Re: What are my options? - Leigh

[Guest guest]

Hi ,

Depending on the nature and severity of your side effects from Gleevec (IM) and

Sprycel,

you and your consultant might consider trying a drug approach called " pulse

therapy, "

rather than moving to something so radical as BMT. With a 4-log reduction, your

disease is

at low risk of progressing as long as you are able to tolerate either drug for

periods as

short as a month, followed by a break. If, on the other hand, your side effects

are

intolerable after only a week or two of IM or dasatinib therapy, then what I

write below will

probably be of no use to you.

Pulse therapy - that is, intermittent rather than continuous use of a drug - is

employed to

good effect with many kinds of cancer chemotherapy in order to decrease side

effects,

and in a number of infectious diseases (which in many respects CML resembles

more than

it does a cancer) in order to increase the effectiveness of treatment. It is

absolutely NOT a

standard approach to the kinase inhibitors (IM and dasatanib), but several

people,

including myself, have used it for long periods of time to good effect, and

there is

increasing interest in it as a possible alternative to continuous drug therapy.

A trial of

Gleevec pulse therapy is about to get underway in Australia, I understand.

As I've written on this list previously, I have cycled on and off IM for nearly

5 years. Until

recently my schedule was two months on, one month off, two months on, two months

off,

etc. For the most recent two cycles I have remained off for 6 weeks at a time,

then back

on for two months. If I continue to do well with this I will switch sometime in

the next

couple of years to 6 weeks on, 6 weeks off - where I'll stay until a cure for

CML is found!

I began doing this (against the advice of my physician, I should tell you) in

order to regain

my pre-CML quality of life (even though my side effects weren't that severe, I

didn't like

the perpetual fatigue and mental fuzziness, plus a couple of other nuisance

symptoms

such as hoarseness and diarrhea); to avoid as-yet-unknown but potentially

dangerous

adverse effects which struck me nearly inevitable with so powerful a drug used

continuously over many years; and hopefully to increase the effectiveness of my

therapy.

It worked great on the side effects: since the worst of them take about a month

to come

on once I start IM, and only about a week to wear off once I stop, I only

experience about 5

weeks of side effects out of every three months.

There's no way of knowing whether the pulse regimen is helping against long

term-

adverse effects, but the scare earlier this year concening a possible increase

in heart

failure among patients on IM strengthened my resolve on this point - whether

this

particular problem turns out to be real or not.

As to improving efficacy of treatment, there's no way of knowing from my

personal sample

of one, but I can tell you that since I started pulse therapy almost five years

ago, I have

gone from an initial 4-log reduction to PCRU (PCR undetectable - now called CMR,

or a

complete molecular response). Whether or not I can attribute this success to

pulse therapy,

it obviously hasn't hurt me either.

The principle reason I believe pulse therapy may increase efficacy is this: it

has been well

established that continuous administration of IM (and probably dasatanib, too)

actually

drives CML stem cells into quiescence (non-dividing, that is), a state in which

they are

insensitive to the drug. By stopping the drug for longish periods of time (just

a few days

isn't enough, it's known from studies of these quiescent cells in vitro) the

impetus to

remain quiescent is removed. Each time that happens it just may be that a few of

the cells

start cycling again - thus rendering them susceptible to IM's killing effect

once it is

restarted. By repeating this again and again over time I hope to decrease the

pool of CML

stem cells - maybe even to zero! Conversely though, uninterrupted exposure of

these cells

to a drug which does NOT kill them, may in time lead to active resistance - and

that is

something I would like to avoid.

While I'm happy to be my own guinnea pig, I do not recommend this highly

non-standard

therapy to just anyone; however, because standard therapy no longer seems to be

an

option for you, - AND because BMT even from a matched related donor is an

uncomfortable and risky business - consideration of a non-standard drug approach

seems

quite reasonable to me.

I'll be happy to discuss this further with you or your physician, if he or she

is interested.

Regards,

R, MD

>

> Hi ne

>

> I was very interested to hear your story.

>

> I have had very similar problems. I was told on Friday that I have

> reached the end of the road with the dasatanib ( after being on a r much

> reduced dosage ). I, too, have had a 4 log reduction.

> I have had a lot of side effects with both the glivec and dasatinib,

> many of which are not in the 'book'.

>

> We talked about interferon but my consultant here in London, was not

> keen.

>

> I will probably try and see if I can get AMN, although it is fairly

> unlikely to suit me side effects wise.

> After that it is the BMT. I do have a related donor which makes things a

> little better.

>

> Not easy, so many people seem to tolerate the BMS very well. My

> consultant suggested that the side effect profile of BMS is worse than

> that of glivec. I had thought it was the other way round.

>

> I hope that interferon does it for you. Let me know how it goes

> Regards

>

>

> London, England

>