Intralesional therapy for melanoma, PV-10, and Provectus. Now there's a mashup!

Intralesional melanoma therapy (A procedure in which the "treatment" is directly injected into superficial tumors and in theory, not only does that tumor die, but "by stander" tumors at more distant sites die too!!!) was first recorded back in 1975.  A 75 year old male with 64 melanoma mets just below the skin, as well as junk in his lungs, had 17 superficial lesions injected with Bacille Calmette-Guerin over a period of 8 months. (BCG is a vaccine against some strains of tuberculosis, but does contain a weakened version of the bacteria itself within it.) In the end, all 17 tumors injected resolved and his pulmonary mets diminished by more than 50%!  However, enthusiasm for BCG as a melanoma treatment waned as patients in subsequent trials experienced anaphylactic reactions and death due to disseminated BCG, and randomized trials failed to replicate significant clinical benefit.

Later, intralesional therapy was tried using all sorts of things.  More recently Allovectin-7, OncoVEX, and PV-10 have demonstrated positive results, killing melanoma at the injected site and systemically.

Allovectin-7, is a soup of DNA, that attempts to change the gene make-up of tumor cells. In a study reported in 2012, it provided a 12% overall response rate with no grade 3 or higher toxicities in patients with stage III/IV melanoma with injectable cutaneous lesions.

OncoVEX is a 2nd generation herpes virus embedded with GM-CSF...a substance that causes the body to make more white cells. (GM-CSF can be given to premature babies and leukemia patients with low white cell counts to help build them back up....and reverse immune suppression.) But, in OncoVEX, it is thought to only replicate in the tumor cells.  The white cells produced in the process kill off the tumor cells.  In a phase 2 trial reported in 2012, 20% of patients achieved a complete response and 28% gained an overall response.  92% of the responses were durable to at least 6 months, and the majority were ongoing with a range of 18-40 months.  Responses were found in patients with all stages and systemic tumors were eradicated in some patients.

Rose Bengal was first utilized in the 1800's to dye fabrics and color the feet of Bengali women red for weddings and celebrations. Later it was used as a staining agent to find corneal lesions and then as an IV preparation to check for impaired liver function.  The "Aha!" moment came in the 1980's when Japanese tests of a "food dye" to determine tumor origin, found dose-dependent survival increases. After a few other sundry studies....PV-10 was born.  It is a 10% Rose Bengal solution, with a 30-minute half-life, excreted via bile. PV-10 is excluded from normal cells, but slips through the cell membrane of cancer cells (liver, breast, melanoma, and others) because their cell walls have a higher lipid content. Once inside, PV-10 triggers lysosomal release (the part of the cell that digests waste), killing the cell in 30-60 minutes. Antigenic tumor fragments are believed to produce the 'bystander effect' leading to immediate reduction in tumor burden and concomitant immunologic activation.

(See blog posts on 10/12/2012 and 12/14/2013 for particulars on Rose Bengal studies.)

Results from a study with Rose Bengal, published in 2012 by Agarwala:  Objective response was achieved in 51% of target lesions (25% complete response and 26% partial response).  Furthermore, disease control (combined Complete, Partial, and Stable responses) was achieved in 69% of lesions.  In bystander lesions: 33% = objective response and 50% achieved disease control in these lesions.

Now....I don't know if any of these treatments will live up to their initial studies or hype!!!  I'd like to think they would because of the people they could help.  I have high hopes for PV-10 in particular because it is so cheap, has so few side effects, and is doing rather well...so far.  The big dogs at Moffitt seem to find it promising, too, and have started a study (enrolling now) to examine what injections of PV-10 does for melanoma patients and their tumors as well as the immunologic agents that start floating around in their blood after its use.  However....

Provectus (the company making PV-10) would like to have you think that, as well.  They have been very big on touting their new Moffitt connection! (Blogger dude [see reference below] even quotes Dr. Weber.  Wonder if The Wizard Weber knows that??!!!) But, for very different reasons...their stock price being foremost.  Per their premier blogger..."It costs very little to manufacture PV-10." (No Shit Sherlock...poor women used to dye their feet in it!!!) Yet, Provectus gurus predict a $20,000 - $30,000 treatment price...assuming several cycles using 1-2 vials per cycle at a cost of $5,000 per single use vial!  "At these prices, however, PV-10's gross margin would be more than 80%.  If (THEIR TYPO NOT MINE!) would be in excess of 99% should a sales return-type allowance not be included."

Seriously????  No final data in.  Touting their stock price rise after the trial began at Moffitt. And then, as an aside to their investors..."Hey, boys and girls!!!  We can make you a 99% return on your investment on these sad schmucks, with all their cancer, and this cheap ass shit!!!!"

And you thought.... "Man, I've got cancer.  What the hell?  I'll just take the best medicine I can find, damn the side effects."  Sadly...Big Pharma Provectus thought..."Desperate Bastards!  Look at 'em.  This shit is super cheap!  They are used to paying out the ass for ipi.  Lord only knows what they'll end up paying for anti-PD1!  We can make a fortune!"

Check it Mr. Provectus Blog Man.  We don't all roll over for you. - c

By the way....had I purchased stock in Provectus in November 2013, by the end of December, I would have quadrupled my investment!  You heard it here first.  I feel sorry for all those patients on the boards looking to these factors as indicators as to when drugs like Nivolumab and others will be hitting the market.  Sadly, these folks are not about "us".  They are about their companies, pleasing their investors, and making big bucks.  They don't care if they make it off of hype or real success in cancer treatment.  It is all the same to them.- c

References:
1.  Intralesional Therapy for Metastatic Melanoma. Sanjiv Agarwala, MD, The Melanoma Letter, 2012.
2.  Connecting the dots...Provectus Pharmaceuticals. Sept 30, 2013...A blog by "the author" with a complicated investment disclaimer but with admittedly HUGE investments in Provectus!!!