Download Selling L-Carnitine - Oncology - Cancer Fatigue

L-Carnitine
Cancer Fatigue
ESMO 2010
2012
Key Clinical Evidence for L-carnitine
in Cancer Fatigue
Mancinelli
Carboplatin: ↑carnitines urinary excretion
De Greve
Decreased carnitine, correlates with fatigue
Hockenberry
Decreased carnitine, correlates with fatigue
Graziano
LC reduces fatigue and improves carnitine levels
Cruciani
LC reduces fatigue, depression and improves sleep and carnitine levels
*Vinci
Lower plasma carnitines in neoplastic cachectic patients than in neoplastic
patients
*Gramignano LC reduces fatigue, oxidative stress and improves QoL, BMI
*= not included in the selling outlines
ESMO 2012
Mancinelli - Low Carnitine levels in carboplatin
treated cancer patients
Study evaluated the effect of carboplatin
treatment on plasma and urine levels of Lcarnitine (LC) and Acetyl-L-Carnitine (ALC) in
cancer patients.
Patients:
11 patients with various types of cancer.
Results:
Carboplatin treatment significantly increased urinary
excretion of LC and ALC, without affecting plasma
levels.
ESMO 2012
De Greve - In breast cancer patients treated with
anthracycline
Study evaluated L-carnitine levels and fatigue in
breast cancer patients on anthracycline-based
regimens
Patients:
12 patients after 6 cycles of chemo + 6 months followup.
Results:
• Found decreased levels of both free carnitine
(-33%) and acyL-carnitine (-22%).
• Increased fatigue levels were observed in patients.
.
Conclusions:
Low plasma L-carnitine levels in early breast cancer patients on anthracycline-based
chemotherapy could be responsible for the fatigue observed in these patients.
ESMO 2012
Hockenberry - Carnitine plasma levels in patients
receiving
Study examined fatigue and L-carnitine plasma levels in
children/adolescents before and after chemotherapy
Patients:
67 children and adolescents between 7 and 18 years of age
receiving first or second course of cisplatin, doxorubicin or
ifosfamide chemotherapy
Results:
• There was a significant increase in free and total
carnitine levels after treatment fot patients receiving
doxorubicin than patients receiving cisplatin ir
ifosfamide.
• Increased fatigue and decreased carnitine levels were
significantly correlated a week after chemotherapy in
children/adolescents who had received prior
chemotherapy.
Conclusions:
This study provides support for a relationship between carnitine decreased levels and fatigue in
children/adolescents with cancer.
ESMO 2012
Graziano - Non-anaemic cancer patients
Study investigated the efficacy of L-carnitine in the
treatment of chemotherapy-induced fatigue in nonanaemic cancer treatments (principally platinum based).
Patients:
50 patients, open study
Treatment:
1 week oral L-carnitine 2g twice daily
+ 2 weeks follow-up
Results:
• After 1 week of treatment with oral L-carnitine 2g bd, all
patients achieved normal plasma carnitine levels (> 30 µM)
• Fatigue (FACT-F scores) significantly improved in 45/50
(90%) patients (p<0.001)
• Fatigue scores remained constant during the two weeks
following the suspension of L-carnitine treatment.
Conclusions:
Study demonstrates the efficacy of oral L-carnitine in the treatment of chemotherapy-induced fatigue
in non-anaemic cancer patients
ESMO 2012
Cruciani – Advanced cancer patients
Dose-finding study to determine the safety and
tolerability of oral L-carnitine supplementation in
carnitine-deficient patients with advanced cancer.
Patients:
27 patients, open label study
Treatment:
1 week of various doses of oral L-carnitine solution from
250mg/day to 3g/day
Results:
• Symptoms of fatigue, depressive mood, quality of sleep,
significantly improved in all patients after 1 week of
treatment with oral L-carnitine
• A dose-response relationship was observed for Fatigue in
L-carnitine responders
• Oral L-carnitine supplementation is very well tolerated up
to dose of 3000mg/day.
Conclusions:
Phase I/II study shows L-carnitine to be safe, tolerable and effective at reducing fatigue in advanced-cancer
patients undergoing chemotherapy
ESMO 2012
Vinci - Low Carnitine levels in neoplastic cachectic
patients
Study investigated carnitine levels in cancer
cachectic patients vs healthy controls
Patients:
46 neoplastic cachectic patients / 30 neoplastic
patients / 30 healthy pts.
Results:
Serum carnitine levels were lower in neoplastic
cachectic patients when compared to neoplastic
patients with good nutritional status and healthy
controls.
Conclusions:
Carnitine levels showed to be lower in neoplastic cachectic patients when compared to healthy
controls
ESMO 2012
Key Clinical Evidence for use of L-carnitine in
Cancer Fatigue
Study investigates the effect of oral L-carnitine on
Fatigue, QOL, Nutritional status in advanced
cancer patients
Patients: 12 patients
Treatment:
L-carnitine 6g/day (2g tid) oral, 4 weeks
Results:
• Fatigue, QoL and nutritional status of patients
significantly improved after 4 weeks treatment with
6g / day L-carnitine.
• LBM and appetite were also improved.
.
Conclusions:
Study highlights what was previously investigated by Vinci in 2005 on cachectic patients.
ESMO 2012
Sezen - L-carnitine significantly reduced brain and
retina damage
Study evaluated the effect of L-carnitine treatment
on brain and retina radiotherapy-induced damage
in a rat model
Treatment:
Animals received treatment 4hrs before irradiation
and for 10 days after irradiation)
L-carnitine:
200 mg/Kg/d, ip
Irradiation:
total cranium radiotherapy with cobalt-60 (15Gy,
single dose
.
Conclusions:
After 10-days treatment with L-carnitine a significant reduction is observed in:
1) total cranium irradiation-induced brain and retinal damage
2) total cranium irradiation-induced brain oxidative stress
ESMO 2012
L-Carnitine
Rational in Cancer Therapy Side Effects
ESMO 2012
L-Carnitine in Cancer Therapy Side Effects:
Selling Outline
HOOK
You are no doubt aware that cancer
therapies may severely affects patients’
quality of life.
Fatigue is a commonly reported symptom
resulting from chemotherapy, a condition
further worsened by chemotherapy-induced
carnitine deficiency.
MAIN PART
Carnitine is an endogenous substance
which plays a key role in energy
metabolism, and its depletion in cancer
patients, is a condition often under
diagnosed.
ESMO 2012
In 11 cancer patients,
Mancinelli showed that ….
ESMO 2012
… carboplatin treatment was associated with a marked
urinary loss of carnitine.
So, the question is: Could carnitine depletion be
associated with the symptoms of fatigue in cancer
patients?
ESMO 2012
De Greve observed 17 early breast cancer
patients on anthracycline based chemotherapy.
ESMO 2012
This prospective study demonstrates a
clinically significant worsening in fatigue
symptoms, associated with a decrease of
carnitine levels by more than 30%.
Therefore, in cancer patients, carnitine
depletion secondary to chemotherapy, seems to
be associated with fatigue.
Why not treat these subjects with L-Carnitine?
ESMO 2012
These observations have been recently
confirmed by Hockenberry in this study on
children/adolescents receiving cisplatin
ifosfamide or doxorbucine.
ESMO 2012
We can see that there is a free carnitine reduction
when the children had already been treated with
chemotherapy.
ESMO 2012
Equivalent results for the total carnitine plasma
levels. Not surprisingly also in this study there
was a significant relationship between the
reduced carnitine levels and the fatigue.
ESMO 2012
A milestone on the potential role of carnitine
administration for treating cancer fatigue is the
paper by Graziano, involving 50 non-anaemic
cancer patients.
ESMO 2012
After 1 week of treatment with oral L-carnitine (4g/d), all patients
achieved normal plasma carnitine levels, and Fatigue significantly
improved in 90% of patients.
Moreover, Fatigue scores remained constant during the two weeks
following the discontinuation of L-carnitine treatment.
ESMO 2012
Chemotherapy-induced fatigue is not the only symptom
alleviated by carnitine. Many cancer patients experience
radiotherapy-induced organ damage.
Preclinical data shed light on the possibility that L-carnitine
might alleviate irradiation damage
ESMO 2012
Due to its antioxidative properties, L-carnitine
significantly reduced brain (look at the
reduced number of pyknotic nuclei) ….
ESMO 2012
… and retina damage (look at
the normalized thickness)
So, as you can see, treatment with Lcarnitine by correcting carnitine
deficiency and reducing oxidative stress
might result beneficial ameliorating
cancer patients’ quality of life.
ESMO 2012
L-Carnitine in Cancer Therapy Side Effects:
Selling Outline
OVERALL
CONCLUSIONS
So, as you can see, treatment with LCarnitine by correcting carnitine
deficiency and reducing oxidative
stress might result beneficial
ameliorating cancer patients’ quality
of life.
ESMO 2012