title: Sunitinib re-challenge in metastatic renal cell carcinoma treated sequentially with tyrosine kinase inhibitors and everolimus.
abstract: Therapy of patients with metastatic renal cell carcinoma (mRCC) requires sequential use of several agents with different mechanisms and minimal cross-resistance between the different agents. Tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors prolong progression-free survival (PFS) in patients with mRCC. Re-challenge with TKIs provides clinical benefit after everolimus in patients with mRCC. We report the case of an mRCC patient with lung and bone metastases, treated sequentially with sunitinib, sorafenib and everolimus. The patient had an objective response in reducing bone metastases, but adaptative and concomitant progression in lung metastases during sunitinib re-challenge. Previously, these lung metastases had responded to sunitinib. This intriguing paradox suggests that not only was sunitinib able to target a specific metastatic site during the re-challenge, as seen by the reduction of bone metastases, but it also elicited a more invasive adaptation and progression of lung tumor cells.
authors.affiliation: AP-HP, Groupe Henri Mondor-Albert Chenevier, Oncology Service, Creteil, France. bepaule@wanadoo.fr
authors.forename: Bernard
authors.initials: B
authors.lastname: Paule
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brion
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D011859:Radiography; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000068338:Everolimus; D000077210:Sunitinib; D020123:Sirolimus