echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Active Ingredient News > Urinary System > For mHSPC patients with combined hypertension or metabolic diseases, early use of apatamine therapy can quickly reduce PSA levels and protect them for | Classic case

    For mHSPC patients with combined hypertension or metabolic diseases, early use of apatamine therapy can quickly reduce PSA levels and protect them for | Classic case

    • Last Update: 2021-03-24
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    *Only for medical professionals to read for reference.
    After two high-risk/high-tumor-burden mHSPC patients received apatamide treatment, their PSA levels dropped rapidly, with significant curative effects and good treatment safety.

    Case 1▎ Brief medical history The patient is male, 85 years old.

    History of present illness: The patient went to an outside hospital in December 2019 due to "low back pain for 2 months".
    MRI of the lumbar spine showed that there may be metastases in the 5th and 12th thoracic vertebrae, 10th thoracic vertebrae and the right hip.
    Prostate specific antigen (PSA)>100ng/ml; On December 26, 2019, the patient came to the hospital for treatment, and the prostate biopsy showed: prostate acinar adenocarcinoma, Gleason score 5+3=8, cancer tissue accounted for 20-80% of the submitted tissue; Check PSA: 138.
    9ng/ml.

    Past history: 10 years of history of hypertension, denial of history of other chronic diseases.

    The patient self-reported a "family history of tumor", the specifics are unknown.

     ▎Examination results Whole body bone imaging (2019-12-31): 9th and 10th thoracic vertebrae, left 2nd rib, right 2nd and 5th ribs, bilateral hip bones have focal and flaky radioactive concentration foci, consider Multiple bone metastases throughout the body.

    No visceral metastasis was found on whole body CT examination.

     Figure 1 Bone imaging of the patient in Case 1 before treatment.
    Preliminary diagnosis: 1.
    High-risk/high tumor burden metastatic hormone-sensitive prostate cancer (mHSPC); 2.
    Essential hypertension.

     ▎After the first phase of treatment, on December 31, 2019, the patient began to undergo androgen deprivation therapy (ADT) combined with anti-androgen therapy, supplemented with calcium, vitamin D, and bisphosphonate therapy.

    After 3 weeks of treatment (2020-1-20), the patient reported that his back pain was relieved.
    After 6 months of treatment (2020-6-1), the PSA was 5.
    97ng/ml, which did not drop to the ideal level, suggesting traditional combined androgen blockade (CAB) The treatment effect is not good, and the patient's prognosis may be poor.  In the second phase, June 1, 2020, based on the patient's willingness to seek active treatment and the need to control blood pressure, the treatment plan was adjusted to apatamide + ADT.
    After the adjustment of the plan, a rapid and deep decline in PSA occurred.
    Re-examination (2020) -12-16) PSA drops to 1.
    01ng/ml.

      Figure 2 The change of PSA during the whole course of treatment of case 1 The main adverse event reported during the treatment of the patient was skin rash.
    The details are as follows: 10 days after the start of apatamide treatment, the patient developed mild "skin allergies", which was not taken seriously and treated.
    ; At 25 days of treatment, the patient was hospitalized due to lung infection.
    After using cephalosporin antibiotics, he developed systemic allergic erythema.
    After stopping antibiotics, there was still a systemic rash.
    The patient refused to stop apatamide and was referred to a dermatology specialist hospital.
    The rash subsided after 3 days of treatment with steroid hormones; after that, he was treated with apatamide at a half-dose and applied moisturizer on a daily basis.
    No rashes or other discomforts recurred.

     Case 2▎ Brief medical history The patient is a male, 82 years old.

    Current medical history: In October 2020, the patient went to the local hospital due to "repeated fever and back pain for more than half a month".
    PSA>100ng/ml was found.
    MRI of the outside hospital showed that prostate cancer invaded the seminal vesicle gland and bladder wall, and bilateral femurs and multiple bones.
    Transfer: The patient came to the hospital for treatment on October 12, 2020, and our hospital checked PSA: 2268ng/ml.

    Past history: The patient has a history of "type 2 diabetes, grade II hypertension, coronary heart disease, and old myocardial infarction".

    There is nothing special about personal history and family history.

     ▎Examination results Prostate biopsy (2020-10-13): Prostate acinar adenocarcinoma, Gleason score 4+4=8 points, cancer tissue accounts for 60%-80% of the submitted tissue, and nerve bundle invasion can be seen.

    Whole body bone imaging (2020-10-14): sternum, multiple cervical vertebrae, sacrum, bilateral multiple ribs, bilateral hip bones, right humerus, bilateral femurs, see focal and foci-like radioactive concentrations.

     Figure 3 Bone imaging of Case 2 before initial treatment.
    Preliminary diagnosis: 1.
    High-risk/high tumor burden mHSPC; 2.
    Type 2 diabetes; 3.
    Essential hypertension; 4.
    Coronary heart disease.  ▎After treatment On October 14, 2020, the patient began to use ADT combined with apatamide therapy, calcium vitamin D and bisphosphonate therapy.

    After more than 2 months (2020-12-25), the PSA dropped to 7.
    28ng/ml, and the PSA dropped by more than 90%.

    After using apatamide for four months, she complained of relief of pain and no other discomfort.

     Figure 4 PSA changes in case 2 after apatamide treatment.
    Case provided by doctor Li Yonghong, deputy chief physician, deputy director of the Department of Urology, Sun Yat-sen University Affiliated Tumor Hospital, director of the third urinary area (prostate tumor), deputy chief physician, and master's tutor prostate cancer Single disease expert Guangdong Province Outstanding Young Medical Talent Member of the Ethics Committee of Sun Yat-sen University Tumor Hospital Member of the Standing Committee of the Asian Cryotherapy Association Member of the Standing Committee of the Chinese Physician Association Tumor Ablation Therapy Technical Expert Group Urinary Tumor Ablation Specialist Group Leader of the Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Expert Committee member Secretary of the Urogenital Tumor Professional Committee of Guangdong Anti-Cancer Association Secretary of the Guangdong Prostate Cancer Multidisciplinary Cooperation Group Secretary of the South China Surgical Robot Training Center is good at diagnosis and treatment of prostate cancer, as the first/corresponding author in European Urology, Prostate, Urology Published 10 papers in other journals, and the research results were cited by NCCN guidelines and Campbell Urology.
    Case analysis.
    High-risk/high tumor burden mHSPC patients with distant metastasis existed at the time of diagnosis.
    The prognosis is poor, and the benefits of simple ADT treatment and traditional CAB treatment are limited.
    , If the patient’s disease progresses to the stage of metastatic castration-resistant prostate cancer (mCRPC), the survival period is short.

    Therefore, the mHSPC stage is the key "decisive period" for the treatment of such metastatic prostate cancer patients.
    Early intervention with new androgen receptor (AR) inhibitors has important clinical value.

     Both patients are high-risk/high tumor burden.

    The PSA level of case 1 was still 5.
    97ng/ml at 6 months of treatment.
    Previous data analysis showed that the PSA level at 7 months of CAB treatment was a predictor of patient survival.
    If PSA could not fall below 4ng/ml, the median total of patients The survival period (OS) is only 13 months [1]. Based on the possibility of this poor prognosis and the willingness of patients to actively seek treatment, the treatment team adjusted the plan to use apatamide + ADT, which quickly reduced the patient's PSA level.

    In case 2, apatamide was used directly in the mHSPC stage, and the PSA level of the patient dropped by >90% after 2 months of treatment, showing a significant effect.

     In the key clinical phase III study TITAN, apatamide brought significant benefits to "All-comers" mHSPC patients, and the treatment group reduced the risk of imaging progression or death by 52% compared with the placebo control group.
    (HR=0.
    48, P<0.
    0001), the risk of death is reduced by 33% (HR=0.
    67, P=0.
    0053), and patients with high tumor burden have a clear OS benefit [2].

    Especially for mHSPC patients with only bone metastases, OS and imaging progression-free survival (rPFS) can be significantly improved, the risk of death is reduced by 53%, and the risk of imaging progression/death is reduced by 62%.

    The practical experience of our hospital using apatamide treatment also shows that the PSA response rate of apatamide treatment is high, and the response rate of mHSPC patients reaches 100%, and the benefit of early use is higher, which confirms the good efficacy in clinical research.
    .

    Expert comment 1 As a new type of AR inhibitor, apatamide can effectively triple-inhibit AR in terms of its mechanism of action.
    It can not only block the binding of androgens and receptors, but also effectively block the nuclear transport of AR and the binding of AR to DNA; In addition, apatamide has a higher affinity for AR, and the probability of AR mutation is lower than that of ADT alone.

    The treatment of apatamide + ADT in the TITAN study fully reflects its potent inhibition of the transformation of AR to clinical efficacy.

     In the two patients reported in this report, one was switched to apatamide after the poor response of CAB treatment, and the other was initially given apatamide after the diagnosis of mHSPC.
    The PSA level decreased rapidly and deeply, reflecting good disease control.
    The effect also shows the importance of early application of the new AR inhibitor apatamide to control the overall course of metastatic prostate cancer and improve the prognosis of patients.  Expert profile Prof.
    Qiang Dong Professor of Urology / Chief Physician, PhD Supervisor, Director of Department of Surgery, West China Hospital, Sichuan University Director of Department of Urology and Andrology, West China Hospital of Sichuan University, Visiting Professor of Surgery, Chinese University of Hong Kong, Andrology Branch of Chinese Medical Association Deputy Leader of the Prostatology Group Member of the Standing Committee of the Andrology Branch of the Chinese Medical Association Member of the Andrology Group of the Urology Branch of the Chinese Medical Association, Member of the International Exchange Committee of the Urology Branch of the Chinese Medical Association Member of the Advisory and Management Expert Committee Member of the Standing Committee of the Asian Andrology Society, Member of the Asian Andrology Society Disease Guidelines Compilation Committee Member of the China Urology and Andrology Medical Technology and Equipment Innovation Alliance Member of the National Science and Technology Term Review Committee Andrology and Sexual Medicine Term Writing Committee Deputy Editor-in-Chief Sichuan Province Medicine Chairman of the Andrology Committee and Youth Committee Member of the Minimally Invasive Urology Group of the Urology Committee of the Sichuan Medical Association Member of the Standing Committee of the Day Surgery Surgeon Committee of the Sichuan Medical Association "Chinese Andrology", "Chinese Andrology" Journal editor and executive editor of "Western Medicine" is good at minimally invasive surgical treatment of prostate diseases, diagnosis and treatment of urinary system tumors and male reproductive system diseases, and minimally invasive urology.
    "For the benefits of mHSPC, international and domestic guidelines [3] recommend this program as the standard treatment program for mHSPC patients, which can quickly and deeply reduce the patient's PSA level, prolong the hormone sensitivity time, and delay the progression of mHSPC to mCRPC.

    With the popularization and use of this program, the safety of treatment is also an issue worthy of attention of clinicians.

     In clinical studies, apatamide shows better safety.
    The overall adverse events and the incidence of serious adverse events are not significantly different from those in the placebo group.
    The adverse events that deserve special attention are mainly skin rash and hypothyroxinemia[2 ].

    In this case, a mild rash occurred during the treatment of the patient in case 1, but the rash subsided after symptomatic treatment and dose adjustment, and did not have a significant impact on the treatment.
    It was suggested that clinicians should combine the curative effect and the patient’s wishes, flexibly evaluate and deal with adverse reactions, and make treatment Maximize revenue.

    For the similar cases 1 and 2, the use of steroid-free apatamide therapy for elderly patients with more underlying diseases may help reduce the risk of adverse events and is suitable for long-term treatment of patients.

     Expert Profile Professor Qin Weijun Chief Physician, Professor, and Doctoral Supervisor Director of Urology, Xijing Hospital, Air Force Military Medical University, Vice President, Urology Branch of Chinese Medical Doctor Association, National Committee Member of Urology Branch of Chinese Medical Association, Member of Urology Professional Committee of Shaanxi Province Urology Physician of Shaanxi Province Vice President of the Society, Member of the Standing Committee of the Shaanxi Urology Branch of the Chinese Medical Association, is good at precise treatment of urinary tract tumors, prostate diseases, minimally invasive urological endoscopic techniques, and has deep knowledge in difficult operations such as vena cava thrombus.
    References: [ 1] Hussain M, Tangen CM, Higano C, et al.
    Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162)[J ].
    Journal of Clinical Oncology, 2006, 24(24): 3984-3990.
    [2] Chi KN, Agarwal N, Bjartell A, et al.
    Apalutamide for metastatic, castration-sensitive prostate cancer[J].
    New England Journal of Medicine, 2019, 381(1): 13-24.
    [3] Schaeffer E, Srinivas S, Antonarakis ES, et al.
    NCCN Guidelines Insights: Prostate Cancer, Version 1.
    2021: Featured Updates to the NCCN Guidelines[J].
    Journal of the National Comprehensive Cancer Network,2021, 19(2): 134-143.
     
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.