A new form of chemo-immunotherapy combination works very well — in mice!

Alas, our friends at The Daily Telegraph in the UK seem to have managed to hyperinflate some early scientific findings into an overnight cure for prostate cancer in general and  metastatic, castration-resistant prostate cancer in particular.

So that we can get the facts straight up front, the article in The Daily Telegraph (entitled “Prostate cancer could be ‘wiped out’ by new treatment“) is based on research just published by Shalapour et al. in Nature, and also discussed in a media release issued by the University of California San Diego. What is more, this is all based on research in mice … so we are a long way from knowing how well this might actually work in humans.

What Shalapour and his colleagues have shown is that if one is able to block the development or function of immunosuppressive B cells in mice, or remove them entirely before treating the mice with a low dose of a chemotherapeutic agent known as oxaliplatin, the prostate tumors in the mice were almost completely destroyed by the mice’s own immune system. The team got similar results when low-dose oxaliplatin was combined with a drug known as a checkpoint inhibitor.

Scientifically, this is very interesting. However, to claim that such a therapy may wipe out prostate cancer is a gross exaggeration. Treatment of actual patients with process that can suppress B cells (for example by use of a checkpoint inhibitor) and then treat the prostate cancer tumors with oxaliplatin is certainly theoretically possible. Oxaliplatin (Eloxatin) is a widely available form of chemotherapy, commonly used in the treatment of colon cancer, and the first checkpoint inhibitors have now also reached the market. (Some readers may have heard of drugs like nivolumab [Opdivo] and pembrolizumab [Keytruda] that have already been approved for the treatment of cancer — but not yet in prostate cancer.)

We certainly need to be paying attention to developments in this field, which may hold great potential in the management of late-stage forms of prostate cancer — but treatment with this type of combination therapy comes with considerable risk for very serious side effects, and there is no way in heck that such a therapy could be used to “wipe out” the potential problems associated with early stage prostate cancer.

8 Responses

  1. Are there any data on whether this works on American mice?

  2. The research appears to have been done in San Diego, so I think they must have been American mice.

  3. They may have been Mexican mice that illegally crossed the southern border from Tijuana, although there are some famous mice just north in Orange County as well. Lucky mice — everything seems to cure them.

  4. The B-cells (B-lymphocytes) can be depleted with widely available rituximab (Rituxan) injections. After B-cells are depleted, the low dose of oxaliplatin can be administered. Any patient with late-stage prostate cancer can try this inexpensive treatment.

  5. With respect to Felix’s comment above …

    (1) You do need a qualified and experienced physician (e.g., a medical or hematologic oncologist) to prescribe and oversee treatment with drugs like rituximab and oxaloplatin. (2) This is not a benign treatment regimen. These drugs have significant side effects — see here and here). (3) As far as I am aware, there are no data at all to indicate that this would be effective in man (as opposed to mice). (4) We don’t know what the most appropriate doses of the two drugs might be in men with castration-resistant prostate cancer (CRPC) — metastatic or non-metastatic. (5) There is no reason, at this time, to believe that any health insurance company would necessarily cover the costs of such treatment.

    Having said that, as Felix points out, it is certainly possible to talk to any good medical oncologist about whether he would be willing to try such a therapy in men with CRPC. These drugs could be used off-label as suggested.

  6. Thank you. Now I doubt my approach, because I have read, that “the crucial immunosuppressive B cells are plasmocytes” and that the normal plasmocytes do not express the CD20 protein and therefore can’t be depleted with the rituximab.

  7. I have found a published case study of a patient with advanced prostate cancer who had a 26% PSA reduction after treatment with the rituximab (375 mg/m2 weekly, well tolerated).

  8. Dear Felix:

    While case studies like this are always interesting, I would note that it is actually not that difficult to lower the PSA of a patient (even one with late stage disease) by 25% or so for a period of time using all sorts of differing types of treatment.

    The key question, however, is whether such effects are associated with either an improvement in the patient’s quality of life or an extension of his survival (or ideally both).

    Before we recommend to anyone that they actually try this form of treatment, we are going to need to see some data that actually (at a minimum) suggest one of these outcomes as a consequence of this type of treatment — in man as opposed to in mice.

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