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Total Therapy – Day Two

Posted on October 07 2009 by Pat Killingsworth | 924 views

Nick has generously agreed to help educate us about Total Therapy. This is a new concept for me, but I know some of you are familiar with this treatment philosophy. Nick wrote this yesterday:

As for getting primed about Total Therapy, I would refer you via google to a powerpoint presentation called “The Myth of Incurability.” If you google this and Barlogie, it will come up. That has a (fairly technical) history of the program, how is has evolved over time, and the data that supports it.

Some highlights for you before reading the report:

* Total Therapy for Myeloma evolved from the therapies developed over a period of 40 years for Childhood Leukemia, which is now cured in about 90% of the cases. The essence of Total Therapy was to use all available medicine all at once in newly diagnosed patients, rather than using the minimal amount required to achieve a response, waiting until drug resistance happens, and switching up drugs.

* There have been four Total Therapy programs since Bart set up shop in 1989. The first program used neither Thalidomide nor Velcade. Total Therapy 2 tested Thalidomide. Total Therapy 3 included Velcade. Total Therapy 4 is now testing a “lite” arm (which I had) versus a “standard” arm to determine whether the same results can be achieved with less poison.

* Total Therapy consists, broadly speaking, of four phases.

– Induction (drugs are used to suppress the cancer)
– Transplants (two consecutive auto transplants, with thalidomide and dex taken after each)
– Consolidation (induction drugs used to further kill cancer)
– Maintenance (three years of meds)

* Induction consists of a small dose of Melphalan (mostly just to observe the reaction to the drug, which allows them to tailor treatment), plus Velcade, Thalidomide, Dex, and then four types of old-school chemotherapy: Cisplatin, Adriamycin, Cyclophosphomide and Etoposide. In the “standard” arm there are two cycles, one month apart. In the “lite” arm there is one cycle.

* Transplants are high-dose Melphalan, and Velcade, Thalidomide and Dex are taken concurrently for synergistic effect. The “standard” arm uses the usual 200mg/m2 of Melphalan over a one or two-day period; the “lite” arm splits it over four days.

* Consolidation consists of slightly dose-reduced induction (the same drugs except for the Melphalan). The “standard” arm uses two cycles; the “lite” arm uses one cycle.

* Maintenance consists of three years of weekly Velcade and Dex, plus Revlimid days 1-21 of each 28 day cycle.

* “Mainline” therapy, when it uses a transplant, does so to “lock in gains” achieved from induction. Total Therapy, on the other hand, uses the transplant as an active part of therapy. Instead of waiting for 6-12 months to achieve remission and then transplanting, the transplants are much quicker. I did not achieve complete remission until after consolidation — although the results of the transplants were probably still being seen. Less aggressive doctors wait for 100 days post-tranplant to assess its effectiveness. By the time 100 days had come and gone, I’d already gone through a second transplant and consolidation therapy.

* The theory, essentially, is that by cutting off every pathway that the myeloma cells have to escape, they are all killed. In contrast to a more measured approach where the myeloma develops drug resistance and eventually nothing works any longer.

* An important part of Total Therapy is the use of a detail analysis of genes (they now use an 80-gene test) from bone marrow to determine the precise type and subtype of myeloma — they have something like 20 different varieties and this type of detail is far more useful than potential Chromosome 13 deletion, etc. (which Bart has ceased to use as an indicating factor for more than three years now since it no longer has a bearing on outcome). The initial gene array determines whether one has “high risk” or “low risk” disease. Low risk disease comprises about 85% of cases, and the cure rate for these people is quite high. High risk disease is a different animal — tougher to treat and dire outcomes.

NOW you are ready to read the presentation. 🙂 You will note that there are people 20 years out that have remained in remission; there are a sizable percentage of people 10 years out that benefitted from Thalidomide; the cure fraction for low-risk patients in Total Therapy 3 is expected to be 70%+. When you read these charts, bear in mind that Event Free Survival (and other data) INCLUDE people that have died from other causes, so the cure rate is conservative.

Wow! That’s a lot of information to digest. I know it is working for Nick. Not so well for some others. I will comment on Nick’s explanation, along with the pro’s and con’s of this therapy approach tomorrow.
In the meantime, feel good and keep smiling! Pat

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