Phase 2 Study of Lutetium 177–Labeled Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma

Muselaers, Stijn; Boers‐Sonderen, Marye J.; Oostenbrugge, Tim J. van; Boerman, Otto C.; Desar, Ingrid M.E.; Stillebroer, Alexander B.; Mulder, Sasja F.; Herpen, Carla M.L. van; Langenhuijsen, Johan F.; Oosterwijk, Egbert; Oyen, Wim J.G.; Mulders, Peter F.A.

doi:10.1016/j.eururo.2015.11.033

Cited by 59 publications

(57 citation statements)

References 10 publications

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“…CAIX mAbs have been developed that allow delivery of radioisotopes and cytotoxic drugs to cancer cells [205,206]. A phase II trial of 177 Lu-girentuximab in metastatic clear cell renal carcinoma attained stable disease in 9 of 14 patients [207]. Another inhibitor indisulam, which demonstrated promising preclinical activity [208], has undergone phase II clinical trials for stage IV melanoma, renal clear cell carcinoma and metastatic breast cancer [209], although in advanced NSCLC patients there was little response when it was used as second-line therapy [210].…”

Section: Carbonic Anhydrase IXmentioning

confidence: 99%

The impact of tumour pH on cancer progression: strategies for clinical intervention

Ward

Meehan

Gray

et al. 2020

Exploration of Targeted Anti-Tumor Therapy

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Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H+-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets.

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Section: Carbonic Anhydrase IXmentioning

confidence: 99%

The impact of tumour pH on cancer progression: strategies for clinical intervention

Ward

Meehan

Gray

et al. 2020

Exploration of Targeted Anti-Tumor Therapy

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“…After Stillbroer et al [ 57 ] determined the maximum tolerated dose of 177Lu-girentuximab in a phase I study, Muselaers et al [ 58 ] evaluated in 2015, in a phase II non-randomized single-arm trial, the efficacy of 177 Lu-girentuximab. Fourteen metastatic ccRCC patients with evidence of progressive disease were enrolled between April 2011 and August 2014.…”

Section: Evidence Synthesismentioning

confidence: 99%

Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management

Courcier

Taille

Nourieh

et al. 2020

IJMS

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Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes. Renal carcinoma encompasses a broad spectrum of histological entities and is also described as a heterogeneous malignant tumor. Recently, various combinations of checkpoint inhibitors and targeted therapies have been validated to manage this disease. Reliable markers to confirm the diagnosis, estimate the prognosis, predict or monitor the treatment response are required. Molecular imaging developments allow a comprehensive analysis of the tumor, overcoming the spatial heterogeneity issue. CAIX, being highly expressed at the tumor cell surfaces of clear cell renal carcinoma, also represents a potential treatment target. In this manuscript we reviewed the current knowledge from the literature on the pathophysiological interactions between renal cell carcinoma and CAIX, the role of CAIX as a marker for diagnosis, prognosis, treatment monitoring and molecular imaging, and the potential target for therapeutic strategies.

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“…In the phase II clinical trial, stable disease was experienced by 57% of the patients with manageable toxicity, especially low blood cell counts [103]. A randomized, double-blind, placebocontrolled phase III clinical trial evaluated girentuximab as an adjuvant therapy in 864 patients with high risk of postoperative recurrence RCC [104].…”

Section: Immunotherapymentioning

confidence: 99%

Systemic treatment of renal cell cancer: A comprehensive review

Sánchez-Gastaldo

Kempf

Alba

et al. 2017

Cancer Treatment Reviews

130

102

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Kidney cancer represents about 5% of all new cancer diagnoses. The most common form of kidney cancer arises from renal epithelium, named renal cell carcinoma (RCC). This entity comprises different histological and molecular subtypes. Unraveling the molecular biology and cytogenetic of RCC has enabled the development of several targeted agents that have improved treatment outcomes of these patients. This article reviews all the agents currently approved for the treatment of RCC, and discuss upcoming molecules. Mechanism of action, preclinical and clinical development and ongoing trials, are presented for each agent, providing a broad vision of the current state of targeted therapy in RCC and possible future developments.

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Phase 2 Study of Lutetium 177–Labeled Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma

Cited by 59 publications

References 10 publications

The impact of tumour pH on cancer progression: strategies for clinical intervention

The impact of tumour pH on cancer progression: strategies for clinical intervention

Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management

Systemic treatment of renal cell cancer: A comprehensive review

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