Re: Fw: New radiation therapy offers promising results at VUMC

[Guest guest]

Kaye,

Thanks for posting! The radioactive microspheres do sound

interesting - the sirtex website has more info and references

http://www.sirtex.com/

Clinical Trial results

http://www.sirtex.com/?p=57

References

http://www.sirtex.com/?p=234

The number of patients treated in the trial they highlight

http://www.sirtex.com/?p=57 is kinda small - website refers to " 74

patients (half treated with SIR-Spheres) " in a Phase III trial.

Phase IIIs are usually considerably larger than this, with maybe

several hundred patients minimum. I also noticed they gave the

SIRsphere treatment WITH HAI (hepatic arterial infusion), don't know

if this contributes significantly to good reported time to

progression stats or not.

One thing conspicuous in its absence in the stack of " efficacy

endpoints " (CEA, tumor size, remission length, etc) is the MEDIAN

SURVIVAL TIME. Survival is ALWAYS the primary endpoint in cancer

trials, so I really wonder what is going on that no median times were

given !!! All thats said is there is roughly a 10% difference in two

and three year survival between the therapy groups, notice there are

NO P VALUES ASSOCIATED WITH THIS DIFFERENCE, so it must not have been

statistically significant. Every other parameter in the list has

statistically significant p-value except these! There well may be a

difference - but this trial is too small to detect it!

Because of the small number of patients in the trials, side effect

profile may not be well developed. For example see

http://www.sirtex.com/?p=69 , note they refer to " microspheres have

lodged in a site such as the pancreas " (or elsewhere - this is what

happened to 's Mom).

I guess the major question in my mind is, what situations are these

microspheres best used in? I know that if surgery is POSSIBLE, you

would probably still want to go that route as currently the

data says this is the best chance for " cure " or long term survival.

If you have a few isolated liver tumors, RFA is a good, easy option

for many patients when surgery is not possible. Perhaps microspheres

would be best suited for patients with many small, unresectable,

unablatable tumors in the liver (?)

Whatever the case, I think it is very encouraging to see new stuff

like this coming along!

I saw a recent announcement about SIRspheres and Vanderbilt here

http://www.sciencedaily.com/releases/2002/11/021112075901.htm

and here is an abstract with I assume the latest clinical trial

results from the 2002 ASCO meeting (I know this is hard to read so I

tried to interpret following the text!)

**********************************************************************

ASCO 2002 Abstract

Year: 2002 Printable Version

Abstract No: 599 Category: Hepatobiliary Cancer

Author(s): Bruce Gray, Guy van Hazel, , Price,

Moroz, Geoff Bower, Blackwell, Val Gebski, Mount

Hospital, West Perth, Australia; Greenslopes Hospital, Brisbane,

Australia; NHMRC Clinical Trials Centre, Sydney, Australia.

Abstract: Selective Internal Radiation Therapy (SIRT) with SIR-

Spheres® is a new technique for selectively targeting high doses

of radiation to liver tumours. This trial compared the response rate,

time to progressive disease(TPP) and toxicity of a regimen of

systemic fluorouracil/leucovorin(5FU/LV) chemotherapy versus the same

chemotherapy plus a single administration of SIR-Spheres® in

patients(pts) with advanced colorectal liver metastases. The trial

had a run in phase II component and was to continue as a large phase

III but was closed after the Salz data was published so that a new

trial with a Salz control arm could be commenced.

Methods: Twenty-one pts with previously untreated advanced colorectal

liver metastases, with or without extrahepatic metastases, were

randomised into the study. Pts were treated with the 5FU 425 mg/m2

and LV 20 mg/m2 for 5 days q 28 days until progression with or

without SIR-Spheres® during the 2nd cycle of chemotherapy. CT scans

were repeated every 3 cycles and one month after a PR.

Results: Using RECIST criteria, the response rate for eleven pts

receiving the combination treatment was significantly greater than

for ten pts receiving chemotherapy alone (First Integrated Response;

10PR, 1SD versus 0PR, 6SD, 4PD,(95% CI 0.56 -0.99, p<0.001) and Best

Confirmed Response; 8PR, 3SD versus 0PR, 6SD, 4PD(95% CI 0.36-0.97,

p<0.001). The TPP was also greater for pts receiving the combination

treatment (median 15.6 versus 3.4 months, p< 0.001). The number of

pts experiencing Grade 3 and 4 toxicity events was greater in pts

receiving the combination treatment (13 vs 6). There was no

difference in quality-of-life while pts were on treatment when rated

by pts or physicians (p>0.95).

Conclusion: This small phase II randomised trial demonstrated that

the addition of a single administration of SIR-Spheres® to a regimen

of systemic fluorouracil/leucovorin chemotherapy greatly increased

both treatment related response and time to progressive disease with

acceptable toxicity. This treatment combination is now the subject of

further trials to evaluate survival benefit.

**********************************************************************

INTERPRETATION WARNING: I am not a doctor, I have no medical

training, I could be incorrect in the following!

<<Twenty-one pts with previously untreated advanced colorectal

liver metastases, with or without extrahepatic metastases, were

randomised into the study.>>

[KEITH'S NOTE: This was an extremely small trial with only 21

patients - makes me think trialwise SIR Sphere is not " well

developed " , i.e. I would have expected a larger trial than this for

an ASCO presentation. Trial details - Patient population is

previously untreated stage IV colorectal cancer. Note previously

untreated patients ALWAYS have the best response rates, which is why

pharmaceutical companies are so eager to get them into trials!

Anyway, 10 patients got 5FU/LV alone, and 11 got 5FU/LV + SIR

Spheres. The trial was started before Camptosar became " standard of

care " for stage IV, as there was no Camptosar arm in this one they

regrouped and started over adding it in and I guess thats why

there are so few patients reported on here]

<<the response rate for eleven pts receiving the combination

treatment was significantly greater than for ten pts receiving

chemotherapy alone (First Integrated Response; 10PR, 1SD versus 0PR,

6SD, 4PD,(95% CI 0.56 -0.99, p<0.001)>>

[KEITH'S NOTE: " First Integrated Response " must mean what happened

on the first scan where they noticed a response. That's not

necessarily the BEST response because tumors may keep shrinking. " PR "

means " partial response " - tumor shrinks by at least 50%, SD " stable

disease " - no shrinkage but no growth either, PD " progressive

disease " - tumor increased in size. Looks like almost all patients

experienced a partial response in the SIR sphere group versus NONE in

the 5-FU/LV group. p<.001 means these differences are highly

statistically significant, i.e. did not occur by chance. ]

<<Best Confirmed Response; 8PR, 3SD versus 0PR, 6SD, 4PD(95% CI 0.36-

0.97, p<0.001)>>

[KEITH'S NOTE: " Best Confirmed Response " must be best response

observed at any time during the trial. Zero partial responses is not

unusual for 5-FU/LV as it is a not a very effective chemo! That's

why they REALLY needed a Camptosar arm because Camptosar can actually

achieve responses 5FU cannot!]

<<The TPP was also greater for pts receiving the combination

treatment (median 15.6 versus 3.4 months, p< 0.001).>>

[KEITH'S NOTE: TTP means " time to progression " - time from treatment

to when the tumors start growing again. A big difference and again

highly statistically significant at p<.001. Again, notice no info is

given about SURVIVAL TIME, so the better TTP must not have translated

into better survival (again, SIR sphere may result in improved

survival, but there are too few patients in this trial to tell) ]

<<The number of pts experiencing Grade 3 and 4 toxicity events was

greater in pts receiving the combination treatment (13 vs 6).>>

[KEITH'S NOTE: Grade 3/4 adverse events are the more " serious " ones,

may require hospitialization, etc]

There was no difference in quality-of-life while pts were on

treatment when rated by pts or physicians (p>0.95).

[KEITH'S NOTE: I guess that means they gave patients a questionnare

asking about QOL and the two treatments came out about the same in

the their eyes. However, with only 10 patients per group, I

seriously doubt that is anywhere near enough to statistically detect

differences even if such exist!]

Conclusion: This small phase II randomised trial demonstrated that

the addition of a single administration of SIR-Spheres® to a

regimen of systemic fluorouracil/leucovorin chemotherapy greatly

increased both treatment related response and time to progressive

disease with acceptable toxicity. This treatment combination is now

the subject of further trials to evaluate survival benefit.

[KEITH'S NOTE: Given the ineffectiveness of 5FU/LV, they should have

run an arm with SIR Sphere alone to see if adding the 5FU really adds

anything to its efficacy. The chemo was probably the major source of

toxicity in BOTH arms of the trial, so this would be very useful info

to know.]

Anyway, just some thoughts! Microspheres look very interesting to

me. Thanks again for posting Kaye, and hope all goes well with the

PET results!

Best Wishes,

>

>

> -- New radiation therapy offers promising results at VUMC

>

> I HAD PET SCAN THIS AM...WILL KNOW RESULTS TOMORROW AFTERNOON...THE

> FOLLOWING OPTION MIGHT BE OFFERED TO ME..IT IS ACCORDING TO THE

PET...THEY

> ARE REALLY EXCITED ABOUT HOW THIS IS WORKING....I WAS THE PATIENT

THAT ALL

> THE LIVER AND ONLCOLIGIST HAD A CONFERENCE ON THIS MORNING...THIS

SOUNDS

> BETTER THAN SURGERY AGAIN..BUT HAVE TO WAIT TO FIND OUT...THEY SAY

MINE IS

> EARLY AGAIN..THANKS TO A GOOD ONCOLOGIST STAYING ON TOP OF

THINGS !!!! IT

> IS THE LIVER AGAIN...WILL UPDATE YOU AS SOON AS I KNOW SOMETHIN...I

KNEW I

> COULD NOT PUT THIS ON THE LIST BUT WANT YOU AND PATI AND SOME TO

KNOW..THIS

> SOUNDS ENCOURAGING FOR SOME OF US..AND THE DRS. ARE SOUNDING REALLY

THRILLED

> AND HAPPY..THINK IT IS A MAJOR THING...CHAT LATER..HUGS,KAYE

>

>

>

>

[Guest guest]

thanks, need all the info we can get...still waiting results..should have

this afternoon...hugs,kaye

-- New radiation therapy offers promising results at VUMC

>

> I HAD PET SCAN THIS AM...WILL KNOW RESULTS TOMORROW AFTERNOON...THE

> FOLLOWING OPTION MIGHT BE OFFERED TO ME..IT IS ACCORDING TO THE

PET...THEY

> ARE REALLY EXCITED ABOUT HOW THIS IS WORKING....I WAS THE PATIENT

THAT ALL

> THE LIVER AND ONLCOLIGIST HAD A CONFERENCE ON THIS MORNING...THIS

SOUNDS

> BETTER THAN SURGERY AGAIN..BUT HAVE TO WAIT TO FIND OUT...THEY SAY

MINE IS

> EARLY AGAIN..THANKS TO A GOOD ONCOLOGIST STAYING ON TOP OF

THINGS !!!! IT

> IS THE LIVER AGAIN...WILL UPDATE YOU AS SOON AS I KNOW SOMETHIN...I

KNEW I

> COULD NOT PUT THIS ON THE LIST BUT WANT YOU AND PATI AND SOME TO

KNOW..THIS

> SOUNDS ENCOURAGING FOR SOME OF US..AND THE DRS. ARE SOUNDING REALLY

THRILLED

> AND HAPPY..THINK IT IS A MAJOR THING...CHAT LATER..HUGS,KAYE

>

>

>

>

[Guest guest]

thanks, need all the info we can get...still waiting results..should have

this afternoon...hugs,kaye

-- New radiation therapy offers promising results at VUMC

>

> I HAD PET SCAN THIS AM...WILL KNOW RESULTS TOMORROW AFTERNOON...THE

> FOLLOWING OPTION MIGHT BE OFFERED TO ME..IT IS ACCORDING TO THE

PET...THEY

> ARE REALLY EXCITED ABOUT HOW THIS IS WORKING....I WAS THE PATIENT

THAT ALL

> THE LIVER AND ONLCOLIGIST HAD A CONFERENCE ON THIS MORNING...THIS

SOUNDS

> BETTER THAN SURGERY AGAIN..BUT HAVE TO WAIT TO FIND OUT...THEY SAY

MINE IS

> EARLY AGAIN..THANKS TO A GOOD ONCOLOGIST STAYING ON TOP OF

THINGS !!!! IT

> IS THE LIVER AGAIN...WILL UPDATE YOU AS SOON AS I KNOW SOMETHIN...I

KNEW I

> COULD NOT PUT THIS ON THE LIST BUT WANT YOU AND PATI AND SOME TO

KNOW..THIS

> SOUNDS ENCOURAGING FOR SOME OF US..AND THE DRS. ARE SOUNDING REALLY

THRILLED

> AND HAPPY..THINK IT IS A MAJOR THING...CHAT LATER..HUGS,KAYE

>

>

>

>

[Guest guest]

Kaye,

Hope everything went ok - am thinking of you.

Hugs,

> thanks, need all the info we can get...still waiting

results..should have

> this afternoon...hugs,kaye

>

[Guest guest]

Kaye,

Hope everything went ok - am thinking of you.

Hugs,

> thanks, need all the info we can get...still waiting

results..should have

> this afternoon...hugs,kaye

>

[Guest guest]

, I think I am ok...my Pet Scan did not show cancer..!! have other drs.

looking elsewhere but as of late last night have not found any...so I am so

thrilled..if there is any it is so small he thinks we can do lots of things.

..I am still in shock I thinkl..you know how the mind will do you..wondering

about chemo, surgery,spheres all the stuff and really not knowing anything..

so we wait and let the drs investigate some and hope they don't find

anything...so I really do not know if I am NED OR NERD!!! thanks for all

your positive thoughts and let me know if you have any ideas...hugs,hope you

are ok...kaye

-- Re: Fw: New radiation therapy offers

promising results at VUMC

Kaye,

Hope everything went ok - am thinking of you.

Hugs,

> thanks, need all the info we can get...still waiting

results..should have

> this afternoon...hugs,kaye

>

[Guest guest]

you are so right..if surgery is possible or RFA that is always the best

route..some thing might come back but that much will be gone....thanks for

all the info..hope you are doing ok...thanks for all your help and positive

thoughts...hugs,kaye

-- New radiation therapy offers promising results at VUMC

>

> I HAD PET SCAN THIS AM...WILL KNOW RESULTS TOMORROW AFTERNOON...THE

> FOLLOWING OPTION MIGHT BE OFFERED TO ME..IT IS ACCORDING TO THE

PET...THEY

> ARE REALLY EXCITED ABOUT HOW THIS IS WORKING....I WAS THE PATIENT

THAT ALL

> THE LIVER AND ONLCOLIGIST HAD A CONFERENCE ON THIS MORNING...THIS

SOUNDS

> BETTER THAN SURGERY AGAIN..BUT HAVE TO WAIT TO FIND OUT...THEY SAY

MINE IS

> EARLY AGAIN..THANKS TO A GOOD ONCOLOGIST STAYING ON TOP OF

THINGS !!!! IT

> IS THE LIVER AGAIN...WILL UPDATE YOU AS SOON AS I KNOW SOMETHIN...I

KNEW I

> COULD NOT PUT THIS ON THE LIST BUT WANT YOU AND PATI AND SOME TO

KNOW..THIS

> SOUNDS ENCOURAGING FOR SOME OF US..AND THE DRS. ARE SOUNDING REALLY

THRILLED

> AND HAPPY..THINK IT IS A MAJOR THING...CHAT LATER..HUGS,KAYE

>

>

>

>