Renal Cell Cancer Presented with Leptomeningeal Carcinomatosis Effectively Treated with Sorafenib

Ranze, Oliver; Hofmann, Erich; Distelrath, Andrea; Hoeffkes, Heinz-Gert

doi:10.1159/000105131

Cited by 21 publications

(12 citation statements)

References 3 publications

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“…Interactions of sorafenib with P-gp or ABCG2 are thus far not reported. However, a few case reports indicated that sorafenib can achieve partial remission in renal cell carcinoma patients with brain metastases (8,9). Although brain metastases may contain leaky blood vessels due to neovascularization, they are often protected from adequate chemotherapy because they are still mostly behind an intact blood-brain barrier (BBB; reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

Breast Cancer Resistance Protein and P-glycoprotein Limit Sorafenib Brain Accumulation

Lagas

Waterschoot

Sparidans

et al. 2010

Molecular Cancer Therapeutics

165

123

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Sorafenib is a second-generation, orally active multikinase inhibitor that is approved for the treatment of patients with advanced renal cell carcinoma and patients with unresectable hepatocellular carcinoma. We studied active transport of sorafenib in MDCK-II cells expressing human P-glycoprotein (P-gp/ABCB1) or ABCG2 (breast cancer resistance protein) or murine Abcg2. Sorafenib was moderately transported by P-gp and more efficiently by ABCG2 and Abcg2. Because sorafenib is taken orally, we orally administered sorafenib to wild-type, Abcb1a/1b −/− , Abcg2 −/− , and Abcb1a/1b;Abcg2 −/− mice, completely lacking functional Abcb1a/1b, Abcg2, or both, respectively, and we studied plasma pharmacokinetics and brain accumulation. The systemic exposure on oral administration was not different among all strains. However, brain accumulation was 4.3-fold increased in Abcg2 −/− mice and 9.3-fold increased in Abcb1a/1b;Abcg2 −/− mice. Moreover, when wildtype mice were treated with sorafenib in combination with the dual P-gp and ABCG2 inhibitor elacridar, brain accumulation was similar to that observed for Abcb1a/1b;Abcg2 −/− mice. These results show that the brain accumulation of sorafenib is primarily restricted by ABCG2. This contrasts with previous studies using shared ABCG2 and P-gp substrates, which all suggested that P-gp dominates at the blood-brain barrier, and that an effect of ABCG2 is only evident when both transporters are absent. Interestingly, for sorafenib, it is the other way around, that is, ABCG2, and not P-gp, plays the dominant role in restricting its brain accumulation. Clinically, our findings may be relevant for the treatment of renal cell carcinoma patients with central nervous system relapses, as a dual ABCG2 and P-gp inhibitor might improve the central nervous system entry and thereby the therapeutic efficacy of sorafenib. Mol Cancer Ther; 9(2); 319-26. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

Breast Cancer Resistance Protein and P-glycoprotein Limit Sorafenib Brain Accumulation

Lagas

Waterschoot

Sparidans

et al. 2010

Molecular Cancer Therapeutics

165

123

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“…NM from renal cell carcinoma is a rare event, with only few cases reported to date [2,3]. In the present patient, it was preceded by brain metastases, initially a single cerebellar lesion, which was surgically removed.…”

Section: Discussionmentioning

confidence: 63%

“…Some patients might even present with leptomeningeal carcinomatosis or so called neoplastic meningitis (NM). Only few cases of NM from renal cell carcinoma treated with contemporary systemic approaches have been reported [2,3]. Therefore, the present case illustrates important aspects around potential treatment options.…”

Section: Introductionmentioning

confidence: 83%

Leptomeningeal carcinomatosis from renal cell cancer: treatment attempt with radiation and sunitinib (case report)

2010

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A case of leptomeningeal carcinomatosis in a patient with known brain and lung metastases from renal cell cancer without previous systemic therapy is presented. Neoplastic meningitis (NM) developed 31 months after first diagnosis of simultaneous extra- and intracranial recurrence of kidney cancer and surgical resection of a cerebellar metastasis. In spite of local radiotherapy to the macroscopic NM lesions in the cervical and lumbar spine followed by initiation of sunitinib, the patient succumbed to his disease 4 months after the diagnosis of NM. The untreated lung metastases progressed very slowly during almost 3 years of observation. This case illustrates important issues around both biological behaviour and treatment approaches in metastatic renal cell cancer.

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“…Por otra parte, recientemente están apareciendo en la literatura casos de regresiones rápidas de focos metastáticos en el sistema nervioso central tras la administración de sunitinib y sorafenib 39,40 .…”

Section: Metástasis Cerebralesunclassified

Tratamiento quirúrgico de las metástasis del cáncer renal

Ruiz-Cerdá

Cruz

2009

Actas Urol Esp

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E l cáncer renal (CR) representa el 2% de todos los cánceres 1 . En Europa, se diagnostican cada año 40.000 pacientes con CR de los cuales fallecen aproximadamente la mitad 2 . Un tercio de los pacientes presentan un estadio localmente avanzado o diseminado en el momento del diagnóstico 3 . Además, un 25% de los pacientes portadores de enfermedad localizada intervenidos con intención curativa desarrollan progresión en forma de recidiva local o a distancia 4 .Se considera que un paciente es portador de CR con diseminación limitada (CRDL) cuando, en el momento del diagnóstico (sincrónica) o durante el seguimiento (metacrónica), presenta un sólo foco metastático o varios en un mismo órgano, siempre y cuando sean técnica, funcional y oncológicamente resecables. Si bien, cada día se está siendo más agresivo quirúrgicamente. Incluso en casos de metástasis múltiples 5 . La incidencia de metástasis en un sólo órgano (uno o múltiples focos) oscila entre 2,5-3,2% 6 . En estudios autópsicos varia entre el 8-11% 7 . Aunque la evolución es muy variable, se estima que el 35-40 % de los pacientes consiguen sobrevivir 5 años 8 . En ocasiones, la metástasis se diagnostica antes que el CR originario tras el informe anatomopatológico de un tumor considerado inicialmente primitivo del órgano donde asienta. Lo más frecuente es que se descubra de forma sincró-nica con el diagnóstico del tumor primitivo renal, o bien, durante el seguimiento post-nefrectomía. Esta circunstancia tiene importancia pronóstica porque, se ha demostrado que las tasas de supervivencia a ResumenLa extirpación completa de lesiones metastásicas pueden contribuir a mejorar el pronóstico clínico del cáncer renal. Hoy en día, se acepta que la extirpación quirúrgica de las metástasis solitarias para los pacientes con cáncer renal es la única posibilidad de supervivencia a largo plazo. Siempre que las metástasis puedan ser técnica y funcionalmente resecadas. Esta revisión se refiere a la evidencia actual sobre metástasis resecables del cáncer renal a nivel de pulmón, hígado, hueso, riñón y otros órganos.Los criterios para considerar a un paciente como candidato a la resección de metástasis son: control de tumor primario, extirpación quirúrgica de viabilidad y la falta de enfermedad sistémica. En pacientes con metástasis sincrónicas, la extirpación quirúrgica debe realizarse al mismo tiempo que la nefrectomía. El pronóstico clínico es peor cuando las metás-tasis son asíncronas. Tras la introducción de las nuevos agentes anti-angiogénicos, también se justifica la cirugía en pacientes con buena respuesta. Si bien, este enfoque sigue estando en el ámbito de la investigación.Palabras clave: Cancer renal. Metastasis. Tratamiento quirúrgico. Surgical treatment for renal cancer metastases AbstractComplete removal of metastatic lesions can contribute to improve clinical prognosis of renal cáncer. Nowadays, it is accepted that surgical extirpation of solitary metastases for patients with renal cancer is the only potential for long-term survival. Provided that the metastases c...

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Renal Cell Cancer Presented with Leptomeningeal Carcinomatosis Effectively Treated with Sorafenib

Cited by 21 publications

References 3 publications

Breast Cancer Resistance Protein and P-glycoprotein Limit Sorafenib Brain Accumulation

Breast Cancer Resistance Protein and P-glycoprotein Limit Sorafenib Brain Accumulation

Leptomeningeal carcinomatosis from renal cell cancer: treatment attempt with radiation and sunitinib (case report)

Tratamiento quirúrgico de las metástasis del cáncer renal

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