E-ISSN 2305-1620 | ISSN 2221-0288
 

Case Report 


istan Journal of Nuclear Medicine (Volume 7, issue 1)

https://doi.org/10.24911/EJBCMS.7.7

Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report

Tatiana Kochetova*, Valeriy Krylov

Nuclear Therapy Department, A Tsyb Medical Radiological Research Center, National Medical Research Radiological Center Ministry of Health of the Russian Federation

Address for correspondence

Tatiana Kochetova

249034 Koroleva 4

Obninsk, Kaluga region,

Russian Federation

Tel: +7 (919) 0345838,

Fax: +7 (484) 3993344

Email: tat_mail@inbox.ru


ABSTRACT

Ra-223 therapy is recommended for Castration Resistant Prostate Cancer (CRPC) patients with bone metastases. The standard protocol is 5-6 cycles of therapy with 4 weeks intervals to gain survival benefit.

We report a case of a chemo-naïve CRPC patient who after 1.5 years of androgen-deprivation therapy had widespread bone metastases, PSA of 4186 ng/ml, alkaline phosphatase (ALP) at 2982 U/l, bone marrow involvement with anaemia and thrombocytopaenia. 223RaCl2 therapy was started in August 2014. After the first two cycles of 223RaCl2 PSA dropped to 70 ng/ml, ALP to 877 U/l. The third cycle was delayed for 5.5 months due to technical reasons. Unexpectedly, during Ra-223 therapy interruption the positive changes were still ongoing. PSA-level decreased further, to 0.28 ng/l and ALP to 254 U/l. Hb level increased from 101 to 125 g/l, PLT from 105 to 180x109/l. After the interruption the patient received 4 planned cycles. Control bone scan after the 4th cycle revealed pathological uptake only in shoulder joints and sternum. In the follow-up period the patient demonstrated minimal disease signs: with normal ALP level, PSA 0.11 ng/ml.

Ra-223 Therapy can give anti-tumour effect, as can be seen from the significant decrease in the PSA level. Breaks in Ra-223 Therapy are not dramatic. After interruption, it can be continued again. This fact can be taken into account while planning therapy. As shown here, clinical cases such the one we have reported, may allow a degree of flexibility to the standard recommendations on a case to case basis.


Keywords:

Radium-223, Castration resistant prostate cancer, Bone metastases

INTRODUCTION

Ra-223 chloride became a gold standard of treatment of Castration Resistant Prostate Cancer (CRPC) with bone metastases. ALSYMPCA trial and later investigations have shown benefit in overall survival in patients who received Ra-223 treatment compared with the placebo group [1, 2]. The standard protocol recommends 6 cycles of radium-223 therapy (55 kBq/kg dose) at 4-weekly intervals [3]. Survival benefit has been shown in patients who have completed all 6 cycles compared with those who received less than 5 cycles [4]. Sometimes, the following cycle can be delayed due to different reasons. The influence of these delays on the treatment outcome remains unclear. There are some retrospective data which have shown that there is no significant difference in the number of completed cycles or the median overall survival between those patients, who received their treatment in a planned way and those who experienced a 4-week treatment delay. Moreover, patients with unexpected treatment delay have shown significantly longer median progression free survival [5].

Circumstances may interfere with the treatment schedule, which may beg the question: what is better for the patient, switch to alternative treatment method or restart Ra-223 treatment? We present a clinical case of long-term treatment delay of 5.5 months between the 2nd and 3rd cycles where despite the delay the patient showed clinical benefit.

CASE REPORT

A 56-year-old man with high-grade prostate adenocarcinoma (Gleason 8) with widespread multiple bone metastases was diagnosed with CRPC after 1.5 years of initially successful androgen-deprivation therapy. After a relatively long period of stable disease under standard hormonal therapy, his PSA started to rise. The best standard-of-care at that time (February, 2014) was chemotherapy; however, the patient refused the treatment and opted for the then new investigational treatment with Ra-223. But as a result of a significant delay (6 months) in the starting date of the clinical trial, his PSA and ALP levels rose quite dramatically and he became mildly symptomatic for which he was prescribed analgesics. At the time of the start of treatment, his bone scan showed a “superscan” appearance, PSA was >4000 ng/ml and ALP level nearly reached 3000 (normal range: 0-120 U/l). Moreover, there was bone-marrow involvement, haemoglobin level dropped to 101 g/l, and platelet count dropped to 105 x109/l. In August 2014, the patient received his first cycle of Ra-223, which was well tolerated, followed by the second cycle 4 weeks later. After the start of the treatment, the ALP level started to decline, and in 2 months time dropped from 2982 to 878 U/l (Figure 1); PSA level fell from 4186 to 70 ng/ml (Figure 2), Hb level and PLT counts remained on the border of acceptable (Figure 3 and 4).

Unfortunately, the patient couldn’t receive his third cycle of Ra-223 in time, due to unexpected supply disruption. After the first two cycles, there was clearly a good biochemical response but both tumour marker levels (PSA and ALP), remained much higher than normal. In this situation it was difficult to predict which was the better of the two options: 1) switch to chemotherapy (abiraterone and enzalutamide were not available) or 2) stay without any kind of treatment until supplies were restored. However, the patient himself refused to undergo chemotherapy again and decided to wait until the supply was restored, which period lasted for 5.5 months. Unexpectedly however, Ra-223 continued to have a beneficial effect. During the shortage period, the patient didn’t receive any kind of treatment except for continuing with his standard androgen deprivation therapy (Zoladex). Despite the fact that the patient was neither given chemotherapy nor any of the new hormone therapies, his PSA level continued to fall, and was measured at 0.28 ng/ml at the 5th month of supply interruption (Figure 2). ALP level also declined, but was sill double the upper limit of the normal range (Figure 1). Thus, when the supplies restarted he received 4 additional cycles, so his treatment which initially started in August 2014 completed late by June 2015.

Figure 1. ALP level dynamics in pretreatment and treatment period. Dates, when the patient received Ra-223 marked with red dots

Figure 2. PSA level dynamics in pretreatment and treatment period. Dates when the patient received Ra-223 marked with red dots

Figure 3. Hb level dynamics in pretreatment and treatment periods. Dates, when the patient received Ra-223 marked with red dots

Figure 4. PLT counts in pre-treatment and treatment periods. Dates, when the patient received Ra-223 marked with red dots

The outcome of such unusual treatment schedule was nonetheless excellent with the bone scan, which was performed in April 2015 (after the 4th cycle of treatment), demonstrating nearly complete response, particularly when compared with the pre-treatment scan which had shown widespread skeletal involvement (Figure 5) and on the control bone scan only slight increase in 99mTc-MDP uptake in the shoulder joints and sternum could be seen (Figure 6).

Figure 5. Pre-treatment whole-body bone scan with 99mTc-MDP on 7 Aug 2014 in the anterior (left) and posterior (right) projections showing “superscan” appearance

Figure 6. Post-treatment whole-body bone scan with 99mTc-MDP after the 4th treatment cycle on 21 Apr 2015 in the anterior (left) and posterior (right) projections showing almost complete resolution

This case also demonstrated a relatively long progression-free survival of 37 months duration. In September 2017, the PSA level again started to rise with the 11C-choline PET-CT revealing bone metastases only in the shoulder joints.

DISCUSSION

The Ra-223 treatment schedule was approved in randomized placebo-controlled trials. The ALSYMPCA trial demonstrated acceptable safety profile and positive influence on survival [1]. In fact, the treatment schedule was drown empirically. Investigators stay on the idea, that the number of completed cycles can influence on survival independently from the PSA, ALP and radiologic dynamics [4]. The optimal time between consecutive cycles of Ra-223 remains unclear, different time schedules are not investigated. This clinical case demonstrated some unexpected advantages of long intervals between treatment cycles. When the patient started his Ra-223 therapy his blood counts were not very good, and he couldn’t be predicted to be able to complete all 6 cycles of the therapy. But during the treatment shortage his blood counts became normal. After resumption of the treatment, there was a slight decline in the platelet counts and haemoglobin level, which reflects the adverse effect of Ra-223. Thus, the unexpected shortage had some advantages in this clinical case.

A previous report suggests that longer intervals between therapy cycles can prolong progression-free survival [5]. This clinical case has demonstrated possible advantages of long treatment intervals for patients with widespread bone disease and bone marrow involvement and a high risk of haematologic adverse events. In all reported cases the treatment delays were unplanned, but outcomes of these cases were positive. Thus, it appears that in some cases, the treating physician may consider changing Ra-223 treatment schedule in order to allow bone marrow to recover and prevent possible haematotoxicity.

On the merit of this individual case, it may be assumed that in patients who show a good response to Ra-223, the occasional unavailability of Ra-223 for the following cycle, there may not be a need to switch to other kinds of therapy. It is however important to change treatment strategy in cases where there is evidence of disease progression.

CONCLUSION

This case report has demonstrated that Ra- 223 acts much longer than 28 days, and has underscored the fact that treatment delays may not have a significant influence on overall patient survival. Moreover, in some clinical cases it may be better to lengthen the interval between consecutive therapy cycles, particularly in patients with widespread bone metastases and a low bone marrow reserve.

Acknowledgement

This patient received Ra-223 according to the clinical study protocol NCT01516762, which was sponsored by Bayer.

REFERENCES

  1. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al.; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369(3):213-23.
  2. Saad F, Carles J, Gillessen S, Heidenreich A, Heinrich D, Gratt J, et al. Radium-223 International Early Access Program Investigators. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol 2016; 17(9):1306–16; https://doi.org/10.1016/S1470- 2045(16)30173-5
  3. Parker C, Gillessen S, Heidenreich A, Horwich A. Cancer of the prostate: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26(Suppl 5):v69–77.
  4. Saad F, Keizman D, O’Sullivan J, Carles J, Wirth M, Gillessen S, et al. Analysis of overall survival by number of radium-223 injections received in an international expanded access program (iEAP). J Clin Oncol 2016; 34(15):5082–5082.
  5. Fosbøl MØ, Petersen PM, Daugaard G, Holm S, Kjaer A, Mortensen J. Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients. Ann Nucl Med 2018; 32: 16–21.


How to Cite this Article
Pubmed Style

Tatiana Kochetova, Valeriy Krylov. Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report. Pak J Nucl Med. 2017; 7(1): 38-41. doi:10.24911/PJNMed.7.7


Web Style

Tatiana Kochetova, Valeriy Krylov. Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report. http://www.pjnmed.com/?mno=302240 [Access: November 17, 2018]. doi:10.24911/PJNMed.7.7


AMA (American Medical Association) Style

Tatiana Kochetova, Valeriy Krylov. Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report. Pak J Nucl Med. 2017; 7(1): 38-41. doi:10.24911/PJNMed.7.7



Vancouver/ICMJE Style

Tatiana Kochetova, Valeriy Krylov. Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report. Pak J Nucl Med. (2017), [cited November 17, 2018]; 7(1): 38-41. doi:10.24911/PJNMed.7.7



Harvard Style

Tatiana Kochetova, Valeriy Krylov (2017) Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report. Pak J Nucl Med, 7 (1), 38-41. doi:10.24911/PJNMed.7.7



Turabian Style

Tatiana Kochetova, Valeriy Krylov. 2017. Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report. Pakistan Journal of Nuclear Medicine, 7 (1), 38-41. doi:10.24911/PJNMed.7.7



Chicago Style

Tatiana Kochetova, Valeriy Krylov. "Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report." Pakistan Journal of Nuclear Medicine 7 (2017), 38-41. doi:10.24911/PJNMed.7.7



MLA (The Modern Language Association) Style

Tatiana Kochetova, Valeriy Krylov. "Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report." Pakistan Journal of Nuclear Medicine 7.1 (2017), 38-41. Print. doi:10.24911/PJNMed.7.7



APA (American Psychological Association) Style

Tatiana Kochetova, Valeriy Krylov (2017) Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report. Pakistan Journal of Nuclear Medicine, 7 (1), 38-41. doi:10.24911/PJNMed.7.7





Most Viewed Articles
  • Lactate dehydrogenase (LDH) as predictive factor of the pain free syndrome duration after radionuclide treatment of bone metastases in patients with breast cancer
    Nigora Rasulova, Dauranbek Arybzhanov, Vladimir Lyubshin, Abdulla Abdikhakimov, Shamsutdin Sagdullaev,Sherzod Nishonov, Gayrat Arifhodjaev,Yuliya Shakirova, Valery Krylov, Marat Khodjibekov
    Pak J Nucl Med. 2016; 6(1): 11-18
    » Abstract

  • Radiosynoviorthesis in pigmented villonodular synovitis using Re-188 labelled tin colloid: a case report
    Aakif U Khan, Hameedullah, Abdul Saeed Shah, Muhammad Rauf Khattak
    Pak J Nucl Med. 2016; 6(1): 42-47
    » Abstract

  • Whither Nuclear Medicine Training in Pakistan?
    Durr-e-Sabih
    Pak J Nucl Med. 2016; 6(1): 1-2
    » Abstract

  • Multifocal osteomyelitis on bone scan performed for mandibular mass with uncertain malignancy
    Salah Oueriagli Nabih, Hassna El Guerrouj, Imad Ghfir, Nouzha Ben Raïs
    Pak J Nucl Med. 2016; 6(1): 72-74
    » Abstract

  • Functional ectopic cystic parathyroid adenomas: case reports and literature review
    Nigora Rasulova, Qaisar Hussain Siraj, Amir Javaid, Anwar Al-Banna
    Pak J Nucl Med. 2016; 6(1): 63-68
    » Abstract

  • Unusual spinal metastases from an adenoid cystic carcinoma of the maxillary sinus seen on a bone scan: a case report
    O Ait Sahel, I Ghfir, H Guerrouj, Y Benameur, N Benraiss
    Pak J Nucl Med. 2016; 6(1): 48-52
    » Abstract

  • Assessment of renal parenchymal damage by DMSA after PCNL procedure in children using adult-sized equipment
    Mohammad Sohaib, Manoj U Shenoy, Michael J Kellett, Patrick G Duffy, Isky Gordon
    Pak J Nucl Med. 2016; 6(1): 19-24
    » Abstract

  • Estimation of time for release of patients after the administration of I-131 to thyrotoxicosis patients
    Muhammad Akhtar, Jawad Akhtar Hussain, Akbar Ali, Sheraz Akhtar
    Pak J Nucl Med. 2016; 6(1): 3-10
    » Abstract

  • SPECT/CT imaging of primary mediastinal goitre: case report and literature review
    Imad Ghfir, Abdallah Achir, Hasnae Guerrouj, Salah Nabih Oueriagli, Omar Ait Sahel, N Benraïs Aouad
    Pak J Nucl Med. 2016; 6(1): 53-58
    » Abstract

  • Unsuspected chronic multifocal osteomyelitis diagnosed on a whole-body 18F-FDG PET/CT scan
    Qaisar Hussain Siraj, Amir Javaid, Khattab Khaled, Anwar Al-Banna
    Pak J Nucl Med. 2016; 6(1): 75-78
    » Abstract

  • Most Downloaded
  • Successful Ra-223 treatment with a long interval between the second and the third cycles: a case report
    Tatiana Kochetova, Valeriy Krylov
    Pak J Nucl Med. 2017; 7(1): 38-41
    » Abstract » doi: 10.24911/PJNMed.7.7

  • Clinical characteristics and long-term outcome of patients with differentiated carcinoma of thyroid with bone metastases: a retrospective study
    Sadaf Tufail Butt, Shazia Fatima, Noreen Marwat, Kahkashan Mir, Ayesha Ammar, Mohammad Faheem
    Pak J Nucl Med. 2017; 7(1): 34-37
    » Abstract » doi: 10.24911/PJNMed.7.6

  • Estimation of time for release of patients after the administration of I-131 to thyrotoxicosis patients
    Muhammad Akhtar, Jawad Akhtar Hussain, Akbar Ali, Sheraz Akhtar
    Pak J Nucl Med. 2016; 6(1): 3-10
    » Abstract

  • Cutaneous flow pattern of primary lymphoedema
    Qaisar Hussain Siraj
    Pak J Nucl Med. 2017; 7(1): 42-43
    » Abstract » doi: 10.24911/PJNMed.7.8

  • Radiosynoviorthesis in pigmented villonodular synovitis using Re-188 labelled tin colloid: a case report
    Aakif U Khan, Hameedullah, Abdul Saeed Shah, Muhammad Rauf Khattak
    Pak J Nucl Med. 2016; 6(1): 42-47
    » Abstract

  • Functional ectopic cystic parathyroid adenomas: case reports and literature review
    Nigora Rasulova, Qaisar Hussain Siraj, Amir Javaid, Anwar Al-Banna
    Pak J Nucl Med. 2016; 6(1): 63-68
    » Abstract

  • Multifocal osteomyelitis on bone scan performed for mandibular mass with uncertain malignancy
    Salah Oueriagli Nabih, Hassna El Guerrouj, Imad Ghfir, Nouzha Ben Raïs
    Pak J Nucl Med. 2016; 6(1): 72-74
    » Abstract

  • SPECT/CT imaging of primary mediastinal goitre: case report and literature review
    Imad Ghfir, Abdallah Achir, Hasnae Guerrouj, Salah Nabih Oueriagli, Omar Ait Sahel, N Benraïs Aouad
    Pak J Nucl Med. 2016; 6(1): 53-58
    » Abstract

  • Pulmonary arteriovenous malformation diagnosed on a 18F-fluorodeoxyglucose PET/CT scan
    Khattab Khaled, Amir Javaid, Qaisar Hussain Siraj
    Pak J Nucl Med. 2016; 6(1): 69-71
    » Abstract

  • Unsuspected chronic multifocal osteomyelitis diagnosed on a whole-body 18F-FDG PET/CT scan
    Qaisar Hussain Siraj, Amir Javaid, Khattab Khaled, Anwar Al-Banna
    Pak J Nucl Med. 2016; 6(1): 75-78
    » Abstract

  • Most Cited Articles