Radium Ra 223 Dichloride Injection: U.S. Food and Drug Administration Drug Approval Summary
Paul G. KluetzWilliam F. PierceV. Ellen MaherHui ZhangShenghui TangPengfei SongQi LiuMartin T. HaberEldon E. LeutzingerAli Al‐HakimWei ChenTodd R. PalmbyElleni AlebachewRajeshwari SridharaAmna IbrahimRobert JusticeRichard Pazdur
149
Citation
15
Reference
10
Related Paper
Citation Trend
Abstract:
On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (>10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (>10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.Keywords:
Clinical endpoint
Peripheral edema
Leukopenia
Interim analysis
Background: Infections and nutritional deficiencies are the most common causes of the leucopenia and neutropenia. In this study, we aimed to find the incidence of vitamin B12 deficiency in patients with leukopenia and neutropenia secondary to infection.Methods: Between September 2018 and December 2018, patients who were referred to Diyarbakır Children Hospital's Pediatric Hematology and Oncology Clinic for leukopenia and/ or neutropenia were thought to develop secondary to infection retrospectively evaluated.Results: Of the 60 patients that evaluated, 23(38.3%) were female and 37(61.7%) were male. The mean age±SD was 4.75±4.5 years. Severe neutropenia was detected in 5(8.3%), moderate neutropenia in 31(51.7%) and mild neutropenia in 17(28.3%) patients. Neutrophil counts were within normal limits in 7(11.7%) patients. When vitamin B12 levels were examined, 17(28.3%) patients had B12 deficiency.Conclusions: Investigation and treatment of vitamin B12 deficiency in patients with leukopenia and neutropenia may shorten the duration of cytopenia and prevent the development of secondary complications.
Leukopenia
Cytopenia
Hematology
Cite
Citations (1)
Neutropenia (or granulocytopenia) is a depression of the absolute neutrophil count to less than 1,500/mm3. Leukopenia is a related term, denoting the depression of the total leukocyte count. Although neutropenia is the most frequent cause ofleukopenia, a marked lymphocytopenia can depress the total leukocyte count in the "penic" range with a normal neutrophil count. However, a severe leukopenia always implies neutropenia.
Leukopenia
Absolute neutrophil count
Lymphocytopenia
Cite
Citations (4)
To the Editor:— Lefebvre and Hesseltine (194:15, 1965) reported a 1% incidence of transient leukopenia and neutropenia in 386 patients treated up to 14 days with metronidazole forTrichomonas vaginalisinfections. Such findings may be less alarming than implied. While it was not the primary purpose of the writer's study to statistically analyze hematopoietic effects of the agent, over 2,000 complete blood counts and 9 bone-marrow biopsies have been done in 605 treated patients with metabolic, endocrine, or autoimmune disorders. Comparable amounts of the drug were used, but for more prolonged periods than in the above study. Twelve subjects, whose white blood cell counts ( WBCs) and peripheral smears were normal prior to therapy, showed the same transient leukopenia and neutropenia described by Lefebvre and Hesseltine. However, the circulating elements spontaneously returned to normal after the 14th day of treatment, and remained so in every case. At the same time
Leukopenia
White blood cell
Bone marrow suppression
Cite
Citations (8)
To estimate the prevalence and clinical significance of leukopenia and neutropenia in patients with chronic hepatits C, to analyze the impact of different regimens of antiviral therapy by standart or induction doses of pegylated interferon alpha-2a (PegIFNalpha-2a) to optimize curative measures.24 patients with genotype 1 HCV and different therapeutic regimens of PegIFNalpha-2a were investigated with analysis of kinetics and prevalence of leukopenia and neutropenia.On an average 66,7% patients meet neutropenia during antiviral therapy, and 37,5% and 16,7% among them was the moderate and severe grade accordingly. The major prevalence of leukopenia and neutropenia was evidenced between 12 and 24 weeks of antiviral therapy, the marked severity of neutropenia was noted.It was no correlation between the prevalence of leukopenia and neutropenia and the induction treatment regimens of PegIFNalpha-2a; the tendency for more severity in patients with advanced fibrosis and cirrhosis was detected. It was no infection complications during the therapy observed so it may be provided with full doses of PegIFNalpha-2a in case of mild and moderate grades of leukopenia and neutropenia.
Leukopenia
Cite
Citations (1)
Leukopenia is an abnormal reduction of circulating white blood cells, especially the granulocytes. The term leukopenia is often used interchangeably with neutropenia. It may result from reduced production of white blood cells or increased utilization and destruction, or both. Infection, drugs, malignancy, megaloblastosis, hypersplenism and immunoneutropenia are responsible for most cases of neutropenia. Primary neutropenia is very rare. Sometimes, particularly in children, primary neutropenia is hereditary and may be associated with other developmental defects. The major danger of neutropenia is the risk of infection. Management requires identification of the cause and effective antimicrobial therapy, especially when serious systemic infection is present.
Leukopenia
Etiology
Cite
Citations (9)
Blood counts of 372 Yemenite Jews of all ages were reviewed in order to clarify the epidemiology of benign leukopenia. Twenty-one percent of the total leukocyte counts were below 5.0 x 10(3) cells/mm3. Neutropenia < 2.0 x 10(3) was present in 15.4% of the blood counts, significantly lowering the average neutrophil count in the population. There was no significant variation in the prevalence of neutropenia with age. In contrast, the average lymphocyte and erythrocyte counts were normal. We conclude that leukopenia among Yemenite Jews should be defined as neutropenia rather than leukopenia, and that the phenomenon is only half as common as was previously noted. Since the prevalence of neutropenia remains constant across all age-groups, in immigrants as well as among the Israeli-born, it is unlikely to be an acquired condition.
Leukopenia
Absolute neutrophil count
Cite
Citations (24)
bjective:To investigate the protective action of HLCJ on the leukopenia and neutropenia induced by cytoxan(CTX)in mice. Method: Models of mice with leukopenia and neutropenia here were made by injecting with CTX(100 mg/kg)for 3 days,meanwhile,these mice were treated with HLCJ and the dynamic changes of 1eukocyte and neutrophil in these mice were observed.Results:HLCJ(32g/kg,16g/kg) administrated for 8 days could improve leukopenia and neutropenia induced by CTX in mice.Oral administration of HLCJ (32g/kg,16g/kg,8g/kg) for l2 days could increase the decreased number 0f 1eukocytes and neutrophil in CTX treated mice. Conclusion: HlCJ has significant protective effect on leukopenia and neutropenia induced by cytoxan in mice.
Leukopenia
Cite
Citations (0)
Leukopenia is a common finding in the outpatient setting. It typically occurs because of a significant reduction in neutrophils, which comprise 50% to 70% of circulating leukocytes. Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1,500/mcL. Neutropenia is classified by whether it is transient or chronic. Chronic neutropenia can be further described as extrinsic or intrinsic. Extrinsic causes are varied. Intrinsic causes can include impaired proliferation and maturation of myeloid progenitor cells in the bone marrow. Assessment of patients with neutropenia should be guided by the severity on presentation. The duration of leukopenia and the clinical status of the patient also should be considered. Some patients with neutropenia can develop life-threatening bacterial infections. In neutropenic patients, the risk of febrile neutropenia should be assessed systematically. Patients with febrile neutropenia should undergo treatment with antibiotics. Other treatments are aimed at management of the underlying cause of neutropenia.
Leukopenia
Absolute neutrophil count
Cite
Citations (1)
We studied the effects of Cepharanthin (CEP) on bone marrow suppression induced by chemotherapy in 18 primary lung cancer patients (14 NSCLC, 4 SCLC). NSCLC patients received IP (IFM+CDDP) therapy and SCLC patients received ION (IFM+VCR+ACNU) therapy. For the control, we chose the first course and we administered CEP (1 mg/kg) during the second course. The rate of leukopenia and neutropenia was significantly lower during the CEP course than during the control (p less than 0.01). The recovery rate (at 3 weeks) of leukopenia and neutropenia was significantly higher during the CEP course than during the control (p less than 0.05). But, obvious effects of CEP for lymphopenia and thrombocytopenia were not obtained. Side effects by CEP were not observed in this study. These data suggest that the large dose of CEP contributes to the prevention of leukopenia, especially neutropenia, in patients who receive a sufficient amount of anticancer drugs.
Leukopenia
Bone marrow suppression
Cite
Citations (12)