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Paul Sanderson: Immune response

Paul Sanderson
Monday, 30 September, 2013
Paul Sanderson

IMMUNOTHERAPY is often dismissed in cancer even though it has succeeded where other treatment has failed.

Yet, while it is being studied in major cancer centres and universities from the US to the UK, Sweden, Japan, China and Australia, it remains the poor cousin in focus and funding.

Part of the resistance, going back more than a century, rests in misinformation perpetuated about the first modern experiences in immunotherapy. The Pulitzer Prize-winning book The emperor of all maladies, released in 2011 and subtitled “A biography of cancer”, has no listing in its index for “immunotherapy”.

However, early in the book there is this footnote by the author: “In New York in the 1910s, William B. Coley, James Ewing, and Ernest Codman had treated bone sarcomas with a mixture of bacterial toxins — the so-called Coley’s toxin. Coley had observed occasional responses, but the unpredictable responses, likely caused by immune stimulation, never fully captured the attention of oncologists or surgeons.”

Dr William Coley was chief of the bone tumour service at Memorial Hospital, which later became the Memorial Sloan-Kettering Cancer Center. He was also chief surgeon at the Hospital for the Ruptured and Crippled, a lecturer in clinical surgery at Columbia University and professor of clinical surgery at Cornell Medical College. John D Rockefeller Jr made his first donation to cancer research for the development of Coley’s Toxins.

There are four errors in that brief footnote from The emperor of all maladies. The use of “toxin” instead of the accepted “toxins” is negligible; the “1910s” less so. Coley used his immunotherapeutic vaccine across four decades from the 1890s.

Dr James Ewing, who was the medical director of Memorial at the time, was a prominent proponent of radiation. Dr Ernest Codman was a Boston surgeon and also a radiation advocate. Neither of them administered Coley’s Toxins. Both were active opponents of it.

Ewing, perhaps the foremost pathologist of his time, who gave his name to Ewing’s sarcoma, claimed multiple times that his own initial pathological diagnosis must have been incorrect in order to deny cures by Coley. As science writer Stephen Hall relates in his 1997 book A commotion in the blood, it was only in 1934 that Codman, founder of the Registry of Bone Sarcoma, reversed his position and agreed that “miracles have occurred, and in Coley’s own undiscouraged hand these miracles have not been infrequent”.

The reference to “not infrequent” relates to the final error in the footnote of “occasional responses”. In a study of Coley’s Toxins in Cancer Research, 484 representative cases were analysed. Of a total of 312 inoperable cases, there were 190 complete regressions.

This year at Memorial Sloan-Kettering, five adults with acute lymphoblastic leukemia were treated with immunotherapy using genetically modified T cells. The five patients achieved complete remission.

Professor Linda Liau, vice chair of neurosurgery at the University of California, Los Angeles, and editor-in-chief of the Journal of Neuro-Oncology, has, along with colleagues, used immunotherapy since 2003, a dendritic cell vaccine, to treat grade IV glioblastoma patients with increasing success, including patients remaining disease-free for more than 6 years.

In 2005, immunotherapy was used in stage IV pancreatic cancer at Germany’s University of Würzburg. After the 72-year-old patient was weaned from vaccination in a “state of no evidence of disease”, there was recurrence, but it remains a significant breakthrough in a cancer universally described as incurable.

More than 100 years after Coley began his first treatments, a version of his bacteria-based vaccine was used again in 1999 in a regional university hospital in Japan. The 37-year-old patient had an unresectable rectal carcinoma with extensive local spread. The Streptococcus-derived immunotherapeutic agent was injected into the tumour nine times as part of a multidisciplinary approach, and resulted in a complete remission.

With so many decades lost and countless deaths, harm and secondary cancers, to not make a primary shift to immunotherapy now would surely be unconscionable.

 

Paul Sanderson, who has just moved back to Australia from New York, is the author of Briggs: love, cancer, and the medical profession, a book he researched and wrote after his wife died of complications from rectal cancer. His petition — Petition for Briggs for cancer immunotherapy for all — has been signed by doctors at US cancer centres and universities, and by prominent figures in media, film and sports.

Comments

There are two very notable common uses of immune modulation to treat cancer - both of which have been in common, but not common enough, use in Australia for decades.

1. BCG for transitional cell Ca of the bladder

and

2. Imiquimod for basal cell and early squamous skin cancers.

Tragically, our Medicare system encourages surgery first, and conservative (and less remunerative) treatments second.

I read this article anticipating a short review on immunotherapy in cancer, but what I found was something far different that left me wondering what the intent of publishing this article is. Active research into immunotherapy in cancer is ongoing: a simple PubMed search using the keywords "immunotherapy" AND "cancer" returns more than 58000 articles, including more than 3000 in 2012, and approximately 1800 so far in 2013. These numbers that have climbed steadily from approximately 500 in 1981 and do not reveal an area of cancer research that has been neglected.

With this in mind, I looked further into who the author is, and found an actor with a self-published book relating the loss of a loved one and an on-line petition with celebrity endorsement. His story is not unusual, and I trust his motives are sound. Two truths in medicine are that malignancy kills people and that mistakes are made.

What does disturb me though, is that there are now multiple websites proclaiming the publication of an article in the Medical Journal of Australia -- and citing this article -- with the subtext that treatment with undefined bacterial extracts now has acceptance as an alternative to current evidence-based treatments. I am concerned that this perceived endorsement might have the unfortunate flow-on effect of people with malignant disease seeking practitioners -- medical or other -- who are willing to administer these extracts to patients in place of them receiving current best-practice treatment and care. There are already too many charlatans out there dispensing vitamin C infusions, potions and infinitely dilute solutions, without inadvertently adding another way for them to take advantage of people at their most vulnerable.

This article's welcome, needed agendum is stated by the well-versed author in no uncertain terms: to beget a broad-based "primary shift" toward the evidence-based use and development of immunotherapy. As for staying instead with "evidence-based" standard treatment, chemotherapy and radiation do not achieve remissions in over ninety percent of cancers. We've know that for a long time and yet have self-servingly continued to use them. We've also seen patient after patient, and their loved ones, devastated by the side effects and the secondary cancers.

A single google search also reveals that the previous post misrepresents whom Mr. Sanderson is. It's an interesting extension of the scare tactics behind Dr. Coley's work having been so obviously undermined, and it's a pleasure to see a committed, honorable doctor's reputation being restored by him. I applaud MJA InSight for giving him a voice here on behalf of not only cancer patients but oncologists and surgeons who feel pressed into unethical medical procedures by profit-oriented, or willfully blind and resistant, treatment-centre policies regarding the use of chemotherapy and radiation. It's a large part of why there are PubMed articles on immunotherapy going back tens of years while the average cancer patient still has no access to it, and certainly won't usually be informed of its existence. No, this artcle isn't another business-as-usual "short review on immunotherapy in cancer." It's far more urgent than that.

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