Side Effects

General Information | Response Rate & Related Exon Mutations
Dosage | Side Effects | Drug Interactions

Managing Gleevec side effects (New Power Point Presentation)

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Managing side effects:
Nausea
Edema
Fatigue
Rash

The Life Raft Group Side Effects Survey
October, 2001

Introduction

In our April, 2001 Newsletter, the Life Raft Group presented its first survey of the side effects that member patients have experienced with Gleevec. This was a very early study of a small number of participants and gave us our first data on the side effects experienced by GIST patients in the Gleevec clinical trials. Member patients were asked to list up to three significant side effects and to rank each on a scale of low, medium or high. Since this first study, the number of our patient members has increased significantly and a higher dosage of 800 mg per day has been introduced with the phase lll trials. The dramatic responses of most of our members to Gleevec, combined with a growing realization that GIST is becoming a chronic disease, which may necessitate remaining on Gleevec for long periods of time, has prompted us to re-explore the issue of side effects.

In our attempt to do so, we have tried to respond to the suggestions and critiques of our earlier study. Were the side effects present prior to taking the drug? Have they changed over time? Is the ranking of severity consistent amongst members? Do the side effects impact upon our ability to function and, if so, how? Does weight make a difference? How are side effects being managed? How reliable is the reporting of side effects?

This Side Effects Survey builds upon our earlier study, and attempts to be more comprehensive in scope and detail. Our study group has grown to 61 member patients and now includes those on the higher 800 mg per day dose. Members are now asked to list all significant side effects and to rank them over four distinct time periods: the period prior to starting Gleevec: the first 3 months on the trial; the second 3 months on the trial; and the subsequent period on the trial (which ranged from month seven to month twelve). Building upon the work that has been done by the medical community to evaluate pain, we introduced a new scale for rating the severity of side effects. (See Appendix, Exhibit A).

For the first time we attempt to evaluate the quality of medical management of side effects, the sources of information patients rely upon, and the issue of whether patients would minimize the reporting of their side effects in order to remain in the trials.

Objectives

The major objectives of this survey are:

To provide patients/caregivers and physicians with better information about the type and severity of side effects that GIST patients are experiencing with Gleevec.

To evaluate the medical management of these side effects.

To empower patients/caregivers in their relationships with physicians.

Caveats: We repeat our standard caveats. Although many of us come from professional backgrounds, we recognize that we are not professional researchers and our data may be subject to the twin demons of inaccuracy and distortion. Although we have continued to strengthen our survey techniques and our quality control procedures, we are cognizant that patient-based reporting may not always be accurate and that, although we have a larger study group than ever before, we do not know how representative we are of the clinical trials as a whole. Finally, we remain aware of the pitfalls of small numbers. A small change can have a disproportionate statistical effect.

The Side Effects

The survey data is based upon the reports of 61 of the 67 active member patients on board as of August 1, 2001, for a response rate of 91%. Not included were six of our seven members who have died in the past year, a number who have been removed from the trials for lack of response and a significant number of new patient members who have joined us since August 1^st. Included are two Gist-Gleevec patients not on the clinical trial.

Sixty (60) of the 61 respondents, or 98%, reported a total of 273 side effects for an average of 4.6 per patient. Forty-five (45) of the 61 respondents, or 74%, reported 119 severe side effects for an average of 2.6 for the 45. (See Table 1).

The most common side effects reported are fatigue, edema, diarrhea, skin problems, nausea, eye puffiness, cramping, reflux, pain, weight change and eye blurriness. (See Chart 1).

Table 1 Summary Of Reported Side Effects (n = 61)
					Patient Rating By Time Period
Side Effect	No. Rept’d	% Rept’g	No. Severe	%SevereOf No. Reptd	PreTrial	1stQtr	2ndQtr	Subseq Period
Total	273	98%	119	44%	-	-	-	-
Fatigue	38	62%	19	50%	2.7	5.4	4.8	4.0
Edema	33	54%	21	64%	0.6	5.4	4.3	3.1
Diarrhea	33	54%	13	39%	1.5	5.1	4.9	4.6
Skin *	29	48%	13	39%	0.3	4.1	4.3	3.7
Nausea	23	38%	9	39%	0.3	4.3	2.8	2.2
Eye Puffiness	22	36%	4	18%	0	4.0	3.7	4.1
Cramping	19	31%	6	32%	0.7	3.6	4.0	3.7
Reflux	12	20%	2	17%	2.2	4.7	3.4	4.0
Pain	10	16%	5	50%	2.3	3.6	3.5	1.8
H.G.B. (Anemia)	8	13%	2	25%	1.6	3.4	5.0	2.8
Wt Chge +/-10%	7	11%	-	-	-	-	-	-
Eye Blurriness	7	11%	3	43%	0	5.0	4.3	3.0
Liver Enzymes	6	10%	5	83%	2.7	2.3	3.0	-
Fever	4	7%	3	75%	2.0	5.2	5.2	4.0
Mood	4	7%	1	25%	0	1.3	3.0	2.3
Hair Thinning	4	7%	0	0%	0	2.7	4.0	4.0
GI Bleed	3	5%	1	33%	0	1.0	0.5	2.5
White Bl. Cells	2	3%	2	100%	3.5	7.5	3.5	3.54
Neutrophils	2	3%	2	100%	3.5	7.5	3.5	3.5
Dizziness	2	3%	2	100%	0	7.0	5.0	4.0
Miscellaneous**	12	20%	6	50%	2.2	5.6	2.2	3.0

*Skin side effects include patient reported neuropathy.

** Miscellaneous side effects include shortness of breath (2 reported), metallic taste, low blood pressure,

constipation, and difficulty concentrating.

Severe Side Effects
Side effects were rated as severe if they received an average patient rating of 7 or more in any given time period or if they were cited as a reason for stopping the drug or for lowering its dosage level. The greatest number of severe side effects reported were fatigue, edema, diarrhea and skin. (See Tables 1 and 3).

Of those reporting severe side effects, 24% reported only one, 24% reported two and 52% reported three or more. (See Table 2).

Table 2 Number Of Severe Side Effects Reported
No. Severe Side Effects Reported	No. Respondents Reporting	% Reporting
One	11	24%
Two	11	24%
Three	11	24%
Four	8	18%
Five	3	7%
Six	1	2%
Totals	45	99%

Reasons For Stopping And/Or Decreasing The Dosage Of Gleevec

Of the 61 total respondents, 6 had their drug dosages increased, 5 because of tumor growth and 1 because their side effects improved to permit increasing above an initial 100 mg/day level (this was one of the non trial participants). Of the remaining 55 respondents, 24, or 44%, reported having their drug stopped for a period of time, or their drug dosage reduced because of side effects, with edema and skin problems being the most common cause. (See Table 3).

Table 3 Reasons For Stopping And/Or Decreasing The Dosage Of Gleevec
	Number	Percent
Edema	8	33%
Skin *	7	29%
Liver Enzymes	3	13%
Multiple Reasons	3	13%
Eye Blurriness	1	4%
White Blood Cells	1	4%
Fever	1	4%
Totals	24	100%

* Skin side effects include patient reported neuropathy.

Functional Side Effects

We asked each respondent to separately list the functional impact that their side effects were having on their lives. Almost half report having to cope with fatigue. About one third report functional decreases in their physical activities, their sleep, their mood and their appetites. About one fifth report an impact upon their ability to work, to conduct daily activities and to concentrate. Finally, about one out of ten report an impact upon their relationships, general and sexual. (See Table 4).