Factors influencing survival and toxicity of Ra223 (Xofigo) treatment

Objectives We evaluated several factors including pre-existing hematotoxicity (HT) with regard to their impact on survival, hematotoxicity and number of Xofigo treatments.

Methods In 56 patients with metastatic CRPC that underwent Xofigo therapy data on hemoglobin-levels (Hb), number of platelets (Plts) and leukocytes (Leuk) before, during and after therapy were collected. The extent of bone metastases, chemotherapies applied was assessed, too. Pre-therapeutic HT as well as adverse events (AE) were scored (grade 0-4) according to the CTCAE recommendations. These factors were analyzed with regard to development of severe HT (grade 3/4 hemoglobin, platelet and leukocyte counts) during therapy, the number of Xofigo treatments, and survival.

Results Overall survival of included patients was 69.9 weeks. Patients with pre-existing HT of grade 2 had significantly shorter survival (20 weeks vs not reached, P<0,001), fewer treatment cycles (5.1 vs 5.8, P<0.04), and developed significantly more grade 3 and 4 HT (0 vs 26.7%, P<0,001). This effect was even more pronounced in patients demonstrating grade 1 thrombocytopenia (21 weeks vs not reached; P<0,001, grade 3/4 HT 14.6 vs 62.5%; P=0.002; cycles 5.6 versus 3.4; P<0.001) Neither extent of bone metastases, nor previous chemotherapy had influence on survival, number of Xofigo cycles and hematotoxicity.

Conclusions Higher grades of HT before Xofigo therapy were significantly related to survival and the development of severe HT during therapy, mainly affecting hemoglobin values, thus leading to increasing numbers of premature termination of Xofigo treatments.