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

Borsò, Elisa; Boni, Giuseppe; Pastina, Ilaria; Lorenzoni, Alice; Cianci, C.; Federici, Francesca; Mazzarri, Sara; Orlandini, Cinzia; Francesca, F.; Selli, Cesare; Ricci, Sergio; Rubello, Domenico; Mariani, Giuliano

doi:10.1097/mnm.0000000000000023

Cited by 10 publications

(7 citation statements)

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“…Similarly, retrospective studies undertaken by a multidisciplinary team at our institution showed a possible synergistic effect on survival of Sm 153 EDTMP in combination with chemotherapy [16]. A subsequent Phase II study confirmed that the administration of docetaxel (75 mg/m 2 administered intravenously every 21 day for at least 6 cycles) after Sm 153 EDTMP (37 MBq/kg) did not induce additional toxicities and did not reduce the antitumor efficacy [17].…”

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confidence: 53%

“…Our experience with docetaxel in combination with agents that are notoriously more myelotoxic than Ra 223 suggests that this combined approach is feasible [17]. As proof, the first data from a Phase I study showed that the combination of Ra 223 (fivefold dose of 50 kBq/kg every 6 weeks) with docetaxel (60 g/m 2 every 3 weeks) appeared to be very well tolerated [25], and the next step in evaluating the efficacy is ongoing [27].…”

Section: Future Perspectivementioning

confidence: 96%

“…SAMDOCET was a randomized and multicentric study of Sm 153 EDTMP and docetaxel compared with docetaxel alone in taxane-naive patients with mCRPC [18]. The study evaluated the time to progression and overall survival of the combination of docetaxel (75 mg/m 2 for 9 cycles) and Sm 153 EDTMP (37 MBq/kg at cycles 1, 5, and 9) compared with the control arm of docetaxel alone, and the preliminary results reported a trend in survival for the combination arm.…”

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confidence: 99%

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

et al. 2014

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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. KeywordsThe management of most prostate cancer cases involves committed specialists such as urologists, medical oncologists, radiotherapists, and nuclear medicine physicians. Evidence shows that in men with high-risk prostate cancer, only a patient-focused program based on a multidisciplinary approach can result in improved survival [1]. The role of nuclear medicine physicians in this multidisciplinary team so far has been restricted to providing pain relief. In castration-resistant prostate cancer (CRPC) patients with bone metastases (mCRPC), radiopharmaceuticals turned out to be useful only for noncurative purposes, exclusively aiming at improving symptomatic pain control. In addition, the available drugs have induced considerable serious adverse events, mostly hematologic, and thus have prevented subsequent therapeutic approaches [2]. Therefore, radionuclide-based therapy for symptomatic bone metastases has remained underused and limited to the late phases of the disease [3].The lack of safe therapeutic approaches to extend survival in CRPC patients has been a challenge for nuclear medicine physicians accustomed to successfully treating other tumor types, such as thyroid tumors with radioiodine therapy, or treating hematologic malignancies with ibritumomab tiuxetan. The recent introduction of the radiopharmaceutical radium Ra 223 (Ra 223) dichloride represents a breakthrough because, for the first time, an impact of a radiopharmaceutical on survival of patients with bone metastases due to prostate cancer was demonstrated in a large Phase III trial [4]. This drug, in fact, received the category 1 recommendation as first-line and second-line option by National Comprehensive Cancer Network (NCCN) guideline similarly to chemotherapy [5], and thus the nuclear medicine physician assumed a key position in the current multidisciplinary team for the treatment of mCRPC. The team should evaluate which patients are suitable for Ra 223 dichloride without limiting access to patients in the terminal stages of the disease and should integrate the nuclear medicine physician into the team with the medical oncologist and surgeon. Future Oncol. (Epub ahead of print)

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confidence: 96%

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confidence: 99%

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

et al. 2014

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“…The nadir of platelet and white cell reductions was between 3 to 6 weeks after injection, with complete recovery by week 8-9 (15-18), less delayed and shorter in duration than with 89 Sr. There is no evidence regarding samarium improving OS when used as a single agent but this was hypothesized when 153 Sm is used sequentially or combined with docetaxel (19)(20)(21) or immunotherapy (22).…”

Section: Abstract 223 Ra Prolongs Overall Survival In Symptomatic Pamentioning

confidence: 99%

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Buroni

Persico

Pasi

et al. 2016

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Abstract. 223 Prostate cancer (PCa) is the most common malignancy in men (1). In patients affected by advanced PCa, defined as hormonesensitive disease since the tumor still requires androgen for growth, androgen deprivation therapy (ADT), including luteinizing hormone-releasing hormone (LHRH) agonists, antagonists and anti-androgens, represents the first-line treatment. Unfortunately some cancer cells develop resistance to ADT, indicating the progression of the disease to metastatic castration-resistant prostate cancer (mCRPCa). Such resistance to castration occurs in most patients (2) and, despite the approval of new therapeutic agents, mCRPCa remains a lethal disease (3). Nowadays the new therapeutic landscape for patients affected by mCRPCa aims to extend overall survival (OS) and includes cytotoxic, new-generation anti-androgens, immunotherapeutics and radiopharmaceuticals (4, 5).Bones are the preferred site of metastasis. Almost 90% of men who die from PCa have bone-metastatic disease (6), with a 5-year OS rate of 20%. Due to the fragility of bone with metastases, with the related risk of pain, fractures, spinal cord compression and hematological consequences, several drugs have been developed to treat the osseous involvement of this disease. In previous years, the optimal treatment aimed to relieve pain and reduce skeletal morbidity.Besides systemic therapies, bone-targeted agents that focus their activity on bone, such as bisphosphonates, monoclonal antibody and radiopharmaceuticals, have become available. The bisphosphonate zoledronic acid, the antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) denosumab and radiopharmaceuticals [such as 89 Sr and 153 Sm-ethylene diamine tetramethylene phosphonate ( 153 Sm-EDTMP)], were approved for delaying skeletal-related events (SREs) and for the palliation of bone pain from mCRPCa. Radionuclide TherapyRadionuclide therapy is known to deliver ionizing radiation to tumor sites, thereby killing cancer cells (7). Bone-targeted radiopharmaceuticals localize their radiation to sites of high bone remodeling. 5719

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“…Vertebral column, ribs, pelvis and the skull are among the most common sites of involvement (4). Palliative measures include, alleviation of pain, avoiding adverse effects by lowering medication dose such as corticosteroids and opioids, and preservation of patient activity and functionality (2,5). Bone seeking radiopharmaceuticals which have a strong affinity for blastic foci of bone metastases have shown favorable results in addressing such instances of bone pain.…”

Section: Introductionmentioning

confidence: 99%

153Sm-EDTMP and 177Lu-EDTMP are equally safe and effective in pain palliation from skeletal metastases

Taheri¹,

Azizmohammadi²,

Ansari³

et al. 2018

Nuklearmedizin

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Summary Introduction: Bone pain from multifocal blastic or mixed lytic-blastic metastatic lesions can be effectively addressed with radiopharmaceuticals with high affinity for such foci. 153Sm-ethylene diamine tetramethylene phosphonic acid (153Sm-EDTMP) and 177Lu-ethylene diamine tetramethylene phosphonic acid) (177Lu-EDTMP) are two such radiopharmaceuticals. The aim of this study was to make a comparison of efficacy between 153Sm-EDTMP and 177Lu-EDTMP in terms of palliation of commonly encountered symptoms in cancer patients, functional status, and pain intensity as measured by Edmonton Symptom Assessment System (ESAS), Eastern Cooperative Oncology Group (ECOG) performance status, and numeric rating scale (NRS) respectively. This study was a double blind randomized clinical trial conducted in a setting of three university hospitals. Materials and Methods: In a randomized double-blind clinical trial 50 patients will with documented painful bone metastases of blastic or mixed lytic-blastic nature were randomly allocated into two groups; group receiving 153Sm-EDTMP and group receiving 177Lu-EDTMP. Radiopharmaceuticals were given at a dose of 37.0 MBq / kg body weight in both groups. Scores on ESAS, ECOG performance status and NRS were recorded before the intervention and following the intervention at 2, 4, 6, and 12 weeks. Hematologic toxicity was evaluated by monitoring hematologic parameters at the baseline and at 1, 3, 6, and 8 weeks after the intervention.Results: Fifty patients, 31 (62 %) females and 19 (38 %) males with the mean age of 66.08 ± 4.53 years were recruited. The baseline means and standard deviations for pain intensity as measured by the NRS were 8.4 ± 1.47 and 8.36 ± 1.43 in 153Sm-EDTMP- and 177Lu-EDTMP-treated subjects respectively. Patients of both groups showed significant alleviation of pain observed from the 2nd week (first follow up session) and continuing to the 12th week after treatment . No difference in response to the two radiopharmaceuticals were seen regarding their efficacy in pain alleviation (P < 1.0). Baseline “symptom distress scores” drawn from the ESAS-r in 153Sm-EDTMP- and 177Lu-EDTMP-treated groups were 5.5 ± 2.1 and 5.4 ± 2.1, respectively. The scores significantly improved in both groups with the most marked rate of improvement achieved within the first two weeks after treatment. The scores continued to improve until the 12th week of follow-up (P < 1.0, non-significant [ns]). Functional status as measured by ECOG performance status scores improved in both groups over the follow up period. Baseline scores on ECOG performance status in 153Sm-EDTMP- and 177Lu-EDTMP-treated groups were 2.5 ± 1.3 and 2.5 ± 1.3 (mean ± standard deviation). At 3 months post-treatment scores improved to 1.6 ± 0.6 and 1.6 ± 0.6 respectively (P < 1.0, n.s.). Conclusions: 153Sm-EDTMP and 177Lu-EDTMP are safe and effective radiopharmaceuticals in palliation of cancer pain from multiple skeletal metastases of blastic and mixed lyticblastic nature.

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

Abstract: Prior administration of Sm-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.

Cited by 10 publications

References 10 publications

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

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

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

153Sm-EDTMP and 177Lu-EDTMP are equally safe and effective in pain palliation from skeletal metastases

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