Tookad-Soluble + VTP effective and safe in treatment of low-risk prostate cancer

Another new media report (based on data just published in Lancet Oncology) states that “vascular-targeted photodynamic therapy” or VTP in combination with an experimental drug called padeliporfin or WST11 can be used to successfully treat low-risk prostate cancer.

Now this is going to become a controversial issue, because there are going to be very real questions about the need for such treatment in large numbers of patients with low-risk disease in the first place (because all such patients are potential candidates for active surveillance as opposed to immediate treatment). The cost of such treatment will clearly also become a factor if the associated new drug gets approved for this use. As will become evident below, the results are fascinating, but they don’t show anything close to 100 percent elimination of cancer.

The abstract of the paper by Azzouzi et al. is available on line; an editorial by Freedland is also published in Lancet Oncology (but only part of the first paragraph is available to non-subscribers); there is a media release on line from the University College of London Hospitals (UCLH); and there is already commentary on this new paper available on the CNBC web site.

According to the abstract of the original article (along with information about the trial on the web site), the investigators, with funding from the developer of padeliporfin (also known as TOOKAD-Soluble), conducted a randomized, controlled trial in > 400 patients at 47 different academic and community-based prostate cancer treatment centers in Europe. Between March 8, 2011, and April 30, 2013, the trial enrolled men with low-risk, localized prostate cancer who had received no prior treatment and whose Gleason score was no higher than 3 + 3 = 6. These men were then randomized to one or other of two forms of management:

  • Active surveillance based on best clinical practice at the time  of the trial (i.e., biopsies at 12-month intervals; PDSA tests and rectal exams at 3-month intervals)
  • VTP using an intravenous injection of padeliporfin (4 mg/kg) over 10 min; optical fibers inserted into the prostate to cover the desired treatment zone; and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s

The trial had two co-primary endpoints:

  • Treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months of follow-up)
  • Absence of definite cancer (absence of any histology result definitely positive for cancer at month 24).

Here are the core results reported by Azzouzi et al.:

  • The trial enrolled 413 eligible patients.
    • 206 patients were randomized to VTP
    • 207 patients were randomized to active surveillance
  • Average (median) follow-up was 24 months.
  • Disease progression at month 24 was observed in
    • 58/206 men treated with VTP (28 percent)
    • 120/207 men managed on active surveillance (58 percent)
  • Absence of definite cancer (as defined above) at 24 months was observed in
    • 101/206 men treated with VTP (49 percent)
    • 28/207 men managed on active surveillance (14 percent)
  • VTP was described as “well tolerated”.
  • The most common grade 3 or grade 4 adverse events were
    • Prostatitis
      • 3/206 cases in the VTP group (2 percent)
      • 1/207 cases in the active surveillance group (< 1 percent)
    • Acute urinary retention
      • 3/206 cases in the VTP group (2 percent)
      • 1/207 cases in the active surveillance group (< 1 percent)
    • Erectile dysfunction
      • 2/206 cases in the VTP group (1 percent)
      • 3/207 cases in the active surveillance group (1 percent)
  • The most common serious adverse event in the VTP group was retention of urine (in 15/206 patients) but this event resolved within 2 months in all patients.
  • The most common serious adverse event in the active surveillance group was myocardial infarction (in 3/207 patients).

The authors interpret these results by concluding that

Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy.

However, the principal investigator and senior author of the study, Dr. Mark Emberton, is rather more enthusiastic in the media release from UCLH:

These results are excellent news for men with early localised prostate cancer, offering a treatment that can kill cancer without removing or destroying the prostate.

This is truly a huge leap forward for prostate cancer treatment, which has previously lagged decades behind other solid cancers such as breast cancer. In 1975 almost everyone with breast cancer was given a radical mastectomy, but since then treatments have steady improved and we now rarely need to remove the whole breast. In prostate cancer we are still commonly removing or irradiating the whole prostate, so the success of this new tissue-preserving treatment is welcome news indeed.

Apparently, again according to the media release from UCLH,

In the trial, only 6 percent of patients treated with VTP needed radical therapy compared with 30 percent of patients in the control arm who were under active surveillance. The chances of cancer progressing to a more dangerous stage were three times lower for patients on VTP, and the treatment doubled the average time to progression from 14 months to 28 months.

We understand that the effectiveness and safety of VTP using Tookad-Soluble is now under review by the European Medicines Agency and so it could be approved in Europe as early as next year. Whether these data would be sufficient to permit approval of this technique here in the USA is a harder question to answer.

The “New “Prostate Cancer InfoLink sees this development as being very interesting indeed, but we would caution readers that the data are based on just 2 years of follow-up and that there have to be real questions about which men who have the option of considering active surveillance might still be well served by such a form of care as compared to having immediate therapy of this type.

We also note that Dr. Emberton is a member of the Scientific Advisory Board of The “New” Prostate Cancer InfoLink.

7 Responses

  1. Sitemaster, you are guilty of being logical.

    3 cardiac events in the AS group; I am assuming these were in the “get it out of me, do something, anything anxiety group.” Were probably poorly chosen as AS candidates. Stress reduction is a medical benefit. Not saying treatment is the proper way to reduce stress, for those three (and other less drastic cases) it would have been well worth it.

  2. Michael:

    And you are guilty of making assumptions. People have cardiac events all the time — for all sorts of reasons. I had one. And it had nothing to do with stress at all. :O)

  3. I don’t understand Emberton’s enthusiasm for a treatment that leaves half the cancer inside, and 28% of the cancers had already progressed within 2 years.

    I’d also point out that the progression stats here in the active surveillance cohort are disappointing. In Klotz’s active surveillance trial, only 25% had progression that required treatment by 5 years, whereas here, 58% required treatment by 2 years.

  4. Dear Allen:

    That’s one of the several reasons why I am not exactly “bowled over” by these data. However, I am not sure where you are getting the data that suggests that this is a “treatment that leaves half the cancer inside”. Like every other treatment I am aware of, there is a subset of patients that progress after treatment. The problem I am having is that the abstract doesn’t tell us exactly how the patients were selected for entry into this trial. Did all the patients have an mpMRI-guided or an MRI/TRUS fusion-guided re-biopsy prior to being considered eligible for active surveillance. It appears that they didn’t. Did they even have a repeat biopsy after the initial decision to consider them appropriate candidates for active surveillance. That is unclear.

    On the other hand, if one could pick the best candidates for this type of therapy and use it effectively to treat younger men who would otherwise need to be on AS for the next 30+ years, then I can see how it might be a very attractive form of treatment for some men with low-risk disease.

    As always, the proof of the pudding tends to be in the accuracy with which one can pick the appropriate patients for treatment.

  5. What I meant by “leaving half the cancer inside” was that 49% had an “absence of definite cancer,” so definite cancer was still present in the remaining 51% after focal ablation. I scratched my head over the AS selection criteria and protocol they used too. Since they were randomized to focal therapy or AS, I assume that the “low risk” patients also only had one or two foci of cancer, unilaterally. And I think you make a good point that we hope it was detected and confirmed on a f/u mpMRI-targeted biopsy, as we know they must have used in the focal ablation cohort.

  6. Sitemaster,

    “guilty of being logical” was by no means intended as offensive. I wish I could consistently claim the title.

    “Now this is going to become a controversial issue, because there are going to be very real questions about the need for such treatment in large numbers of patients with low-risk disease in the first place (because all such patients are potential candidates for active surveillance as opposed to immediate treatment).”

    Unneeded treatment does occur and will continue to occur. Which is preferable, surgery or a drug? Time will tell about this drug.

    Three cardiac events do not a proof make, never claimed they did. Is cancer a stress, untreated cancer a bigger stress for some than others? Is stress unhealthy?

    I think the links are well established if not proven.

  7. Michael:

    I was in no way offended. My point was only that three cases of cardiovascular disorders in the patients on active surveillance could easily have occurred without there being any direct relationship to the patients’ cancers. Let’s start with the simplest: bad diet and lack of exercise.

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