Sorafenib and sunitinib cause hypothyroidism in a subset of patients. This retrospective study examined the incidence of hypothyroidism and its relationship to progression-free survival in renal cell carcinoma. We found that hypothyroidism occurs more frequently in patients treated with sunitinib and correlates with a longer progression-free survival, which could be useful as a biomarker for response to therapy. Introduction Sunitinib and sorafenib are tyrosine kinase inhibitors used in metastatic renal cell carcinoma and are known to cause hypothyroidism in a subset of patients. The goal of this study was to better characterize the development of hypothyroidism in patients and to examine its relationship to progression-free survival. Patients and Methods A retrospective chart review was performed on patients treated with sunitinib or sorafenib from January 1, 2005, to January 1, 2011. Data pertaining to the treatment course and development of hypothyroidism were extracted. Patients with hypothyroidism at the beginning of treatment were analyzed separately. Results A total of 73 treatment periods had sufficient data to analyze. Among patients with normal baseline thyroid function, 15 (44%) of 34 patients treated with sunitinib and 6 (27%) of 22 patients treated with sorafenib developed hypothyroidism. The hazard ratio for the development of hypothyroidism with sorafenib vs. sunitinib treatment was significant, at 0.38 (95% CI, 0.14–0.97). There was a statistically significant difference in the progression-free survival between patients who developed hypothyroidism while receiving treatment compared with those who did not, 18.2 vs. 10.1 months (P = .01). Conclusions This study demonstrated a significant difference in the incidence of hypothyroidism during treatment with sunitinib and sorafenib, with a higher incidence of hypothyroidism in patients treated with sunitinib. The development of hypothyroidism was associated with a longer progression-free survival.

Objectives The purpose of this study was to assess the efficacy and safety of low-dose (1mg) daily diethylstilbestrol (DES) for the treatment of castrate-resistant prostate cancer (CRPC). Methods and Materials A retrospective chart review was performed on patients treated with low-dose DES who had CRPC despite anti-androgen withdrawal. The study population consists of 63 patients treated in the pre- and post-chemotherapy settings based on a database review; 58 had sufficient data for efficacy, all were analyzed for safety. Results A PSA decrease of ≥50% was observed in 19 of 49 pre-chemotherapy patients (39%) with a median time to progression (TTP) of 30 weeks (95% CI, 21.9, 68.7). A PSA decrease of <50% was seen in another 16 patients (33%) with a median TTP of 16.4 weeks (95% CI, 13.0, 37.6). Fourteen patients (29%) had progressive disease by PSA testing; their median TTP was 6.9 weeks (95% CI, 5.6, 12.9). Thromboembolic events included 2 patients with DVTs and 1 patient who developed primary fibrinolysis syndrome. Additional adverse events included gynecomastia in 37 of 63 patients (59%). Secondary observations include PSA responses in 3 of 9 patients treated with DES after chemotherapy progression and a high rate of PSA responses in patients retreated with DES after a drug holiday. Conclusions Low-dose DES is safe and effective in a modern cohort of men with CRPC despite anti-androgen treatment. Its potential role in the post-chemotherapy setting and the suggestion of efficacy on re-challenge merits additional consideration.

Increases in the mean corpuscular volume (MCV) have been observed in patients with metastatic renal cell carcinoma (mRCC) on tyrosine kinase inhibitor (TKI) treatment; however, its association with progression‐free‐survival (PFS) is unknown. We aimed to characterize TKI‐associated macrocytosis in mRCC and its relationship with PFS. Retrospective review of data on macrocytosis and thyroid dysfunction on mRCC patients treated with sunitinib and/or sorafenib. These results are evaluated in the context of our previous report on the association of hypothyroidism in this setting. We assessed PFS as clinically defined by the treating physician. Seventy‐four patients, 29 of whom received both drugs, were included. A treatment period was defined as time from initiation to discontinuation of either sunitinib or sorafenib; 103 treatment periods [sorafenib (47), sunitinib (56)] were analyzed. Macrocytosis was found in 55 and 8% of sunitinib‐ and sorafenib‐treated patients, respectively, P < 0.001. The median time to developing macrocytosis was 3 months (m, range 1–7). Median PFS in sunitinib‐treated patients was 11 m (95% CI: 6–19). Median PFS was higher among those with macrocytosis compared to normocytosis (21 m [95% CI: 11–25] vs. 4 m [95% CI: 3–8] P = 0.0001). Macrocytosis and hypothyroidism were two significant predictors of PFS. The greatest difference in PFS among all patients was observed in patients with both macrocytosis and hypothyroidism (25 m), compared to the normocytic and euthyroid patients (5 m) (P < 0.0001). Sunitinib‐related macrocytosis was associated with prolonged PFS, and concurrent development of hypothyroidism and macrocytosis further prolonged PFS. Increased MCV may have a role as a predictive biomarker for sunitinib. Prospective studies accounting for other known prognostic factors are needed to confirm this finding.

453 Background: Increases in mean corpuscular volume (MCV) and hypothyroidism have been observed in patients on sunitinib treatment. We characterized tyrosine kinase-associated macrocytosis in metastatic renal cell carcinoma (mRCC) patients and its relationship, along with thyroid dysfunction, to progression-free survival (PFS). Methods: A retrospective chart review was performed on patients treated with sunitinib and/or sorafenib (01/2005-01/2011). Data pertaining to the development of macrocytosis was analyzed in association with our previous data on thyroid dysfunction in these patients. We assessed PFS, as clinically defined by the treating provider. Results: Seventy-four patients with 103 treatment periods for sorafenib (47) and sunitinib (56) were analyzed. Macrocytosis was found in 55% and 8% of sunitinib and sorafenib treatment periods, respectively (p<0.001). Focusing on the sunitinib-treated patients for all further analysis, the median PFS was 11 months (mo) (95% CI, 6-19). Median PFS was 21 mo (95% CI, 11-25) for patients who developed macrocytosis compared to 4 mo (95% CI, 3-8) in normocytic patients (p=0.0001). The time to development of macrocytosis did not affect the degree of macrocytosis observed (p=0.47). Macrocytosis and hypothyroidism were both significant predictors of prolonged PFS in our cohort. The greatest difference in PFS was noted between patients who developed both macrocytosis and hypothyroidism (25 mo) versus those who remained both normocytic and euthyroid (5 mo) (p<0.0001). Conclusions: Sunitinib-related macrocytosis is associated with a prolonged PFS in mRCC. The concurrent development of both hypothyroidism and macrocytosis in this setting was associated longer PFS compared to either alone. Increased MCV may be used as a biomarker for sunitinib response in this setting. [Table: see text]