Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal cell carcinoma

Wedekind, Mary Frances; Ranalli, Mark; Shah, Nilay

doi:10.1002/pbc.26586

Cited by 14 publications

(13 citation statements)

References 17 publications

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“…Selle et al reported the use of immunotherapy in four patients where one patient with ccRCC showed a complete response . More recently, Wedekin et al reported two patients with pRCC who responded to cabozantinib . Malouf et al reported eight cases of pediatric/young adult tRCC (ages 2–28 years, average 17.4 years), only four of which had measurable disease.…”

Section: Discussionmentioning

confidence: 99%

“…1,6 In review of the literature, 20 pRCC cases were identified where RCC-directed medical treatment is detailed with some outcome data included, the majority being individual case reports and small institutional reports . [24][25][26][27][28][29][30][31][32] Many of the reported pRCC cases include the administration of preoperative chemotherapy on the suspicion that the tumor was a Wilms tumor rather than pRCC. 33 Indolfi et al list immunotherapy as primary treatment for nine pRCC patients; however, no data are presented to demonstrate the effect of such therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Wedekin et al reported two patients with pRCC who responded to cabozantinib. 24 . 31 An additional report of serial antiangiogenic therapies demonstrated disease survival surpassing 5 years.…”

Section: Ttp Range (Days)mentioning

confidence: 99%

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Treatment of advanced pediatric renal cell carcinoma

Ambalavanan

Geller

2019

Pediatric Blood & Cancer

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Background Pediatric renal cell carcinoma (pRCC) is the second most common renal malignancy of childhood; however, treatment data for advanced disease is lacking. Methods A retrospective analysis of pRCC patients (age < 21 years at diagnosis) treated between 2000 and 2015 at Cincinnati Children's Hospital Medical Center was undertaken, with specific focus on medical therapies, accompanied by a detailed literature review. Results Twenty‐four patients (median age = 15 years) were identified; 11 were female. Past history of kidney pathology (4) and prior hematologic/oncologic diagnoses (5) were common associated findings. Translocation morphology RCC (tRCC) was the most common subtype (16; 64%), followed by papillary (6; 24%), clear cell renal cell carcinoma (ccRCC) (1), and chromophobe (1). The TNM stage distribution was I (8; 33%), II (2; 8%), III (3; 13%), and IV (11; 46%). Eleven patients with stage IV disease all had tRCC and received medicinal anticancer therapies, the most common being antiangiogenic (10), conventional chemotherapy (8), mTOR inhibition (7), and immunotherapy (3). Four patients also received small‐port radiotherapy. The mean time to progression (TTP) was longest for axitinib (n = 2; TTP = 7.8 m; range 5.5‐10 m) and sunitinib (n = 6; TTP = 4.7 m; range 0.3–12 m). Overall, 20 cases of pediatric RCC who received RCC‐directed medicinal therapy with outcome data have been previously reported. Conclusions For patients with unresectable pRCC requiring systemic therapy, available data are scarce. Data herein support an increased TTP with antiangiogenic therapy in tRCC supporting a formal study of antiangiogenic therapies through multicooperative‐group collaboration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Treatment of advanced pediatric renal cell carcinoma

Ambalavanan

Geller

2019

Pediatric Blood & Cancer

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“…The development of imatinib, an inhibitor of the BCR-ABL fusion tyrosine kinase, revolutionized the treatment of chronic myelogenous leukemia [218] and other leukemias expressing this fusion protein [219] . While these kinase inhibitors are generally designed for specificity for one kinase, often times they have effects on multiple kinases due to homology among the proteins, with varying toxicity and efficacy [220][221][222][223] . With these drugs, resistance often develops with time as well.…”

Section: New Therapies New Mechanisms Of Resistancementioning

confidence: 99%

Dodging the bullet: therapeutic resistance mechanisms in pediatric cancers

Shah¹

2019

CDR

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While advances in the treatment of pediatric cancers have improved survival to > 80% across all tumor types, drug resistance continues to limit survival for a considerable number of patients. We review the known mechanisms of resistance in pediatric cancers, including processes that impair conventional chemotherapies, newer classes of targeted small molecule antineoplastic drugs, and monoclonal antibodies. We highlight similarities and differences in treatment approach and resistance between pediatric and adult cancers. We also discuss newer areas of research into drug resistance, including extracellular and immune factors.

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“…Unfortunately, there are little to no treatments available for patients who are diagnosed with unresectable metastatic renal cell tumors, since radiation and chemotherapy are ineffective in this setting (De Pasquale et al, ; Ramphal, Pappo, Zielenska, Grant, & Ngan, ). Recent studies have begun to explore the efficacy of molecularly targeted therapies, and a recent report demonstrated that pediatric patients with TFE3 translocation renal cell tumors demonstrate improvement after treatment with the tyrosine kinase inhibitor, cabozantinib (Wedekind, Ranalli, & Shah, ). Interestingly, a recent clinical trial has shown that patients diagnosed with adulthood papillary RCC demonstrate response to cabozantinib (Campbell et al, ; Chanzá et al, ).…”

Section: Renal Cell Tumors: Most Common Renal Malignancies In Adultsmentioning

confidence: 99%

Lessons learned from the developmental origins of childhood renal cancer

Chong

Cain

2019

The Anatomical Record

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Despite the rarity of renal tumors in children, many different types of malignant and nonmalignant renal neoplasms have been described. Therefore, the correct diagnosis and clinical management of these patients can represent a challenge. Here we provide a comprehensive review of the commonly diagnosed pediatric renal malignancies, including nephroblastoma (commonly known as Wilms tumor), clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, several subtypes of renal cell tumors (often collectively termed renal cell carcinoma), and congenital mesoblastic nephroma. The epidemiology, pathology, treatments, underlying genetic and molecular mechanisms, and proposed developmental origins are discussed in detail, highlighting differential features and potential improved therapeutic strategies for affected individuals.

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Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal cell carcinoma

Cited by 14 publications

References 17 publications

Treatment of advanced pediatric renal cell carcinoma

Treatment of advanced pediatric renal cell carcinoma

Dodging the bullet: therapeutic resistance mechanisms in pediatric cancers

Lessons learned from the developmental origins of childhood renal cancer

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