Motexafin gadolinium for the treatment of metastatic renal cell carcinoma: phase II study results.
BACKGROUND
Thioredoxin reductase (Trx) has been implicated in activation of hypoxia-inducible factor-1alpha, which is overexpressed in > 85% of renal cell carcinomas (RCCs). We evaluated the safety and efficacy of motexafin gadolinium (MGd), a Trx inhibitor, as a single-agent therapy for metastatic RCC.


METHODS
Patients with metastatic RCC were infused daily with MGd 5 mg/kg on days 1-5 and days 15-19 of each 28-day cycle. Patients were evaluated for response on days 21-28 of every third cycle. Those with tumor response or stable disease (SD) continued treatment for < or = 12 cycles. Twenty-five patients with confirmed metastatic RCC were enrolled. All were evaluable for toxicity, and 20 were evaluable for response.


RESULTS
While no clinical responses were observed, 8 patients had SD after 3 treatment cycles, as did 4 after 6 cycles. Median overall survival was 10.1 months, and median progression- free survival was 2.7 months. The most common treatment-related toxicities were grade 1/2 pain, nausea, skin discoloration, fatigue, blisters, and headache. The most common grade 3 toxicity was hypophosphatemia, observed in 5 patients. MGd was reasonably tolerated, and disease stabilization was observed in several patients with metastatic RCC.


CONCLUSIONS
These results show promise for the use of MGd in combination with other molecularly targeted therapies in previously treated patients with metastatic RCC. However, further investigation of MGd alone for metastatic RCC is not recommended.
Amato
Robert J
RJ
Department of Internal Medicine, Division of Oncology, The University of Texas Health Science Center, Memorial Hermann Hospital, Houston, TX 77030, USA. ramato@uth.tmc.edu
Jac
Jaroslaw
J
Hernandez-McClain
Joan
J
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis
D008665:Metalloporphyrins; C437683:motexafin gadolinium