A Phase II Trial of Gefitinib (Iressa, ZD1839) in Stage IV and Recurrent Renal Cell Carcinoma

Dawson, Nancy A.; Guo, Chuanfo; Zak, Richard D.; Dorsey, Brenda; Smoot, J.; Wong, Jade; Hussain, Arif

doi:10.1158/1078-0432.ccr-04-0310

Cited by 101 publications

(40 citation statements)

References 39 publications

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“…Could Kallio et al clarify/rectify whether the prominent membranous EGFRvIII immunostaining in that study was associated with a good prognosis in patients with RCC? While no clear association has been found between the expression of the EGFR and response to the EGFR inhibitors in cancer patients, including patients with RCC, the expression of membranous EGFR and/or EGFRvIII in RCC patients would, however, make them an ideal target for therapy with the anti-EGFR antibodies (Modjtahedi et al, 2003;Dawson et al, 2004;Rowinsky et al, 2004;Dancey, 2004). We would appreciate clarification from Kallio et al …”

Section: Sirmentioning

confidence: 92%

Is membranous location of EGFR or EGFRvIII immunostaining associated with good prognosis in renal cell carcinoma?

Modjtahedi

Cunningham

2005

Br J Cancer

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Section: Sirmentioning

confidence: 92%

Is membranous location of EGFR or EGFRvIII immunostaining associated with good prognosis in renal cell carcinoma?

Modjtahedi

Cunningham

2005

Br J Cancer

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“…One possibility, among several, is that resistance in this setting reflects the activation of alternative angiogenic pathways. Inhibitors of epidermal growth factor receptor (EGFR), which is the receptor for TGF-a, have so far been disappointing in the clinic, 80 …”

Section: 58mentioning

confidence: 99%

Treatment of kidney cancer

Kaelin

2009

Cancer

105

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Germline inactivation of the VHL tumor suppressor gene is associated with an increased risk of clear cell carcinoma of the kidney in the context of von Hippel-Lindau (VHL) disease. Somatic VHL mutations are also common in nonhereditary (sporadic) clear cell carcinomas. The VHL protein (pVHL) has multiple functions that might be linked to tumor suppression, including targeting the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. HIF, especially HIF2a, appears to play a causal role in clear cell renal carcinogenesis based on genotype-phenotype correlations in VHL disease, laboratory experiments with human VHLÀ/À renal carcinoma cell lines, and genetically engineered mouse models. Deregulation of HIF almost certainly accounts for the high levels of vascular endothelial growth factor (VEGF) observed in kidney cancer and relates to their sensitivity to VEGF inhibitors. In addition, the beneficial effects of mammalian target of rapamycin (mTOR) inhibitors are likely due to, at least partly, their ability to down-regulate HIF. pVHL, in a HIF-independent manner, also regulates a specialized structure called the primary cilium and regulates apoptosis via factors such as NFjB. Loss of the primary cilium probably facilitates the development of preneoplastic renal cysts, whereas increased NFjB might contribute to the resistance of kidney cancers to conventional cytotoxic agents. Last year more than 12,000 people died of kidney cancer in the United States.1 Clear cell carcinoma is the most common histologic form of kidney cancer and accounts for most kidney cancer deaths. Individuals who bear a defective VHL tumor suppressor gene allele in their germline (von Hippel-Lindau [VHL] disease) are at increased risk for clear cell carcinoma of the kidney and other tumors, including vascular tumors (hemangioblastomas) of the retina, cerebellum, and spinal cord and adrenal gland tumors (pheochromocytomas).2 The development of disease in this setting is linked to spontaneous inactivation or loss of the remaining wild-type VHL allele. Biallellic VHL inactivation due to somatic mutations can also be documented in approximately 50% of sporadic clear cell carcinomas. 3 Some clear cell carcinomas that retain a wild-type VHL allele fail to produce the VHL protein (pVHL) because the VHL gene is

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“…Los inhibidores especí-ficos de EGFR gefinitib y erlotinib son activos en el tratamiento del cáncer de pulmón, aunque en cáncer renal su actividad es menor. En los estudios fase II con gefitinib en cáncer renal se han observado respuestas entre el 0 y el 5% de los pacientes [62][63][64] , si bien la tasa de estabilizaciones fue mayor del 40% y la tolerancia fue muy buena. No obstante, este fármaco no se está desarrollando más en cáncer renal.…”

Section: Inhibidores De Egfrunclassified

Nuevos tratamientos para el carcinoma renal

Pérez-Gracia

López-Picazo

Olier

et al. 2007

Anales Sis San Navarra

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RESUMENEl cáncer renal presenta varias características que lo diferencian de otros tumores. El aumento de supervivencia observado en pacientes con carcinoma renal metastásico tras la realización de nefrectomía, rompe un concepto clásico de la oncología según el cual la extirpación del tumor primario en tumores avanzados carece de sentido. Junto con el melanoma, es el único tumor en el que tratamientos inmunomoduladores, como interleukina-2 producen un beneficio clínico al paciente. El tratamiento del cáncer renal metastásico con interleukina-2 intravenosa a dosis altas ha confirmado en estudios aleatorios que puede producir respuestas completas de muy larga duración, en la práctica equivalentes a la curación. Por último, el cáncer renal está siendo empleado como modelo clínico para demostrar la eficacia de múl-tiples tratamientos dirigidos frente a nuevas dianas. En la actualidad se están estudiando más de 30 nuevos fárma-cos como tratamiento del cáncer renal, habiendo sido el primer tumor en el que se ha demostrado el beneficio clí-nico del tratamiento con inhibidores de la angiogénesis. En este artículo se revisan los aspectos más relevantes sobre el cáncer renal, incluyendo epidemiología, factores pronósticos, presentación clínica; bases moleculares y el estado actual de desarrollo de varios de los múltiples fár-macos que se están estudiando en esta enfermedad.Palabras clave. Cáncer renal. Interleukina-2. Interferón. Antiangiogénesis. Sunitinib. Sorafenib. Tensirolimus. ABSTRACTRenal cell carcinoma presents several unique features, which distinguish it from other tumours. The increase in survival that has been described in patients with renal cell carcinoma following nephrectomy breaks a classical rule of oncology, which states that surgery of the primary tumour has no role in the treatment of patients with advanced disease. Together with melanoma, it is the only tumour in which immunomodulatory treatments with drugs such as interleukin-2 produces a clinical benefit to patients. In randomized trials treatment of metastatic renal cell carcinoma with high dose interleukin-2 has confirmed its ability to induce long-term complete responses, which in practice can be considered equivalent to cure. Lastly, renal cell carcinoma is being used as a clinical model to demonstrate the role of several targeted treatments, with over 30 novel agents under development. It has been the first tumour type in which treatment with angiogenesis inhibitors has shown a clinical benefit. This article reviews the most relevant aspects of renal cell carcinoma, including epidemiology, prognostic factors, clinical presentation, molecular bases and the current status of development of the most relevant novel treatments for this disease.

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A Phase II Trial of Gefitinib (Iressa, ZD1839) in Stage IV and Recurrent Renal Cell Carcinoma

Cited by 101 publications

References 39 publications

Is membranous location of EGFR or EGFRvIII immunostaining associated with good prognosis in renal cell carcinoma?

Is membranous location of EGFR or EGFRvIII immunostaining associated with good prognosis in renal cell carcinoma?

Treatment of kidney cancer

Nuevos tratamientos para el carcinoma renal

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