Metastatic Castration-refractory Prostate Cancer Research Articles

A phase II trial of docetaxel and samarium in patients with bone metastases from castration-refractory prostate cancer (CRPC)

5122 Background: Most patients (pts) with disseminated CRPC have bone metastases. Docetaxel is the current standard of care in CRPC. We assessed the association of docetaxel and samarium, a radio-pharmaceutical with a high affinity to bone, as consolidation treatment after docetaxel-estramustine. Methods: This is a prospective, bi-center phase II trial. Pts with bone metastases from CRPC received docetaxel 70 mg/m2 day 2 + estramustine 10 mg/Kg/day, day 1–5 (1 cycle/ 3 weeks). Pts with a response or stabilization after 4 cycles were given consolidation therapy: docetaxel 20 mg/m2/week × 6 weeks + samarium 37 MBq/Kg during week 1. Zoledronic acid was routinely used and was stopped 1 month before samarium infusion. A Simon design was used with a target of 39 pts receiving consolidation treatment. Response was defined according to the working group criteria (Bubley, J Clin Oncol 1999). The primary endpoint was progression-free survival (PFS). Results: From 01/04 to 12/05, 43 pts were included in the trial: 31 (72%), 11 (26%) and 1 (3%) achieved a PSA response, stabilization, and progression, respectively. After induction therapy, a pain response (defined as a decrease in pain intensity by at least 2/10 on a pain visual analog scale (VAS) in pts with a baseline pain level = 2/10) was achieved in 60% (18/30) and was confirmed in 69% (20/29) after consolidation therapy. Consolidation docetaxel-samarium was feasible with most pts experiencing a mild (grade 1–2) and rapidly reversible thrombocytopenia at week 5. The 7 months PSA-PFS rate was 48% (33–62%). While PSA relapse eventually occurred in all cases, this strategy resulted in an excellent long-term control of pain, with a median pain level on the VAS of 4/10, 1/10, and 0.5/10 at baseline, 12, and 18 months, respectively. With a median follow-up of 14 months, the median survival has not been reached and the 1-year survival rate is 71% (55–84%). Conclusions: Combining docetaxel and samarium is feasible and well-tolerated. It yields a major pain improvement that lasts long after consolidation therapy in pts with bone metastases from CRPC. Survival data are promising in this population of symptomatic metastatic CRPC. This approach should be tested in phase III trials. No significant financial relationships to disclose.

Surgery of the Heart

Theranostics, a modern approach combining therapeutics and diagnostics, is among the most promising concepts in nuclear medicine for optimizing and individualizing treatments for many cancer entities. Theranostics has been used in clinical routines in nuclear medicine for more than 60 y—as ¹³¹I for diagnostic and therapeutic purposes in thyroid diseases. In this minireview, we provide a survey of the use of 2 different radioiodine isotopes for targeting the sodium–iodine symporter in thyroid cancer and nonthyroidal neoplasms as well as a brief summary of theranostics for neuroendocrine neoplasms and metastatic castration-refractory prostate cancer. In particular, we discuss the role of ¹²⁴I-based dosimetry in targeting of the sodium–iodine symporter and describe the clinical application of ¹²⁴I dosimetry in a patient who had radioiodine-refractory thyroid cancer and who underwent a redifferentiation treatment with the mitogen-activated extracellular signal–related kinase kinase inhibitor trametinib.