Oral dosing of Recombinant Methioninase Is Associated With a 70% Drop in PSA in a Patient With Bone-metastatic Prostate Cancer and 50% Reduction in Circulating Methionine in a High-stage Ovarian Cancer Patient.
口服重组蛋氨酸酶与骨转移前列腺癌患者PSA下降 70% 相关，与高分期卵巢癌患者循环蛋氨酸下降 50% 相关。
- 作者列表："Han Q","Tan Y","Hoffman RM
BACKGROUND/AIM:Methionine addiction is a general and fundamental hallmark of cancer. Methionine addiction can be targeted by methionine restriction (MR). Our laboratory has studied methionine addiction in cancer and MR for almost 50 years. The present study describes oral recombinant methioninase (o-rMETase), as a supplement, to induce MR in cancer patients. PATIENTS AND METHODS:One patient, a 67-year-old female with high-stage ovarian cancer took o-rMETase twice a day at 250 units per dose for approximately one month. A second patient, a 76-year-old male with bone-metastatic prostate cancer, took o-rMETase twice a day at 250 units per dose during three months. RESULTS:The first patient's circulating methionine levels decreased 50% within 4 hours of taking 250 units of o-rMETase. The second patient's PSA dropped approximately 70% over 3 months. During this time the patient's hemoglobin increased. CONCLUSION:o-rMETase has no side effects and is potentially efficacious. Future studies involving larger cohorts of patients with high-stage cancer are required to determine if o-rMETase, as a supplement, can increase survival and improve the quality of life.
背景/目的: 甲硫氨酸成瘾是癌症的一般和基本标志。蛋氨酸成瘾可以通过蛋氨酸限制 (MR) 靶向。我们实验室对癌症和MR中的蛋氨酸成瘾进行了近 50 年的研究。本研究描述了口服重组蛋氨酸酶 (o-rMETase) 作为一种补充剂，在癌症患者中诱导MR。 患者和方法: 1 例患者，1 例 67 岁女性高分期卵巢癌患者，每天 2 次，每次 250 单位/剂，持续约 1 个月。第二例患者，76 岁男性，骨转移性前列腺癌，在三个月内每天服用o-rMETase两次，每次剂量 250 单位。 结果: 第一例患者服用 50% 单位o-rMETase后 4 小时内循环蛋氨酸水平下降 250。第二例患者的PSA在 3 个月内下降了约 70%。在此期间，患者的血红蛋白增加。 结论: o-rMETase无副作用，潜在有效。未来的研究需要涉及较大的高分期癌症患者队列，以确定o-rMETase作为补充是否可以提高生存率和改善生活质量。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.