[CMLHope] Re: Nausea & Diarreah

Sat, 07 Oct 2006 08:21:46 -0700

Well I for one am sticking to Gleevec until if and when it stops working. Even with though Sprycel may have less side effects, at least for now I know the Gleevec is keeping me in remission, so I would rather deal with the side effects then switch to something else. That is just my two cents worth..hehehe
 
Terry

 
On 10/7/06, anjana <[EMAIL PROTECTED]> wrote:

Hi Mike,

I think doctors want to be safe.  It is what Rosemary said.  Gleevec
has been around for 7 years, there is lots of data, so doctors may feel
they may want to see more data on the new drugs before switching.
However, it may boil down to what individual patients want.  I have
been in contact with patients on AMN and Sprycel and most are feeling
much better than on Gleevec with all the fluid gone.  I have even seen
these patients for myself.  When Roy was diagnosed, Interferon was
recommended because Gleevec did not have enough data.  Whatever data
there was from Gleevec at the time was enough to convince us not to go
the IFN route and go to Gleevec and we do not have regrets.  But our
first doc made the same comment- let Gleevec have more data before
taking it.  Same thing is being said with Sprycel except that Gleevec
is a much better drug than IFN in bringing many to remission and
keeping them there so docs may feel why change unless side-effects are
intolerant or patient has not achieved an optimal response.

My husband, Roy, has not achieved an optimal response regarding his
PCR.  He is still not 3-log in 4 years though he is close but his PCR
value has plateaued.  We are seriously thinking of the AMN107 trials
coming to our clinic which is for patients in CCR who have not achieved
PCRU or 3-log with Gleevec.  We have looked at the AMN107 trial data
for resistant patients and talked to AMN patients and the drug is doing
well and patients have more or less a good QOL.

For patients in CCR with Gleevec, if they do switch to a new drug and
do not like the side-effects, they can always switch back to Gleevec.
CML experts I have talked to have said that so I think it will become
quite easy to switch between kinase inhibitor drugs in the future and
we may even have combination kinase inhibitor cocktail therapy.

There has been data, Mike, on newly diagnosed patients on AMN and
although the cohort is small, more data will come out in ASH.  See
below.  All 5 patients achieved a CCR in 3 months after starting AMN
and their PCR values were much lower than those of 800mg Gleevec
patients.  Similarly, see the data of 800mg Gleevec versus Sprycel, the
latter is better tolerated.(note these are Gleevec-resistant patients)
As you say, why not, I also have not seen the harm and I have discussed
with some CML experts.  Our own doc is quite okay with Roy switching if
he wants to.

Mike, I think you are initiating a good discussion.  We have other
drugs now, it is a good idea to at least think about the options.

Best Wishes,
Anjana
caregiver to Roy

Preliminary activity of AMN107, a novel potent oral selective Bcr-Abl
tyrosine kinase inhibitor, in newly diagnosed Philadelphia chromosome
(Ph)-positive chronic phase chronic myelogenous leukemia (CML-CP).
Sub-category:  Leukemia
Category:  Leukemia, Myelodysplasia and Transplantation
Meeting:  2006 ASCO Annual Meeting




Abstract No: 6591
Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting
Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 6591
Author(s): E. Jabbour, F. Giles, J. Cortes, S. O'Brien, F. Ravandi, G.
Borthakur, G. Garcia-Manero, L. Letvak, A. Salvado, H. Kantarjian

Abstract: Background: AMN107 is a novel, highly selective oral Bcr-Abl
inhibitor which is 20-50-fold more potent than imatinib. High response
rates with AMN107 were observed in all CML phases post imatinib
failure. Methods: Study Aims: Evaluate the efficacy of AMN107in newly
diagnosed Ph-positive CML-CP. Study Group and Therapy: Patients with
newly diagnosed Ph-positive CML-CP were treated with AMN107 400 mg
orally twice daily. Results: So far, 13 patients have been treated;
median age 49 (range 24 to 72). Sokal risk at pretreatment: low - 10,
intermediate - 2, high - 1. Five have reached the 3 month evaluation:
all 5 (100%) had a complete cytogenetic response [CGCR] (Ph 0%). This
is compared with a CGCR at 3 months of 36% with imatinib 400 mg/d and
55% with imatinib 800 mg/d in historical data of newly diagnosed
patients treated at M. D. Anderson. The median QPCR with AMN at 3
months was 0.67% (range 0.3 to 3.0), compared with a median QPCR of 8%
with imatinib 800 mg daily. Grade 3-4 myelosuppression was observed in
3/13 and other grade 3-4 side effects in 1/13 requiring temporary
AMN107 interruption for < 2 weeks and resumption at same dose level in
the 3 patients with myelosuppression, and for 6 weeks+ in the patient
with grade 3 elevation of liver enzymes which were reduced to grade 1
on last follow-up. One patient had a transient elevation of total
bilirubin > 3 mg/L which was self limited with continued therapy.
Conclusions: Early results with AMN107 400 mg orally twice daily are
encouraging in newly diagnosed CML.



Dasatinib (D) vs high dose imatinib (IM) in patients (pts) with chronic
phase chronic myeloid leukemia (CP-CML) resistant to imatinib. Results
of CA180017 START-R randomized trial.
Sub-category:  Leukemia
Category:  Leukemia, Myelodysplasia and Transplantation
Meeting:  2006 ASCO Annual Meeting




Abstract No: 6507
Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting
Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 6507
Author(s): N. P. Shah, P. Rousselot, R. Pasquini, N. Hamerschlak, J.
Holowiecki, B. Gerard, D. Dejardin, H. Kantarjian

Abstract: Background: High dose imatinib (800 mg/day) has been shown to
have efficacy in a subset of CML patients with resistance to IM,
although the durability of responses is not well-established. Dasatinib
(BMS-354825) is a novel, highly potent, oral multi-targeted kinase
inhibitor of BCR-ABL and SRC with activity against 18/19 imatinib
resistant BCR-ABL mutants tested in vitro. Methods: START-R is a
multicenter randomized (2:1 ratio) trial of D 70 mg twice daily (bid)
and IM 800 mg/day in pts with CP-CML resistant to prior IM 400 to 600
mg/day. Cross-over was allowed for lack of response or intolerance
(grade 3-4 non hematologic toxicity). D dose escalation to 90 mg bid
was allowed for inadequate response at 12 wks, and dose reduction to 50
or 40 mg bid for drug toxicity. IM dose reduction to 600 mg/day was
allowed. Evaluations consisted of weekly blood counts for the first 12
wks, bone marrow cytology and cytogenetics every 12 wks. The primary
endpoint was major cytogenetic response (MCyR) rate at wk 12. Results:
>From February 2005 to November 2005, 150 pts were randomized of whom
the first 36 pts (D 22, IM 14) are reported. Median age was 57 yrs,
with 12 males and 24 females. Treatment groups were balanced with
respect to CML characteristics; median time from initial diagnosis was
61 months for D and IM; prior interferon 64% and 79%; no prior CyR on
IM 36% and 57%. BCR-ABL mutations were documented in 10 D pts and 1 IM
pt. Dose reductions were required in 8 D pts and 1 IM pt. Complete
hematologic response was documented in 21 D and 13 IM pts. MCyR rate at
12 wks was 45% for D and 21% for IM (7 complete for D and 1 for IM).
With a 95% CI on the difference between D and IM was - 9.9 to +51.2.
Two (9%) D and 11 (79%) IM pts crossed over for intolerance (1 D and 6
IM) or no MCyR (1 D and 5 IM). Grade 3-4 neutropenia or thrombopenia
occurred in 8 and 9 dasatinib pts and in 8 and 2 IM pts. Most common
grade 1-2 non-hematologic toxicities in D and IM groups were diarrhea
(7 and 1 pts), nausea (7 and 7 pts), and facial/peripheral edema (8 and
7 pts). Conclusions: Dasatinib was effective in pts with CP-CML
resistant to IM 400 to 600 mg/day. Preliminary data suggest that D is
more effective and better tolerated than high dose IM. An updated
analysis of all randomized pts will be presented.




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