C. Cianci

Radium 223 dichloride: a multidisciplinary approach to metastatic castration-resistant prostate cancer

The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were β-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor types.

Safety and antitumor efficacy of 153Sm-EDTMP and docetaxel administered sequentially to patients with metastatic castration-resistant prostate cancer

BackgroundBone metastases are responsible for most of the morbidity associated with metastatic castration-resistant prostate cancer (mCRPC). Bone-seeking radiopharmaceuticals have been approved for palliation of painful skeletal metastases, but their clinical use is limited by concerns of toxicities both when administered alone and especially when combined with chemotherapy agents. ObjectiveWe investigated whether docetaxel administered to mCRPC patients after treatment with samarium-153-labeled ethylene-diamine-tetra-methylene-phosphonic acid (153Sm-EDTMP) has increased toxicity and/or reduced antitumor efficacy. Materials and methodsThirty mCRPC patients with skeletal metastases were enrolled. Patients received standard therapy with docetaxel (75 mg/m2 intravenously every 21 days for at least six cycles) on average 6 weeks after 153Sm-EDTMP (37 MBq/kg). Patients were monitored for the presence of toxicities, and antitumor efficacy was assessed by changes in serum prostate-specific antigen levels. Besides standard descriptive statistical analysis, progression-free survival and overall survival were defined using the Kaplan–Meier method. ResultsOver 80% of the patients showed favorable biochemical responses. Median time to progression was 9.1 months (mean 9.8, 95% confidence interval 7.8–9.9), and median overall survival was 19.9 months (mean 24.5, 95% confidence interval 16.9–22.8); five patients were still alive over 5 years after enrollment. No additional hematological toxicities were observed when docetaxel was administered after 153Sm-EDTMP other than those expected when administering the agent alone. ConclusionPrior administration of 153Sm-EDTMP does not cause additional toxicities for subsequent treatment with docetaxel and does not reduce the antitumor efficacy of the latter. This work justifies further investigations on the possible synergistic effects of combined strategies with the two agents.

Alpha‐2B‐interferon plus floxuridine in metastatic renal cell carcinoma a phase I‐II study

Background. Both alpha‐interferon and floxuridine are active in metastatic renal cell carcinoma (MRCC); the two agents have demonstrated antitumor synergism and different clinical toxicities. The purpose of this study was to determine the maximum tolerable dose (MTD) of floxuridine (FUDR), administered as a constant continuous infusion for 14 days every 28 days, in combination with fixed doses of alpha‐2B‐interferon and to preliminarily evaluate the antitumor activity of this combination.

223Ra-chloride therapy in men with hormone-refractory prostate cancer and skeletal metastases: Real-world experience

Background: Radium-223 (223Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223Ra therapy in routine clinical practice. Methods: A total of 83 patients with metastatic CRPC were treated with 223Ra at 3 Italian centers between August 2013 and August 2016. 223Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response. Results: Patients had a median age of 75 (range 53–89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved (p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of 223Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. 223Ra was well-tolerated. Conclusions: 223Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.