THE "NEW" PROSTATE CANCER INFOLINK

We have been kindly advised of the fact that the full text of the Yamamoto et al. paper on treatment of men with prostate cancer with Gc-MAF is available on line on the Translational Oncology web site.

In our prior commentary, based exclusively on the abstract of this paper, we had asked the following questions:

• What was the clinical stage, grade, etc., for the 16 patients at the time of their treatment with Gc-MAF?
• What other treatments (if any) did they have before or after treatment with Gc-MAF?
• When were they actually treated and have other patients been treated subsequently?
• How were they followed up?
• What is meant by the phrase “no recurrence” in the abstract?
• Is a Nagalase level comparable to that of a healthy control in a patient previously diagnosed with prostate cancer actually sufficient evidence that that patient is “tumor-free”?

The full text allows us to answer many (but not all) of these questions.

• The 16 patients were all Japanese men, aged between 46 and 76 years at the time of their initial diagnosis, treated in Japan. However, the dates of treatment are not available.
• At the time of diagnosis, the men’s PSA levels ranged from 2.5 to 68.4 ng/ml.
• Of the 16 men, 9 had received a radical prostatectomy at some time in the past and 12 had received some (unspecified) form of hormone therapy; no patient appears to have received radiation therapy at any time.
• Of the 9 men who received a radical prostatectomy, all 9 achieved a PSA level ≤ 0.3 ng/ml immediately post-surgery and 5/9 achieved a PSA level ≤ 0.1 ng/ml.
• Immediately preceding treatment with Gc-MAF the patients’ PSA levels ranged from 0.09 to 21.7 ng/ml.
• No patient had evident metastatic disease, based on the results of a CT scan immediately prior to Gc-MAF treatment.
• There is no information given regarding the time from initiation of prior therapies to initiation of Gc-MAF treatment.
• Immediately prior to treatment, all 12 patients had serum Gc activity levels ranging from 16.9 to 77.8 percent of the average serum Gc level of a group of seven healthy controls.
• Furthermore, the lower a patient’s pre-treatment serum Gc level, the higher his Nagalase level.

As previously discussed, all patients were treated once weekly with 100 ng/ml of Gc-MAF for a period ranging from 14 to 25 weeks. Results following that treatment can now be fully summarized as follows:

• There was a clear, linear correlation between serum Gc activity and Nagalase activity over time; the Nagalase activity fell as MAF precursor activity rose.
• All 16 men had their Nagalase activities reduced to that of a normal healthy control by the time that Gc-MAF therapy was stopped.
• In 7 years of follow-up, no patient showed a recurrence of elevated Nagalase activity.
• In 7 years of follow-up, no patient showed any sign of metastatic disease on a CT scan
• No information is provided about the PSA levels of the patients over the 7 years of follow up (which is perhaps unfortunate).
• In men who had received a prior radical prostatectomy, there was a clear correlation between declining Nagalase activity and declining PSA levels over the course of treatment. However, in the men who had not received a radical prostatectomy, while Nagalase activity fell, the PSA level remained stable.
• No information is provided about the overall survival of these 16 men since the initiation of treatment.

What is one to make of this paper?

Well in the first place it would be naive to not to take it seriously. Something is clearly happening! And if at least one drug company doesn’t pick up on this research, I would be disappointed (but then that wouldn’t be the first time!) Secondly, it seems likely to me that some of the data not provided in this paper is available somewhere. We still don’t know, for example:

• The clinical stages of the patients at diagnosis
• The form(s) of hormone therapy given
• Whether the men who had had or were receiving hormone therapy continued on hormone therapy after Gc-MAF treatment
• The patients’ post-treatment PSA levels over time
• The patients’ long-term outcomes over time

We are then faced with the question “What is a cure?” If these 16 men all really had stable disease for a minimum of 7 years, with no progression, and no other therapy following 14-25 weeks of Gc-MAF treatment, that certainly sounds like a remarkable outcome to me!

One last thing, just so that it is absolutely clear. Gc-MAF is not patient specific. In other words (unlike biologics like sipuleucel-T), it does not have to be extracted from the serum or tissues of the individual patient. In this trial, the serum required to make the Gc-MAF used to treat the patients was simply donated by members of the staff of the Socrates Institute.

Filed under: Drugs in development | Tagged: Gc-MAF |