Case sharing Abiraterone continues to relieve PSA deeply, and the quality of the original research is more guaranteed

Prostate cancer is a serious threat to the health of middle-aged and elderly men in China.
Among them, the diagnosis and treatment of metastatic hormone-sensitive prostate cancer (mHSPC) is complicated, and most patients will eventually progress to metastatic castration-resistant prostate cancer (mCRPC).
Clinicians need to combine evidence-based Medical evidence and the comprehensive situation of the patient to formulate treatment strategies
.

Zeke® (abiraterone acetate tablets) has been unanimously recommended by domestic and foreign guidelines for the treatment of mHSPC and mCRPC patients due to its excellent curative effect
.

This time, I will bring you 2 cases from the real world to share with readers
.

Case 1 male with medical history, 80 years old, chief complaint: weakness of both lower limbs with limited mobility, difficulty in urination and defecation
.

Hospital: The Second Affiliated Hospital of Chongqing Medical University
.

Diagnosis: Prostate cancer with multiple bone metastases, lung metastases, hypertension, depression
.

Auxiliary examination of serum PSA: 336.
4ng/ml
.

Testosterone: 489.
7ng/ml
.

Imaging examination: 2016.
11.
23.
The patient underwent pelvic MRI enhancement + cervical spine MR + thoracic MR examination.
The examination found diffuse prostate disease.
Considering that prostate cancer with cervical, thoracic, lumbar, sacral and pelvic multiple metastases is likely to be bilateral The seminal vesicles are invaded
.

Enlarged pelvic lymph nodes
.

2016.
11.
23 The patient underwent vertebral CT plain scan + three-dimensional reconstruction examination.
The examination found T2, T3 vertebral bone destruction and soft tissue masses, combined with medical history to consider metastasis, and T3 level spinal cord compression
.

Nodules in the right chest wall, fibrous foci with thickening of the pleura may be, except for metastases
.

2016.
11.
28 The patient underwent an enhanced chest CT examination, and the examination found infectious lesions in the left lung with metastases
.

The left hilar and mediastinal lymph nodes showed a slight enlargement
.

Bilateral pleural effusion, mainly on the left side
.

The sixth posterior rib on the left is destroyed and multiple thoracic vertebrae are damaged with soft tissue masses.
Considering that multiple metastases may be large
.

2016.
11.
25 The patient underwent whole-body bone imaging examination, and the examination found that there were multiple ribs on both sides, multiple spine, left sacroiliac joint, right iliac joint, left upper femur, and right upper fibula with different forms of radioactive concentration.
Poly
.

Abnormal images of whole body bone imaging, metastatic bone tumors
.

Figure 1 Imaging diagnosis Figure 2 Percutaneous puncture and pathological diagnosis of bone scan results: T3 spinal canal metastatic prostate cancer
.

The diagnosis result is metastatic hormone-sensitive prostate cancer
.

Treatment process 1.
Initial treatment plan: ①Percutaneous puncture T2, T3 vertebroplasty + radioactive seed implantation + percutaneous endoscopic thoracic spine tumor lesion removal + spinal canal decompression; ②Combined androgen block (CAB) plan: Flutamide + Leuprolide
.

2.
In November 2016, the patient received flutamide + androgen deprivation therapy (ADT) after surgery, and the PSA decreased
.

In September 2017, 9 months after treatment, PSA gradually increased and the disease progressed to the mCRPC stage
.

Figure 3 PSA level 3.
From August 2018 to January 2021, the CAB regimen was adjusted to abiraterone acetate + ADT, PSA declined rapidly, deep remission, and stable disease
.

Figure 4 Case analysis of PSA level: The patient was diagnosed with mHSPC.
According to the analysis of the condition, the patient had obvious chest and back pain, limited mobility of the lower limbs, difficulty in urination, and compression of the spinal cord.
Related examinations indicated metastatic bone tumors, and palliative surgery is feasible Treatment
.

After full communication with the patient’s family, percutaneous puncture T2 and T3 vertebroplasty + radioactive seed implantation + percutaneous endoscopic thoracic tumor removal + spinal canal decompression surgery treatment, the traditional CAB regimen (flutamide + Leuprolide)
.

After 9 months of treatment, the patient's disease progressed to the mCRPC stage, which makes us rethink the choice of initial treatment
.

In terms of mechanism of action, CAB therapy aims to reduce the effect of androgens on prostate cancer cells.
However, traditional CAB therapy cannot completely block androgen synthesis from adrenal glands and prostate cancer cells, resulting in androgens remaining in prostate tissue.
Will stimulate prostate cancer 1,2
.

In terms of efficacy, a meta-analysis of 27 clinical trials3 compared the efficacy of traditional CAB regimen and ADT alone in the treatment of advanced prostate cancer in 8,000 patients.
The results showed that the overall survival (OS) of traditional CAB regimen was better than that of ADT alone.
) No significant difference, limited benefits
.

The patient was replaced with abiraterone acetate + ADT treatment in August 2018, and PSA dropped rapidly, below the minimum detection limit of 0.
09 ng/ml and has continued to this day
.

At present, the patient's lower limbs move freely, the size and urination are normal, the bone and lung metastases are stable, and the patient's quality of life is significantly improved, and the benefits are significant
.

Abiraterone acetate is a CYP17 inhibitor that can completely inhibit androgen synthesis from the root cause and significantly delay the disease progression of mCRPC patients4,5
.

COU-AA-302 study 6 showed that compared with the control group, abiraterone acetate significantly prolonged the OS of mCRPC patients by 34.
7 months (vs.
30.
3 months, HR=0.
81, P=0.
0033)
.

Especially for patients with mCRPC with mild early disease and no chemotherapy, the OS was significantly prolonged by 7 (53.
6 vs.
41.
8 months, HR=0.
61, P=0.
006)
.

Figure 5 COU-AA-302 research results Case provider: Professor Liu Chuan, Professor Liu Chuan, Doctor of Medicine, Master's Tutor, Deputy Director, Department of Urology, Second Affiliated Hospital of Chongqing Medical University, Member of the Committee of Urinary and Male Reproductive Tumors, Chinese Anti-Cancer Association, China Anti-Cancer Association Member of the Bladder Cancer Group of the Urinary and Male Reproductive Tumors Committee of the Cancer Society Member of the Translational Medicine Group of the Urology Committee of the Chinese Association of Integrative Medicine The deputy head of the oncology group of the committee, the secretary of the Urology Committee of the Minimally Invasive Branch of the Chongqing Medical Association, commented (Dong Qiang) After the patient was diagnosed with mHSPC, he was treated with traditional CAB regimen, and the disease quickly progressed to castration in less than one year Resistance phase (mCRPC)
.

After the patient entered the mCRPC stage, PSA was not effectively controlled and continued to rise
.

After the patient adjusted the treatment plan in time and switched to abiraterone acetate treatment, the PSA was deeply relieved
.

With the development of new endocrine therapy drugs such as abiraterone acetate, it has gradually replaced the status of traditional endocrine therapy drugs and has become the first-line treatment plan for mCRPC recommended by guidelines 8-12 at home and abroad
.

Early treatment of mCRPC patients with abiraterone acetate can bring significant survival benefits, delay disease progression, and have good long-term safety
.

Figure 6 Experts recommended by domestic and foreign guidelines: Professor Dong Qiang Professor Dong Qiang, Chief Physician/Professor of Urology, PhD supervisor, Director of Department of Surgery/Department of Surgery, West China Hospital, Sichuan University Director of Urology and Andrology Laboratory, Institute of Urology, West China Hospital, Sichuan University Sichuan Provincial Academic and Technical Leader Cao Guangbiao, Visiting Professor of Surgery, Chinese University of Hong Kong, winner of the 4th "National Famous Doctor·Excellent Demeanor" Received in 1998, PhD in Urology, West China School of Clinical Medicine, Sichuan University, 2002-2004, Biomedical Research Center, U.
S.
Population Commission He also studied as a postdoctoral fellow at Rockefeller University.
During the period, he studied in the Department of Urology at New York Presbyterian Hospital, Cornell University School of Medicine, New York, USA in 2004
.

Case 2 A 70-year-old male with medical history, chief complaint: B-ultrasound found that the prostate occupied 4 days
.

Past history: history of right rib fracture
.

Physical examination: Anal digital examination showed that the prostate is 4×5cm in size, hard in quality, shallow in the central groove, and palpable induration on the left lobe
.

Auxiliary examination on May 25, 2020, B-ultrasound showed: 18×14mm hypoechoic nodules in the periphery of the prostate
.

PSA on May 30, 2020: tPSA=739.
10ng/ml, fPSA>50ng/ml
.

CT on June 2, 2020 showed: chronic bronchitis, emphysema, bullae in the upper lobe of the right lung, and small nodules in the upper lobe of the right lung
.

MRI showed: Consider prostate cancer, multiple metastases
.

Figure 7 MRI results bone scan shows: consider multiple tumor bone metastases
.

On June 4, 2020, a transperineal prostate biopsy under general anesthesia was performed: 12+3 needles were punctured, and 3 needles were added to the left peripheral nodule
.

Pathological suggestion: (prostate puncture tissue) all points are adenocarcinoma, Gleason score 5+4=9 points
.

Diagnosis (high risk) metastatic hormone-sensitive prostate cancer (T4NxM1b)
.

After treatment 1.
From June to August 2020, the treatment of imitation abiraterone + leuprolide + zoledronic acid was given, the PSA level plummeted, and tPSA=1.
51ng/ml was rechecked on August 12, 2020
.

Figure 8 PSA and testosterone levels 2.
Liver function examination on August 18, 2020 showed that alanine aminotransferase (ALT) was 774 U/L and aspartate aminotransferase (AST) was 366 U/L, both of which were elevated, and the patient developed liver function Incomplete
.

3.
The patient was admitted to the hospital for hepatoprotective treatment and was given diammonium glycyrrhizinate capsules and polyene phosphatidylcholine capsules
.

After the patient was discharged from the hospital on August 27, 2020, the imitation abiraterone was replaced with the original abiraterone acetate.
The liver enzyme index decreased rapidly, and since follow-up, the level has remained stable and low
.

PSA and testosterone levels are well controlled
.

Figure 9 ALT and AST levels Figure 10 PSA and testosterone level case analysis After the patient was diagnosed as a high-risk mHSPC patient, it was assessed that he should not undergo radical surgery, and endocrine therapy was considered
.

At present, domestic and foreign guidelines recommend ADT+abiraterone+prednisone as the first-line endocrine therapy for patients with mHSPC
.

The patient was first treated with the imitation abiraterone.
Although the PSA level decreased, the patient's ALT and AST increased, and liver damage occurred
.

For patients with hepatic insufficiency during treatment with abiraterone, serum transaminase levels should be monitored: once before medication, every 2 weeks for the first 3 months after medication, and once a month thereafter
.

Blood pressure, serum potassium, and fluid retention should be monitored monthly
.

In addition, according to the different Child-Pugh scores of liver function, the dosage is adjusted
.

For patients with hepatotoxicity during treatment (ALT and/or AST>5×ULN or total bilirubin>3×ULN), the drug should be temporarily interrupted and the dose should be adjusted.
At the same time, monitor serum transaminase and bilirubin levels
.

The patient was admitted to the hospital for hepatoprotective treatment.
After discharge, the imitation abiraterone was replaced with the original abiraterone acetate.
The liver enzyme index decreased rapidly and remained stable, which suggests that there is a difference between our generic drug and the original drug
.

Generally, the bioavailability of a generic drug is considered to be bioequivalence within 80%~125% of the bioavailability of the original drug.
However, the determination of bioequivalence will lead to the bioequivalence of the generic drug and the original drug in principle.
There are differences in availability, and will lead to greater differences in bioavailability between generic drugs, so bioequivalence≠clinical equivalence13
.

In addition, bioequivalence has limitations in research subjects
.

Except for special drugs such as anesthetics, class I psychiatric drugs, highly toxic drugs, women and children drugs, the bioequivalence test of general drugs selects healthy male subjects between 18 and 40 years old.
Therefore, the results are only representative of health.
The bioavailability of the population cannot be directly applied to patients in the real world
.

Case provider: Dr.
Sun Liguo, Dr.
Sun Liguo, Director of the Department of Urology, Changshu Second People's Hospital, Member of the Urology Branch of Suzhou Medical Association Member of the Andrology Branch of Suzhou Medical Association Member of the Andrology Branch of Suzhou Medical Association Deputy Chairman of the Urology Branch of Changshu Medical Association Main Research Area: Urology Minimally invasive treatment of stones, application of laparoscopic technology in urinary tract tumors and reconstruction, and treatment of critically ill patients
.

Comment (Wang Yujie) Although generic drugs have passed the consistency evaluation, there are still situations that are not suitable for replacing original drugs, such as high-risk patients, high-risk diseases or high-risk drugs
.

In this case, the patient suffered liver damage from using the generic abiraterone.
The liver enzyme level returned to normal after replacing the original abiraterone acetate, which is considered to be due to the adverse effects of the generic drug
.

The treatment goal of mHSPC is to extend the time to progress to metastatic castration-resistant prostate cancer (mCRPC) and prolong patient survival
.

However, if the patient affects the follow-up treatment due to adverse reactions, the gain will not be worth the loss
.

The advantage of imitation products is that they are cheap, but the only advantage is that they are cheap, and their efficacy and safety are not exactly the same as those of the original drug
.

In clinical practice, how to balance economics with efficacy and safety is what every clinician should think about and must be passed on to patients
.

Reviewer: Professor Wang Yujie, Professor Wang Yujie, Ph.
D.
Chief Physician Director of Urology Center of the First Affiliated Hospital of Xinjiang Medical University Chairman of Xinjiang Anticancer Association Urinary and Male Reproductive Tumor Professional Committee Chairman of Xinjiang Medical Association Organ Transplant Professional Committee Chairman of Chinese Medical Doctor Association Urologists Member of the Sub-Committee Member of the Urology Professional Committee of the Chinese Research Hospital Association Standing Member of the Urology Branch of the China Medical Care International Exchange and Promotion Association Member of the Renal Transplant Professional Committee of the China Healthcare International Exchange Promotion Association Member of the Endoscopy Training Base of the Ministry of Health Xinjiang Urology Endoscopy Base Director Zazazeke® (Abiraterone Acetate Tablets) is a recognized first-line treatment for advanced prostate cancer in the field of urinary tumors, and its efficacy and safety have been widely recognized in clinical practice
.

The above two cases remind us that for the treatment of mHSPC and mCRPC, the original abiraterone acetate should be used as soon as possible, so as to deeply relieve PSA and reduce the incidence of adverse events, thereby improving the quality of life of patients and prolonging the survival of patients
.

Remarks: Abiraterone acetate tablet is referred to as Abiraterone in the text.
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3.
Prostate Cancer Trialists' Collaborative Group, Maximum androgen blockade in advanced prostate cancer: anoverview of the randomised trials, the Lancet, Vol 355, April 29, 2000.
4.
ChenY, et al.
Lancet Oncol, 2009;10 (10): 981 -991.
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AngJE, et al.
Br J Cancer.
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Lancet Oncol, 2015, 16(2): 152 -160.
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MillerK, et al.
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Guidelines on Prostate Cancer.
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NCCN Clinical Practice Guidelines inOncology(NCCN Guidelines®) .
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v2.
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2020CSCO Prostate Cancer Guideline.
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2019 CUA Prostate Cancer Diagnosis and Treatment Guideline.
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Huang Lang, et al.
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