THE "NEW" PROSTATE CANCER INFOLINK

Today’s news deals with such items as:

• Toxicities associated with hypofractionated, intensity-modulated radiation therapy
• Incidental prostate cancer in male patients undergoing radical cystoprostatectomy for treatment of bladder cancer
• A Spanish review of photodynamic therapy
• A proposed mechanism of action for the investigational drug Apoptone™ (HE3235)

Defining the appropriate dose of radiation to treat localized prostate cancer remains a problem. Increasing the dose of radiation (dose escalation) is known to improve biological control of prostate cancer, but is associated with a significant increase in late toxicity. It is believed that the use of hypofractionated, intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs, and Coote et al. have now reported on late toxicity data of a hypofractionated IMRT regime. In this study, eligible men had T2-3N0M0 adenocarcinoma prostate, and either a Gleason score of ≥ 7 or a PSA level of 20-50 ng/ml. All patients received 57-60 Gy to the prostate in 19-20 fractions using five-field IMRT. All patients also received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy. At that time, there was a 4 percent incidence of Grade 2 bowel and a 4.25 percent incidence of Grade 2 bladder toxicity; there was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity; patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. Coote et al. conclude that, “hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment.” However, The “New” Prostate Cancer InfoLink notes that significantly higher doses of radiotherapy are in use in the USA today (up to as high as 75 Gy).

The occurrence of incidental prostate cancer in men undergoing radical cystoprostatectomy (complete surgical removal of the baldder and the prostate) as a treatment for bladder cancer is well established. Mazzucchelli et al. examined whole-mount prostate sections of 248 totally embedded and consecutively examined radical cystoprostatectomy specimens to determine the incidence and features of incidentally detected prostate cancer. Prostate cancer was present in 123/248 specimens (49.6 percent) . Features were as follows: acinar adenocarcinoma, 123/123 (100.0 percent); peripheral zone location, 98/123 (79.7 percent); pT2a, 96/123 (78.0 percent); pT2b, 11/123 (8.9 percent); pT2c, 9/123 (7.3 percent); pT3a, 5/123 (4.1 percent); pT3b, 2/123 (1.6 percent); Gleason score ≤ 6, 107/123 (87.0 percent); negative margins, 119/123 (96.7 percent); pN0 for prostate cancer, 123/123 (100.0 percent); and tumor volume < 0.5 cm³, 116/123 (94.3 percent). Of the 123 incidentally detected cases of prostate cancer, 100 (81.3 percent) were considered clinically insignificant.

González-Peramato et al. have published a review in Spanish regarding evolving data on the potential of photodynamic therapy in a variety of possible clinical indications, including prostate cancer. We have previously referred to the potential of this technique in commenting on a review of evolving therapies by Marberger et al., where we referred to this technique as vascular-targeted photodynamic therapy (VTFT).

Finally, Hollis-Eden Pharmaceuticals has issued a media release about the mechanism of action of Apoptone (HE3235), an investigational agent in clinical trials for the treatment of hormone-refractory prostate cancer. We have previously provided information about the ongoing Phase I/II clinical trial of Apoptone in very late stage disease.