely continue or restart pazopanib treatment after liver toxicity and received the same dose as prior to drug withdrawal. Successful interventions to address pazopanib-induced toxicity in the clinic led to an algorithm for the management of pazopanib-induced liver toxicity.
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Pazopanib is a potent multi-kinase inhibitor that hinders angiogenesis and blocks tumor growth. It has been approved for the treatment of metastatic renal cell carcinoma (mRCC) and advanced soft tissue sarcoma. There is emerging evidence that bleeding is a common adverse effect of pazopanib and other targeted therapies in patients with mRCC. In addition, jaw osteonecrosis related to pazopanib was recently described in the literature. We report three cases of patients with mRCC who developed adverse oral events related to pazopanib. The first patient, treated with pazopanib as monotherapy, presented with gingival bleeding and oral burning sensation. The other two patients receiving pazopanib as monotherapy and pazopanib followed by sunitinib, respectively, presented complaining about mandibular pain; a diagnosis of medication-related osteonecrosis of the jaw (MRONJ) was rendered in both cases. Gingival bleeding and MRONJ may develop as oral side effects of pazopanib use. The cases presented here aim to alert and inform health care professionals about the risk of adverse oral events in patients with mRCC receiving the antiangiogenic agent pazopanib.
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Targeted therapy has become the mainstay in the treatment of renal cell carcinoma (RCC). That being said, it is difficult to predict which patients will respond to targeted therapy. A recent article published in The Lancet Oncology attempts to identify biomarkers in patients receiving pazopanib that may be helpful in the clinical management of renal cell carcinoma.
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Tyrosine kinase inhibitor (TKI) and its side effects are well known. However, these are mainly descriptive, with pictorial data lacking. Here, in we report a case of metastatic renal cell carcinoma, treated with TKI, with classic side effects; supplemented with images that demonstrate the adverse effects of the drug. In addition, we discuss and demonstrate the computed tomography changes.
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ì ì¥ì íììì VEGFR-TKIsê³¼ ê´ë ¨ë ì¬ë¶ì ì ë무ë ìëª ì ìíí ì ìë ìíí ë¶ìì©ì¼ë¡ pazopanibì¼ë¡ ì¸í ì¬ê°í ì¬ë¶ì ì ê±°ì ìë ê²ì¼ë¡ ìë ¤ì ¸ ìë¤. êµë´ìì pazopanibì¼ë¡ ì¸í ì¬ê°í ì¬ë¶ì ì ëíì¬ìë ë³´ê³ ë ë°ê° ìë¤. ì´ì ì ìë¤ì pazopanib í¬ì¬í ì´í ë°ìí ì¬ê°í ì¬ë¶ì 1ì를 ê²½ííìì¼ë©° pazopanib í¬ì¬ì 주기ì ì¸ ì¬ì¥ê¸°ë¥ íê° íìì± ë° ì¦ì ë°í ìì ì½ë¬¼ ì¤ë¨ì íµíì¬ ì¦ì í¸ì ì 기ëí ì ìì´ ì´ì ëíì¬ ì¦ë¡ë³´ê³ íë¤. ì¤ì¬ ë¨ì´: íì¡°íë; ì ì¥ì; ì¬ë¶ì
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Tyrosine kinase inhibitors sunitinib and pazopanib are used as first-line agents in the treatment of metastatic renal cell carcinoma. Treatment-related toxicities have been described with both these drugs. This report describes a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is, to the best of our knowledge, the first such case to be reported.
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Background/ Aim: We evaluated surgical outcomes following nephrectomy and thrombectomy with and without presurgical treatment with pazopanib in patients with advanced renal cell carcinoma with inferior vena caval tumor thrombosis. Materials and Methods: We compared surgical outcomes between patients undergoing presurgical treatment with pazopanib vs. surgery-alone in 19 patients who underwent surgery for advanced renal cell carcinoma with high-level inferior vena caval tumor thrombosis at the Kobe University Hospital. Results: Comparing the presurgical group with the surgery-alone group, respectively, the average operative time was 497 min vs. 627 min (p=0.08); average blood loss was 1,928 ml vs. 7,393 ml (p<0.05); average postoperative hospitalization duration was 15.3 days vs. 21.6 days (p=0.05); and the perioperative complication rate was lower (presurgical: 33% vs. surgery-alone: 50%). Conclusion: Presurgical treatment with pazopanib decreased surgical difficulty and improved surgical outcomes for advanced renal cell carcinoma with high-level inferior vena caval tumor thrombosis.
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Renal cell carcinoma is the most common type of kidney cancer in adults. It accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. At the moment several biological agents are used for the treatment of metastatic renal cell carcinoma. We describe the case of a man who has been treated with pazopanib (Votrient) for metastatic renal cell carcinoma since July 2011. At the time of writing, the patient is still receiving treatment (29 months) and is showing a long-lasting response with a favorable safety profile. This is an excellent example of chronic neoplastic disease in a patient who can be defined as long-surviving.
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Renal cell carcinoma is one of the leading causes of cancer worldwide. Brain metastasis is a poor prognostic factor among patients with this disease. The advancements in understanding of the molecular framework behind malignancy and brain metastasis led to more sophisticated treatment regimens which include targeted drugs and immunotherapy. While the role of tyrosine kinase inhibitors in metastatic renal cell carcinoma has been proven in the literature, its specific role among patients with brain metastasis has not yet been fully elucidated. We report a case of a Filipino male with renal cell carcinoma and brain metastasis who underwent stereotactic radiosurgery of his right frontal lesion followed by pazopanib taken initially at 800 mg/day and then decreased to 600 mg/day. A significant increase in creatinine level led to the discontinuation of the medication after >3 years. He had a remarkable progression-free survival of 38 months. This is the first documented case of such significant response to pazopanib in a patient with renal cell carcinoma and brain metastasis. In the Philippine setting where options for cancer treatment are limited by the prohibitive cost of medications, this case can support the use of pazopanib as a potent agent for treating patients with this condition.
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Renal cell carcinoma is the most common type of kidney cancer in adults. It accounts for approximately 3% of adult malignancies and 90–95% of neoplasms arising from the kidney. At the moment several biological agents are used for the treatment of metastatic renal cell carcinoma. We describe the case of a man who has been treated with pazopanib (Votrient) for metastatic renal cell carcinoma since July 2011. At the time of writing, the patient is still receiving treatment (29 months) and is showing a long-lasting response with a favorable safety profile. This is an excellent example of chronic neoplastic disease in a patient who can be defined as long-surviving.
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