Combination Therapy With Bortezomib in Renal Medullary Carcinoma: A Case Series.

Abstract Background Renal medullary carcinoma (RMC) is a very rare, aggressive neoplasm occurring almost exclusively in adolescents and young adults with sickle cell trait. Given the rare nature of this tumor, accounting for less than 0.5% of all renal carcinomas, most of the published data on therapies is from case reports and small case series, and current treatments are insufficient, with most patients succumbing to their disease in months. We report our experience with a cytotoxic chemotherapy regimen consisting of platinum-based therapy, doxorubicin, and bortezomib. Methods Three patients with metastatic RMC at a single institution were treated off-label with a perioperative chemotherapy regimen for four cycles of two alternating regimens: regimen A consisting of cisplatin, doxorubicin, and bortezomib; regimen B consisting of carboplatin, paclitaxel, and gemcitabine. A radical nephrectomy was performed on all patients. Surveillance imaging was performed on all patients to assess response and disease burden. Patients received up to 12 months of maintenance therapy with everolimus. Results Three African American patients - two males and one female aged 14, 28, and 31 – with sickle cell trait and metastatic disease were treated with this regimen. The median follow-up was 18 months. All had resection of the primary tumor – two patients after receiving neoadjuvant therapy, and one patient underwent resection prior to referral. All three patients achieved complete responses based on imaging, two of which lasted for 12 months, and another is still in remission over seven years after diagnosis. Conclusions This regimen of alternating cycles of platinum-based chemotherapy with bortezomib appeared to be active against RMC and was generally well-tolerated. Given the extremely rare nature of this disease and dismal prognosis, new treatment modalities should be pursued, and whenever possible, patients should be enrolled in a clinical trial. We propose that a multi-institution clinical trial of this regiment may be warranted.