Cedric Lebacle1, Karim Bensalah2, Jean-Christophe Bernhard3,4, Laurence Albiges5, Brigitte Laguerre6, Marine Gross-Goupil7, Herve Baumert8, Herve Lang9, Thibault Tricard9, Brigitte Duclos10, Armelle Arnoux11, Celine Piedvache11, Jean-Jacques Patard12, Bernard Escudier5. 1. Department of Urology, Bicetre University Hospital, Assistance Publique-Hôpitaux de Paris, APHP, University Paris-Saclay, Le Kremlin-Bicetre, France. 2. Department of Urology, Pontchaillou University Hospital, Rennes, France. 3. Department of Urology, Bordeaux University Hospital, Pellegrin Hospital, Bordeaux, France. 4. French Research Network on Kidney Cancer UroCCR, Bordeaux, France. 5. Department of Medicine, Gustave Roussy, University Paris-Saclay, Villejuif, France. 6. Department of Oncology, Eugene Marquis Centre, Rennes, France. 7. Department of Medical Oncology, Bordeaux University Hospital, Saint-Andre Hospital, Bordeaux, France. 8. Department of Urology, Saint-Joseph Hospital, Paris, France. 9. Department of Urology, Nouvel Hopital Civil, Strasbourg University Hospital, Strasbourg, France. 10. Department of Oncology, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France. 11. Paris-Sud Clinical Research Unit, Department of Statistics, Bicetre University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France. 12. Department of Urology, Mont de Marsan Hospital, Mont de Marsan, France.
Abstract
OBJECTIVE: To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function. PATIENTS AND METHODS: Patients with cT2aN0NxM0 clear-cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7-10 mg, was administered twice daily, for 2-6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib. RESULTS: Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5 (70-98) mm and 11 (7-11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III-V post-surgery complications. At 2-year follow-up, six patients had metastatic progression, and two had a recurrence. CONCLUSION: Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.
OBJECTIVE: To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function. PATIENTS AND METHODS: Patients with cT2aN0NxM0 clear-cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7-10 mg, was administered twice daily, for 2-6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib. RESULTS: Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5 (70-98) mm and 11 (7-11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III-V post-surgery complications. At 2-year follow-up, six patients had metastatic progression, and two had a recurrence. CONCLUSION: Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.
Authors: Sebastien J Hotte; Anil Kapoor; Naveen S Basappa; Georg Bjarnason; Christina Canil; Henry J Conter; Piotr Czaykowski; Jeffrey Graham; Samantha Gray; Daniel Y C Heng; Pierre I Karakiewicz; Christian Kollmannsberger; Aly-Khan A Lalani; Scott A North; François Patenaude; Denis Soulières; Phillippe Violette; Eric Winquist; Lori A Wood; Shaan Dudani; Ranjena Maloni; M Neil Reaume Journal: Can Urol Assoc J Date: 2019-10 Impact factor: 1.862
Authors: Nirmish Singla; Roy Elias; Rashed A Ghandour; Yuval Freifeld; Isaac A Bowman; Leonid Rapoport; Mikhail Enikeev; Jay Lohrey; Solomon L Woldu; Jeffrey C Gahan; Aditya Bagrodia; James Brugarolas; Hans J Hammers; Vitaly Margulis Journal: Urol Oncol Date: 2019-09-12 Impact factor: 2.954