A Phase II Study of Curcumin and Vitamin D in Previously Untreated Patients with Early Stage Chronic Lymphocytic Leukemia (CLL) or Small Lym

[Cllcanada]

Background: Current therapies for CLL/SLL have frequent toxicities, are non-curative, and several trials have demonstrated that early treatment of the disease doesn’t result in longer overall survival. In high doses, both curcumin (CM), from turmeric, and vitamin D (VD) have been shown to be safe in multiple clinical trials of solid tumors. Curcumin was shown to disrupt CLL cell interactions with the microenvironment, induce apoptosis independent of DNA damage, and upregulate vitamin D receptor (VDR) in malignant lymphoid cells. We hypothesized that the combination of CM and VD is safe and active in CLL/SLL and would delay disease progression.

A total of 35 patients (pts), 51% males, were accrued to the trial, 30 (86%) were evaluable for response. Median age was 60 years (range 45-80). Most had CLL (97%); 51% were Rai stage 0 and 49% were Rai stage 1. Cytogenetic abnormalities included del13q14 (37%), trisomy 12 (11%), del 11q22 (11%) and del 17p (3%); 20% had ZAP-70 levels >20%. Median number of cycles received was 5 (range 1-6) and treatment was well tolerated overall. The most frequent adverse effects (AE) were diarrhea/gastrointestinal upset in 69% of patients (14% were grade 3). No serious AEs were observed. Eighteen pts (51%) completed all 6 cycles of treatment; 10 (29%) withdrew consent, 4 (11%) discontinued treatment because of diarrhea, and 3 (9%) patients progressed on treatment. Best response was stable disease in 28/30 (93%) evaluable pts. After a median follow up of 29 months, EFS was 72.0% (95% CI 52.1 - 84.7%), 74.1% (95% CI 58.7-89.6%) had not started new CLL treatment, and OS was 100%. Median VD-25-OH levels were 28.75ng/ml (range 12.5-55.6) at baseline and 49.5 ng/ml (24.8-69) at 28 days. Median COG/COS levels were 15.8 (2.73-75)/6.71(0-33.5) and 18 (0-75.9)/7.21(0-35.2) ng/ml at 8 and 28 days, respectively. Flow cytometric analysis of CLL cells showed no significant change in VDR or Phosphorylated-NF-κB with CM-VD treatment.

Conclusion: Curcumin and high-dose vitamin D combination is safe and well tolerated in patients with early stage CLL. Although no responses were seen, the majority of patients maintained stable disease on treatment. Longer follow up is planned on this study to determine long – term CLL progression rates of patients treated with CM-VD.

ASH 1875

ash.confex.com/ash/2018/web...

[Redlion]

Just wondering if curcumin + vit D would negatively interact with Ibrutinib treatment.

[Cllcanada Top Poster CURE Hero in reply to Redlion]

That’s a good question for your CLLdoctor... usually they want patients to stop all this, so they know what they are dealing with, if treatment should go sideways... and adverse events appear...

~chris

[OldManNiko in reply to Redlion]

I can only speak to my experience, my doctor and the pharmacist asked that I discontinue curcumin when starting Imbruvica (Ibrutinib). They (the pharmacists representing Pharmacyclics) said they are aware of an interaction that increases AEs.

[Lola69]

I take a weekly Vit D pill and sprinkle curcuma on my foods. ( Moroccan curcuma ) everything is under control. Presently on imbruvica

[Hoffy]

So how does high does Curcumin + Vit D compare with high does green tea. Green tea ( ECGC) showed clinical response - so it is stronger?

Thanks,

Hoffy

[Cllcanada Top Poster CURE Hero in reply to Hoffy]

The ratio is 10:1 EGCG to curcumin on alternate days... not any curcumin, it should be liposome coated... piperine works but not terribly well...

ncbi.nlm.nih.gov/pmc/articl...

[SeymourB]

Chris -

"The most frequent adverse effects (AE) were diarrhea/gastrointestinal upset in 69% of patients (14% were grade 3). No serious AEs were observed. Eighteen pts (51%) completed all 6 cycles of treatment; 10 (29%) withdrew consent, 4 (11%) discontinued treatment because of diarrhea"

Grade 3 may not be life threatening, but I believe that it's severe. The fact that 11% discontinued due to diarrhea seems like a strong indicator of trouble to me.

About a year ago, I had what was diagnosed as a gall bladder attack. I had been adding a level teaspoon of McCormick turmeric to various foods twice a day, along with butter or margarine and black pepper. The night before the attack, I also had some gumbo and french bread and butter, which I thought triggered the attack.

My liver stats went wacky, and monocytosis showed on automatic CBCs, but a mix of monocytosis and neutrophilia on manual CBCs has continued for almost a year now. I had let all my doctors know about the turmeric experiment, but none seemed familiar with it. I'm still waiting on other tests regarding the continue odd results.

When the gastroenterologist removed the stone, he noted that the ultrasound done shortly after the attack showed it had not blocked the duct, and that he saw no inflammation when he removed it. But he said that that does happen with gall bladder attacks.

By the time he had removed it, I had stopped turmeric for over a month, though. I have used turmeric in food only sparingly since then, mostly as part of an occasional curry. I do have a sensitive stomach, and GERD, IBS-C, and a mild gastroparesis. I hate to think that I sacrificed my favorite gallbladder a month later due to an experiment that went wrong!

I have read comments on consumerlab.com and elsewhere that some people do indeed have trouble with turmeric or curcumin. They note that animal studies do show liver problems with long term use of curcumin, but no long term safety studies have been done on humans as of their last update (Sep 28, 2018).

So I would advise those who like to experiment on themselves like me, pay attention to your body. Get comprehensive metabolic panel soon after venturing on any high dose herbal therapy. Let all of your doctors know what you are doing.

=seymour=

[SeymourB in reply to SeymourB]

I would add that turmeric has many more ingredients than just curcumin. Food is chemically complex. So tests of curcumin alone may not apply to turmeric and vice versa.

=seymour=

[AnneHill in reply to SeymourB]

Hi, I had gallstones when I was in my thirties. A friend told me to cut out all fat. Although I was booked for op I still went on holiday and asked for plain food. No butter or I would spend the night throwing up bile. If you did have a problem, it would be the butter that caused the symptoms. I take vit D and omega 3 but no other supplements. Its always interesting to read about supplements. How many folk eat a balanced diet? When we read this forum we assume most ate healthy foods but do they? Anne

[SeymourB in reply to AnneHill]

Anne -

I think healthy foods is a much trickier topic. What's healthy for one, may be a disaster for another.

I also have supplemented with vitamin D3. I try to eat omega3s, but found that fish oil pills really upset my stomach. I do better with walnuts, olive oil, and deep sea fish. I eat high fiber, but avoid some kinds, especially inulin (chicory root), that cause bloating, belching, and spasmodic pain based on my FODMAP challenge experience.

I agree that fats are the main problem with gall bladder attacks - that's why I suspected the gumbo and french bread with butter originally. I immediately stopped all fats while in the acute pain phase, and minimal fats for several months until the surgeries could be scheduled. Even healthy fats would have caused it, though, I think.

The gallbladder is now gone the same way my appendix and wisdom teeth went. Aliens are surely building a master race from my discarded body parts. ;^)