Physicians/Clinicians - Cesium-131 Data

Radiobiology Of Proxcelan

9.7 Day half-life; 30.4 KeV average photon energy

Faster resolution of dose related morbidities

IPSS scores showed resolution of mild to moderate urinary symptoms within 4–6 months post implant supporting theoretical argument that dose related side effects dissipate faster with the shorter lived isotopes⁴.

1. Bice, W. Permanent prostate brachytherapy using Cs-131 for localized prostatic carcinoma: a phase II study. Presented at the 2008 Cesium Advisory Group Meeting November 2008. Tucson, Arizona, U.S.A.
2. Keyes M, et al. Predictive factors for acute and late urinary toxicity after permanent prostate brachytherapy: long-term outcomes in 712 consecutive patients. International Journal of Radiation Oncology, Biology and Physics 73(4):1023-32, 2009.
3. Ash D, et al. A prospective analysis of long-term quality of life after permanent I-125 brachytherapy for localized prostate cancer. Radiotherapy and Oncology 84(2):135-9, 2007.
4. Prestidge BR., Bice WS.,“Clinical outcomes of a phase II, multi-institutional Cesium –131 permanent prostate brachytherapy trial”, Brachytherapy 6, 2007, 78.

Cs-131 Monotherapy Trial

Design:

8 institutions
n = 100
Post implant CT evaluation at 2 weeks

Results:

Median follow-up time 36 months
No PSA failures by ASTRO of Phoenix/Houston definitions (right)
Prescription dose reliably delivered while V150 kept exceptionally small (below)
Prescription dose can be routinely kept to < 0.5cc of rectum (opposite corner)

Long-term survival data is now available for prostate brachytherapy with I-125 and Pd-103, which support the efficacy of brachytherapy. Clinical data indicate that brachytherapy offers success rates for early-stage prostate cancer treatment that are equal to or better than those of RP or EBRT. While clinical studies of prostate brachytherapy to date have focused primarily on results from brachytherapy with I-125 and Pd-103, management believes that these data are also relevant for brachytherapy with Cs-131. In fact, it appears that Cs-131 offers improved clinical outcomes over I-125 and Pd-103, given its shorter half-life and higher energy.

Improved patient outcomes. A number of published studies describing the use of I-125 and Pd-103 brachytherapy in the treatment of early-stage prostate cancer have been very positive. A recent study of 2,963 prostate cancer patients who underwent brachytherapy as their sole therapeutic modality at 11 institutions across the U.S. concluded that low-risk patients (who make up the preponderance of localized cases) who underwent adequate prostate implants experienced rates of PSA relapse survival of greater than 90% between eight and ten years (Zelefsky MJ, Kuban DA, et al, “Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation” International Journal of Radiation Oncology Biology Physics, Volume 67, Issue 2, 2007, 327-333).

Other recent studies have demonstrated similar, durably high rates of control following prostate brachytherapy for localized prostate cancer out to 15 years post-treatment (Sylvester J, et al. “15-year biochemical relapse free survival in clinical stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience”, International Journal of Radiation Oncology Biology Physics, Vol. 67, Issue 1, 2007, 57-64.). The cumulative effect of these series has been the conclusion by leaders in the field that brachytherapy offers a disease control rate as high as surgery, though will a lesser side-effect profile than surgery (Ciezki JP. “Prostate brachytherapy for localized prostate cancer” Current Treatment Options in Oncology, Volume 6, 2005, 389-393).

Reduced Incidence of Side Effects. Sexual impotence and urinary incontinence are two major concerns men face when choosing among various forms of treatment for prostate cancer. Studies have shown that prostate brachytherapy with existing sources results in lower rates of impotence and incontinence than surgery (Frank, Buron). Combined with the high disease control rates described in many studies, these findings have driven the adoption of brachytherapy as a front-line therapy for localized prostate cancer.

It has been noted, however, that a significant proportion of patients who undergo Iodine-125 or Palladium-103 prostate brachytherapy experience acute urinary irritative symptoms following treatment – in fact more so than with surgery or external beam radiation therapy (Frank SJ, Pisters LL, et al, “An assessment of quality of life following radical prostatectomy, high dose external beam radiation therapy, and brachytherapy iodine implantation as monotherapies for localized prostate cancer” Journal of Urology, Volume 177, 2007, 2151-2156). It has been postulated that Cesium-131, with the shortest available half-life for a low-dose rate therapy isotope, will result in a quicker resolution of these irritative symptoms based on the shorter time interval over which normal tissue receives radiation from the implanted sources.

Preliminary data drawn from several clinical studies suggest that prostate cancer patients treated with Cesium-131 do in fact experience a faster resolution of these side effects in comparison to similar studies published for other isotopes (Defoe SG, et al, “Is there a decreased duration of acute urinary and bowel symptoms after prostate brachytherapy with Cesium 131 isotope?", International Journal of Radiation Oncology Biology Physics, Volume 72 (Supplement 1), S317; Jones A, et al, "IPSS Trends for Cs-131 Permanent Prostate Brachytherapy" Brachytherapy, Volume 7, Issue 2, 194; Platta CS, et al, “Early Outcomes of Prostate Seed Implants with 131Cs: Toxicity and Initial PSA Dynamics from a Single Institution" International Journal of Radiation Oncology Biology Physics, Volume 72 (Supplement 1), 2008, S323-4). An ongoing randomized trial will seek to determine the differences in acute urinary symptoms between Cesium-131 and Iodine-125.

A Cs-131 monotherapy trial for the treatment of prostate cancer was fully enrolled in February 2007. The trial was a 100 patient multi-institutional study that sought to (1) document the dosimetric characteristics of Cs-131, (2) to summarize the side effect profile of Cs-131 treatment, and (3) to track biochemical (PSA) results in patients following Cs-131 therapy.

The investigators responsible for conducting the study have concluded based on the results of the monotherapy trial that Cs-131 is a viable alternative as an isotope for permanent seed prostate brachytherapy (Prestidge BR, Bice WS, “Clinical outcomes of a Phase II, multi-institutional Cesium-131 permanent prostate brachytherapy trial”. Brachytherapy, Volume 6, Issue 2, April-June 2007, Page 78). Some of the significant and specific findings were as follows:

Patient reported irritative urinary symptoms (IPSS Scores) were mild to moderate with relatively rapid resolution within 4-6 months. The figure below depicts the symptom scores in the Cesium-131 study as compared to published reports of patients who underwent Iodine-125 brachytherapy. Especially notable is the steep drop in the Cesium-131 group scores (purple line) as opposed to the more gradual drop in the Iodine-125 group scores (green and blue lines).
Prostate Specific Antigen, or PSA, response over 36 months has been very encouraging to date with similar tumor control rates to that of I-125. (Prestidge BR, Bice WS, “Clinical outcomes of a Phase II, multi-institutional Cesium-131 permanent prostate brachytherapy trial”. Brachytherapy, Volume 6, Issue 2, April-June 2007, Page 78). The graphic below depicts the median PSAs to date from the 100 patients Cesium-131 brachytherapy series as compared to previously published Iodine-125 series. There have been no PSA failures in the Cesium-131 monotherapy study to date.
Gland coverage was excellent and the dose delivered to critical structures outside the prostate was well within acceptable limits. (Bice WS, Prestidge BR, “Cesium-131 permanent prostate brachytherapy: The dosimetric analysis of a multi-institutional Phase II trial”. Brachytherapy 2007(6); 88-89.).

Several other series have been reported that have compared dosimetric parameters (indicators of dose) among Cesium-131, Palladium-103, and Iodine-125. These comparative studies have shown a clear advantage to Cesium-131 from a dosimetric point-of-view, in terms of successful gland coverage obtained (typically measured by D90) while keeping unnecessary gland over-dosing (typically measure by V150 or V200) to a minimum (Musmacher JS, et al, "Dosimetric Comparison of Cesium-131 and Palladium-103 for Permanent Prostate Brachytherapy" International Journal of Radiation Oncology Biology Physics, Volume 69, (Supplement 3), 2007, S730-1; Yaparpalvi R, et al, "Is Cs-131 or I-125 or Pd-103 the Ideal Isotope for Prostate Boost Brachytherapy? A Dosimetric View Point." International Journal of Radiation Oncology Biology Physics, Volume 69 (Supplement 3), 2007, S677-8; Sutlief S and Wallner K, "Cs-131 Prostate Brachytherapy and Treatment Plan Parameters." Medical Physics, Volume 34, 2007, 2431; Kurtzman S, "Dosimetric Evaluation of Permanent Prostate Brachytherapy Using Cs-131 Sources" International Journal of Radiation Oncology Biology Physics, Volume 66 (Supplement 3), S395).

The monotherapy Cs-131 trial will continue to follow patients with annual updates on symptoms and patient long-term survival data.

Recently accepted for publication was the Cs-131 Advisory Group’s (CAG) article entitled “Recommendations for permanent prostate brachytherapy with 131Cs: a consensus report from the Cesium Advisory Group”. The objective of the article was to provide consensus recommendations for Cs-131 prostate brachytherapy based on experience to date for physicians still unfamiliar with Cs-131. The recommendations are based on three clinical trials, one of which has completed accrual and has been published in the peer reviewed literature, and combined CAG experience of more than 1,200 Cs-131 implants. The recommendations from the group are designed to aid practitioners in the safe and effective delivery of Cs-131 prostate brachytherapy. The Consensus Paper was published in Brachytherapy in the fourth quarter of calendar year 2008. The CAG is sponsored by the Company.

The prospective randomized monotherapy trial headed by Dr. Brian Moran of The Chicago Prostate Cancer Center directly compared Cs-131 to I-125 PSA response and treatment related morbidities following brachytherapy for localized carcinoma of the prostate in low to intermediate risk patients. Dr. Moran concluded that prostate brachytherapy with Cs-131 is effective and well-tolerated; both PSA response and acute morbidity profile are very encouraging. Dr. Moran will continue to track these patients in order to collect long-term outcomes.

Leader in the development of permanent seed brachytherapy in the treatment of cancer.