Re-treatment with radium-223.

[pjoshea13]

New international study below.

"Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials."

-Patrick

ncbi.nlm.nih.gov/pubmed/289...

Ann Oncol. 2017 Oct 1;28(10):2464-2471. doi: 10.1093/annonc/mdx331.

Re-treatment with radium-223: first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases.

Sartor O1, Heinrich D2, Mariados N3, Méndez Vidal MJ4, Keizman D5, Thellenberg Karlsson C6, Peer A7, Procopio G8, Frank SJ9, Pulkkanen K10, Rosenbaum E11, Severi S12, Trigo Perez JM13, Wagner V14, Li R15, Nordquist LT16.

Author information

1

Departments of Medicine and Urology, Tulane Cancer Center, New Orleans, USA.

2

Department of Oncology, Akershus University Hospital, Lørenskog, Norway.

3

Department of Radiation Oncology, Associated Medical Professionals of New York, PLLC, Syracuse, USA.

4

Oncology Department, Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofia Hospital, University of Cordoba, Cordoba, Spain.

5

Genitourinary Oncology Service, Meir Medical Center, Kfar Saba, Israel.

6

Department of Radiation Sciences, Cancer Center Norrlands University, Umeå, Sweden.

7

Division of Oncology, Rambam Health Care Campus, Haifa, Israel.

8

Fondazione Istituto Nazionale Tumori Oncologia Medica Genitourinaria, Milan, Italy.

9

Department of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

10

Department of Oncology, Kuopio University Hospital, Kuopio, Finland.

11

Uro-Oncology Unit, Rabin Medical Center-Davidoff Center, Petah Tikva, Israel.

12

Romagnolo Scientific Institute for the Study and Care of Cancer-IRST IRCCS, Nuclear Medicine Therapeutic Unit, Meldola, Italy.

13

Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain.

14

Global Clinical Development, Bayer Pharma AG, Basel, Switzerland.

15

Global Research and Development Statistics, Bayer HealthCare Pharmaceuticals, Whippany.

16

Department of Medical Oncology, GU Research Network, LLC, Omaha, USA.

Abstract

BACKGROUND:

Six radium-223 injections at 4-week intervals is indicated for patients with castration-resistant prostate cancer and symptomatic bone metastases. However, patients usually develop disease progression after initial treatment. This prospective phase I/II study assessed re-treatment safety and efficacy of up to six additional radium-223 injections.

PATIENTS AND METHODS:

Patients had castration-resistant prostate cancer and bone metastases and six initial radium-223 injections with no on-treatment bone progression; all had subsequent radiologic or clinical progression. Concomitant agents were allowed at investigator discretion, excluding chemotherapy and initiation of new abiraterone or enzalutamide. The primary endpoint was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and prostate-specific antigen progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression.

RESULTS:

Among 44 patients, 29 (66%) received all six re-treatment injections. Median time from end of initial radium-223 treatment was 6 months. Forty-one (93%) reported ≥1 treatment-emergent adverse event. No grade 4-5 hematologic treatment-emergent adverse events occurred. Only one (2%) patient had radiographic bone progression; eight (18%) had radiographic soft tissue tumor progression (three lymph node and five visceral metastases). Median times to total alkaline phosphatase and prostate-specific antigen progression were not reached and 2.2 months, respectively. Median radiographic progression-free survival was 9.9 months (12.8-month maximum follow-up). Five (11%) patients died and eight (18%) experienced first SSEs. Median overall survival, time to first SSE, and SSE-free survival were not reached. Five (14%) of 36 evaluable patients (baseline worst pain score ≤7) had pain progression. After 2 years of follow-up, 28 (64%) patients died, and the median overall survival was 24.4 months.

CONCLUSIONS:

Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.

KEYWORDS:

bone metastases; injections; prostate; radium-223; re-treatment; safety

PMID: 28961839 DOI: 10.1093/annonc/mdx331

[YostConner]

Thanks for posting this. I've had one radium 223 injection so far, but this is something my husband and I have already discussed theoretically. I've bookmarked the article.

[Dan59]

Thanks for posting this Patrick, It is usefull to know we can get more than one cycle of rad223 if we need it.

[Hidden]

Good that they are trialing that. I expect that a doctor could order a second round, but that insurance would be reluctant to pay for it, since there was no data to back it up - because no trial had been done yet. (even though it "seems logical")

Radium 223 in other news:

I was at a regional patients' conference for Neuroendocrine disease yesterday

(URL: roswellpark.org/netmeeting)

and the treatment that looked good (from Europe with US studies underway)

is PRRT (URL: prrtinfo.org/prrt).

It is a targeted therapy, where the target is somatostatin, and the payload is a radioactive isotope. They would love to use an alpha emitter, but have not been able to solve the twin difficulty of getting the isotope (like Radium 223) and combining it with the rest of the mechanism in time for administration. By the time part of it is assembled, it has already begun to degrade. The drug company rep said they worked on it for many years without success, and the U of Michigan asked if they could continue the effort - to which the drug company said - hey best of luck, baby. Have at it.

Sorry I don't have the drug company name, but it was one of the sponsors of the event, so it cannot be too hard to figure out.

NET is becoming a late stage development in prostate cancer. University of Iowa has the big bucks research grant for it.

[wrando]

prostatecancerinfolink.net/...

interesting link on this subject