pazopanib and Kidney-Failure--Chronic

Sporadic data are available about pazopanib use in patients with metastatic renal cell carcinoma (mRCC) undergoing dialysis and no systematic review has been previously performed about this issue.. The objective of the present mini-review is to provide an overview of clinical outcomes of pazopanib in this population, in order to support the clinical oncologist for the treatment choice and management.. All the literature ever published about mRCC dialysis patients receiving pazopanib, until August 2015, was evaluated: only two case series emerged from our search and one more patient from our department was also included, with a total of 11 mRCC dialysis patients overall. Moreover, we described our case of intrapatient dose titration of pazopanib during dialysis.. The continued treatment schedule, the short half-life, the predominantly hepatic metabolism, the wide possibility of dose modulation, the favorable tolerability profile and the similar efficacy respect to sunitinib represent factors in favor of pazopanib as first line mRCC treatment in dialysis patients. The knowledge and the good management of toxicity during pazopanib treatment can lead, also in dialysis patients, to the best and longest application of the drug, taking into account the concept of a dose escalation guided by toxicity as a marker of efficacy. The review, together with our single case report, confirmed the efficacy, the good tolerability and the maneuverability of pazopanib treatment in mRCC patients undergoing dialysis.

Topics: Adult; Angiogenesis Inhibitors; Carcinoma, Renal Cell; Dose-Response Relationship, Drug; Half-Life; Humans; Indazoles; Kidney Failure, Chronic; Kidney Neoplasms; Male; Pyrimidines; Renal Dialysis; Sulfonamides; Treatment Outcome

Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.. We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases.. This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.

Topics: Acetates; Aged, 80 and over; Calcium Compounds; Carcinoma, Renal Cell; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Humans; Indazoles; Kidney Failure, Chronic; Kidney Neoplasms; Male; Oxalates; Pancreatic Neoplasms; Pancrelipase; Protein Kinase Inhibitors; Pyrimidines; Renal Dialysis; Sulfonamides; Treatment Outcome

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

Limited data are available regarding patients with renal cell carcinoma and ESRD treated with TTs. The objective of this study was to explore the tolerability and safety of TT in patients with mRCC and ESRD.. We retrospectively identified patients with mRCC and ESRD treated at the University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Patient characteristics including demographic, histology, treatment, and adverse events are reported. Duration of treatment (TOT) was determined from date of drug initiation to discontinuation. Overall survival (OS) was determined from initiation of TT to death. Statistics are descriptive.. Fourteen patients were identified. Ten patients had clear-cell histology and 4 had papillary histology. The median number of TTs per patient was 3 (range, 1-4) with median TOT of 28 months for all TTs. Eighty-eight percent of all toxicities were Grade 1 to 2; no Grade 4 toxicities were noted. Treatment discontinuations included 3 patients treated with sorafenib due to hand-foot syndrome, intolerable fatigue, and squamous cell skin cancer development; 2 patients treated with pazopanib due to intolerable fatigue and increased transaminase levels; and 1 patient treated with everolimus due to pneumonitis. Eight patients died from progressive disease. Median OS from initiation of TT was 28.5 months and 35 months from time of diagnosis.. Toxicities were mild to moderate and consistent with those reported in previous studies. TTs appear to be safe, well tolerated and produce antitumor response in patients with mRCC and ESRD receiving dialysis.

Topics: Aged; Antineoplastic Agents; Carcinoma, Renal Cell; Disease-Free Survival; Everolimus; Female; Humans; Indazoles; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Pyrimidines; Renal Dialysis; Retrospective Studies; Sirolimus; Sorafenib; Sulfonamides; Treatment Outcome