Question about Xeloda scheduling/timing differences

[zephyr]

There have been several threads about xeloda but I can't find where there's a discussion about different timing schedules. It appears that most people are on cycles of 2-3 weeks on and then a week off. Has anyone been on a shorter cycle and then changed to a longer one - or vice versa? I'm getting ready to begin and my schedule is 2000 mg per day, 5 days on, 2 days off. I'm wondering if the shorter period on the front end will make it more tolerable but I'm also wondering if 2 days is enough time to recover. Thoughts anyone? I know everyone's different but I'm trying to be more prepared this time around with chemo.

Thanks in advance.

[CRguy]

Just as an FYI from 2007.

with neoadjuvant chemoradiation I did 1800 mg twice daily ( 15 minutes after food )
with the morning dose 1 hour before radiation.
Total 28 radiation treatments, 5 days per week over 6 weeks,
Xeloda twice daily, 7 days per week over 6 weeks

Adjuvant Xeloda post surgery :
2,000 - 2,500 mg twice daily ( 15 minutes after food )
2 weeks on, 1 week off for 4 cycles over 2.5 months

Sorry don't have any more up to date info regarding cycles / timings etc other than what's above.

You mentioned "2000 mg per day" is that only once per day ? I am only familiar with twice daily dosing.
Here is the product monograph if you need more specifics
https://www.rochecanada.com/PMs/Xeloda/Xeloda_PM_E.pdf

Best wishes
CRguy

[zephyr]

Just as an FYI from 2007.

with neoadjuvant chemoradiation I did 1800 mg twice daily ( 15 minutes after food )
...
Adjuvant Xeloda post surgery :
2,000 - 2,500 mg twice daily ( 15 minutes after food )
...
You mentioned "2000 mg per day" is that only once per day ?

Best wishes
CRguy

Thanks, CRguy. The 2000 mg per day is divided - 1000 in the morning and again in the evening. Did you notice much difference between 1800 mg and 2500 mg or was it too difficult to tell because the circumstances were different?

[CRguy]

The 1,800 mg twice daily dose was continuous, and only minor fatigue, some diarrhea and "urgency" while getting radiation.

With the 2,000 - 2,500 mg given twice daily doses I had moderately severe hand foot syndrome and major fatigue
( started at 2,000, increased to 2,500 then back to 2,000 dosing because of that )

The reason I asked about your dosing is that 2,000 mg total daily dose seems low, BUTT you are also on Avastin ???
Xeloda has a variable dosing schedule for body size, age, chemo protocol specifications etc.
and many protocols can differ between treatment centers and from country to country.

Cheers
CR

[Beckster]

I was on 3000 mg per day (3 pills in the morning and 3 pills after dinner), which started for 14 days and 7 days off. I took them 10-15 minutes after eating and than I could not eat anything else for 1 hour. However, by th 4th cycle, I developed hand/foot syndrome. Instead of lowering my dose, he had me take 3000 mg for 12 days instead if 14 days with 9 days off. This small decrease really helped the peeling and burning in my hands and feet. I did Xeloda for 6 months without interruption. He did give me the option for 5 days on and 2 days off, but I opted for the 2 week schedule.

Beckster

[Milk Tea]

My husband is on 3000 mg per day (3 of 500mg pills in the morning and 3 pills after dinner), 10 days on and 10 days off. Plus Avastin infusion every 21 days. He has been on this for about two years. The side effects that bothers him the most is bloating (from Xoloda) and high blood pressure (from Avastin).

[zephyr]

The reason I asked about your dosing is that 2,000 mg total daily dose seems low, BUTT you are also on Avastin ???
Xeloda has a variable dosing schedule for body size, age, chemo protocol specifications etc.
and many protocols can differ between treatment centers and from country to country.

The clinical notes state that the low volume of her disease and prior experience with treatment would favor a lesser intensity regimen to start, and then scan again in 8-9 weeks. It's modified based on a European study. If there hasn't been any improvement, the recommendation is to go back on FOLFIRI with the hope to ultimately get to a SBRT or cryoablation. In addition to Xeloda, I'm scheduled for an Avastin infusion every 3 weeks.

... by the 4th cycle, I developed hand/foot syndrome. Instead of lowering my dose, he had me take 3000 mg for 12 days instead if 14 days with 9 days off. This small decrease really helped the peeling and burning in my hands and feet. I did Xeloda for 6 months without interruption. He did give me the option for 5 days on and 2 days off, but I opted for the 2 week schedule.

Thanks, Beckster. I'll keep that in mind. If I find that I don't have enough time to recover, I'll ask for a change.

[betsydoglover]

I've been on Xeloda twice - each time 4000 mg/day. The 2nd time I was having really bad hf syndrome and more fatigue that I expected. We decided to try the 5 days on / 2 days off plan. Those 2 days off felt so good, BUT it didn't give me enough recovery time, so we opted to reduce the dose to 3000mg/day and go back to the 2 week on / 1 day off regimen.

Everyone is different, but this is my experience. Who knows - it might have been different if we had started the 5 day plan from the beginning??????

Take care,

[behconsult]

Connie, I have been on 5,000 mg per day (about 60 rounds) and recently had it cut to 4,000 mg per day. I think it is one of those things that impacts everyone differently. Certainly the longer you are on it the more significant the side-effects. I am on a 7-day a week on and 7 off (breast cancer protocol). My main issue is fatigue from the middle of the cycle to the end. I still work though.

The protocol suggested to you is out of Europe. Dr. Saab stated Europeans do better with it than Americans.

[CRguy]

Dr. Saab stated Europeans do better with it than Americans.

Which may .... have to do with folic acid supplementation of just about EVERYTHING in North America
... leading to an increase in toxicities.

Best wishes
CRguy

[WriterGirl1969]

There have been several threads about xeloda but I can't find where there's a discussion about different timing schedules. It appears that most people are on cycles of 2-3 weeks on and then a week off. Has anyone been on a shorter cycle and then changed to a longer one - or vice versa? I'm getting ready to begin and my schedule is 2000 mg per day, 5 days on, 2 days off. I'm wondering if the shorter period on the front end will make it more tolerable but I'm also wondering if 2 days is enough time to recover. Thoughts anyone? I know everyone's different but I'm trying to be more prepared this time around with chemo.

Thanks in advance.

I took Xeloda (by mouth) mono-therapy in 2016 following my surgery. I was on the normal cycle of 2 weeks on, 1 week off for the first 5 months, but was beginning to see a build-up in the side-effects, so I went digging. What I uncovered in several different medical reports from various sources was essentially that Xeloda was found to reach maximum efficiency at 8 days. Anything beyond that increased side-effects without increasing any benefit.

Here's the link to this study: https://www.nature.com/articles/npjbcancer20166
"...observed that the maximum effect of capecitabine is reached at ~8 days. Therefore, further dosing through day 14 contributes to toxicity without enhancing efficacy."

This finding is what has led many providers to move to the 1 week on / 1 week off method, especially for those experiencing side effect difficulties. I spoke with several people here on the forum who had moved to this regimen (or been on it all along) that had just as much success with it as anyone.

I asked my oncologist about moving to this regimen. Unfortunately, I live in a small town (respectively) and my oncologist felt unwilling to deviate from "the book" on treatment. I ignored what I considered to be his narrow view and moved to the 1/1 regimen anyway, finished treatment, and promptly got myself a new oncologist. I am about to have my 3-year scans, but so far I remain NED.

I hope this info helps.
--Tracy

[zephyr]

Dr. Saab stated Europeans do better with it than Americans.

Which may .... have to do with folic acid supplementation of just about EVERYTHING in North America
... leading to an increase in toxicities.

Best wishes
CRguy

What I uncovered in several different medical reports from various sources was essentially that Xeloda was found to reach maximum efficiency at 8 days. Anything beyond that increased side-effects without increasing any benefit.

The big picture comes into focus!

Wow! Thank you!

[rp1954]

...I took Xeloda (by mouth) mono-therapy in 2016 following my surgery. I was on the normal cycle of 2 weeks on, 1 week off for the first 5 months, but was beginning to see a build-up in the side-effects, so I went digging. What I uncovered in several different medical reports from various sources was essentially that Xeloda was found to reach maximum efficiency at 8 days. Anything beyond that increased side-effects without increasing any benefit.

Here's the link to this study: https://www.nature.com/articles/npjbcancer20166
"...observed that the maximum effect of capecitabine is reached at ~8 days. Therefore, further dosing through day 14 contributes to toxicity without enhancing efficacy."

This finding is what has led many providers to move to the 1 week on / 1 week off method, especially for those experiencing side effect difficulties. ...several people here on the forum ... had just as much success with it as anyone.

...my oncologist felt unwilling to deviate from "the book" on treatment. I ...moved to the 1/1 regimen anyway, finished treatment, and promptly got myself a new oncologist. I am about to have my 3-year scans, but so far I remain NED.

For stage 3s, 5FU intensity rather than long durations repeatedly seems to be a key success factor in permanently rooting out residual cancer cells or clusters. Just like some of the 3-4 month vs 6 month success rates, your catch on the 8 day peak is interesting. My question is for kill optimization, why not 8 0n + 6 off (two week schedule) or 8 on + 7 off (twice a month)? Congratulations on your successes, thinking for yourself, and sharing.

For stage IV or other mCRC, chemo choice is often a decision point after a nominally, completely "curative surgery" - intensity vs maintenance. If still mCRC, maintenance or metronomic may be required. Then the problem becomes intensity, by other means, and duration.

[rp1954]

...Has anyone been on a shorter cycle and then changed to a longer one - or vice versa? I'm getting ready to begin and my schedule is 2000 mg per day, 5 days on, 2 days off. I'm wondering if the shorter period on the front end will make it more tolerable but I'm also wondering if 2 days is enough time to recover. Thoughts anyone? I know everyone's different but I'm trying to be more prepared this time around with chemo.

One more note about my wife's experience with IV vitamin C with oral chemo.

During that first year, before her 2nd surgery, her IV vitamin C doses reached 75 - 80 grams C per infusion, sometimes over 1 gram/minute. We settled on 60 - 65 grams for several years. Several years later, the dose was reduced to 30 grams, and this was insufficient to stop some of her markers from rising, whereas they quickly sank and normalized on 60 - 65 grams, while on enhanced immunochemo.

As for your low, 2000 mg dose with Xeloda, it is possible that you have a natural DPD deficiency that allows 5FU to build up adequately at lower doses. There are tests for this situation too.

[zephyr]

Dr. Saab stated Europeans do better with it than Americans.

Which may .... have to do with folic acid supplementation of just about EVERYTHING in North America
... leading to an increase in toxicities.

Best wishes
CRguy

From a Medscape article I found about Xeloda dosing:

The US has an aggressive policy of fortifying food with folic acid, and requires that all flour, rice, pasta, cornmeal and other grain products are enriched with 140 μg folic acid per 100 g. Similar programs have been initiated in Canada and a number of countries in South America and the Middle East, but are unusual in Europe. One could speculate, therefore, that folic acid supplementation could be a major factor contributing to the perceived excess capecitabine toxicity noted in the US.

https://www.medscape.com/viewarticle/583704_1