All About Gleevec (Glivec)

Gleevec Blood Levels

At the 2008 GI ASCO (American Society of Clinical Oncologists), Dr. George Demetri presented new information about Gleevec blood levels in GIST patients.

Correlation of imatinib plasma levels in GIST patients
A higher concentration of Gleevec in the blood correlates with better clinical outcome according to George Demetri, M.D., of the Dana-Farber Cancer Institute.

In an interview with Peggy Peck on the medpageTODAY website, Dr. Demetri said that the imatinib plasma level was not associated with age, gender, disease bulk, or body weight. “You really need to do pharmacokinetic testing to determine the level of imatinib because there are no clues,” Demetri reported at the Symposium. The findings suggest that “we may have been under-dosing some people,” he said.

New - Imatinib Plasma Levels Predict Clinical Benefits in GIST

Aug, 2009 - George Demetri is interviewed for the Prime Oncology GIST Virtual Journal Club about imatinib plasma levels in GIST patients.

Note: This video is intended for medical professionals outside of the United States. Registration is required to view the video.

This report is based on analysis of the pharmacokinetic data from the original phase II Gleevec trial for GIST (B2222), which started in July of 2000. Plasma levels (plasma is one component of blood) taken after 29 days of Gleevec, were available for 73 of the 147 patients enrolled in the trial. These plasma levels were grouped into quartiles according to imatinib trough plasma concentrations (the level of drug in the blood at its lowest point during the day, just before taking the daily Gleevec capsule).The plasma levels and response rates of these groups are listed in the table below.

Plasma levels and response rates


	Objective response	Median Time to Progression	Objective Response Exon 11 patients
Quartile 1 <1,110 ng/ml	44%	11.3 months	55.6%
Quartile 2+3 >1,110 ng/ml- <2,040 ng/ml	67%	30.6 months	94.1%
Quartile 4 >2,040 ng/ml	74%	33.1 months	92.3%

The authors concluded that, “Exposure to adequate drug levels of imatinib appears to correlate with clinical benefit; patients with the lowest imatinib levels show lowest objective response and shortest time to progression. These results suggest that monitoring pharmacokinetic/ pharmacodynamic relationships may provide novel predictive markers and that exposure to adequate IM trough plasma concentrations (>1,110 ng/mL) is important for optimal clinical response.”

A video report is available on the medpageTODAY website. In the interview, Dr. Demetri explained that “when you give Gleevec or any other kinase inhibitor to a group of patients, they will handle it very differently, some people will have high levels and some people will have low levels… The important part about that is whether we for years might be underdosing people, and whether we perhaps should develop a blood test to check the levels of this drug in people’s blood and have more certainty that there’s actually therapeutic levels in the blood.” Demetri went on to explain that “it’s possible that we could have done this analysis and found nothing at all, but in fact, we saw something that is a bit worrisome for the patients with the lowest levels of the drug.” The next step according to Demetri will be to “… talk with our colleagues, decide exactly how much this is worth pursuing, (and) decide how to mount a large trial.”

Blood Level Testing

Some doctors/institutions are testing imatinib blood levels. Determining an optimum imatinib blood level will probably require a well designed clinical trial that examines multiple factors. For now, the best information (Demetri et al. 2008 GI ASCO) we have is preliminary and suggests that trough imatinib plasma levels should be above 1,100 ng/ml (see above). Testing imatinib blood levels currently has limited availability for GIST patients.

Avantix Laboratories is providing testing of imatinib plasma levels for patients in the United States. At this time, only doctors that are already enrolled in the program can submit samples to the lab. Doctors that are already enrolled, can offer testing to new patients.

Through Avantix, enrolled doctors can order optional free testing kits, send plasma samples for analysis, and view tests results online. This is the fastest way to receive information. It also allows physicians to easily view patients' full test-result histories all at once.

Other programs that we are aware of are listed below.

Country	Program	Lab	Contact	GIST Patients Eligible?
Canada	CML Alliance, Canada	Warnex	Gilles Paquin Sales & Cust. Service Director Warnex Medical Laboratories Tel: (450) 663-6724 x229 gpaquin@warnex.ca	Yes

Australia	GIST Alliance (Australia)		https://www.gistalliance.com.au/Default.aspx	Yes

Helpful Sites

Plasma level testing: what we know, what we don't & what we hope to learn

Is there a role for drug level testing?

Routine mutational and plasma level testing: the time has come

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References

1. Correlation of imatinib plasma levels with clinical benefit in patients (Pts) with unresectable/metastatic gastrointestinal stromal tumors (GIST)
G. D. Demetri, Y. Wang, E. Wehrle, C. Blanke, H. Joensuu, M. von Mehren

2. Drug plasma monitoring in CML and GIST: A case-based discussion.

Egorin MJ, Mauro MJ, Trent JC.

3.Trough imatinib plasma levels in patients treated for advanced gastrointestinal stromal tumors evidence of large interpatient variations under treatment with standard doses.

B. N. Bui, A. Italiano, A. Miranova, S. Bouchet, M. Molimard

4. Personalized cancer therapy for gastrointestinal stromal tumor: synergizing tumor genotyping with imatinib plasma levels.

Marrari A, Trent JC, George S.