Sensitivity of Herceptin Dosing?

[Tom]

I am wondering how critical the dosing schedule for weekly Herceptin is if it needs to be interrupted. For a third time, due to either holidays or office construction, Mom's infusion has to be delayed or moved up. She normally receives her weekly dose on Fridays. I am being asked to choose either to give it to her a day early, or wait over the weekend, effectively receiving it three days late on Monday. I am leaning toward taking her a day early, as I am never comfortable having her serum level of Herceptin drop lower than what it would normally be. On the other hand of course, I also wonder if it is a good idea to have it a day early, perhaps "overdosing" her to some small degree. If you ask an oncologist about this, they always say, "It really doesn't matter". Of course that's what Mom's surgeon said a long time ago when no proper axillary staging was performed, and existing micrometastases laid growing away under her arm for almost a year. If I sound paranoid, I am. I trust the information I find through my own research or facts learned on this website, before I am comfortable with the usual pooh poohing I get from physicians. If any of you have any thoughts on this subject, I would love to hear them. Of course, maybe I am making a big deal out of something simple. I have been known to do just that in the past...lol.

[Lolly]

Tom, all I can tell you is I've had my weekly dose juggled around occasionally and haven't noticed any connection between schedule changes and progression. I've had it a day earlier several times, and once a day later. Once I skipped a week when we were out of town and later this month we're going out of town for 2 weeks so I'll have a double dose the week before.
In my experience, I don't think it's made any difference.

<3 Lolly

[Lani]

is contained in the following article --here is the abstract-

1: Drugs. 2006;66(4):449-75. Related Articles, Links

Trastuzumab : A Review of its Use in the Management of HER2-Positive Metastatic and Early-Stage Breast Cancer.

Plosker GL, Keam SJ.

Adis International Limited, Auckland, New Zealand.

Trastuzumab (Herceptin((R))) is a humanised monoclonal antibody used in the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2), which is associated with clinically aggressive disease and a poor prognosis.The addition of intravenous trastuzumab to first-line chemotherapy improved the time to disease progression, objective response rate, duration of response, and overall survival in randomised, multicentre trials in women with HER2-positive metastatic breast cancer. As such, trastuzumab has become the standard of care in this setting, despite its high acquisition cost and potential for cardiac events, and is licensed for use in combination with paclitaxel (Europe and the US) or docetaxel (Europe). In addition, trastuzumab monotherapy is approved for use in patients with HER2-positive metastatic breast cancer who have previously received chemotherapy for their metastatic disease. Recent data from large phase III trials with trastuzumab in the adjuvant setting revealed significant improvements in disease-free and overall survival. Thus, trastuzumab is also rapidly becoming a standard component of adjuvant therapy for patients with HER2-positive early-stage breast cancer.

PMID: 16597163 [PubMed - in process]

Sorry I don't know how to send a pdf this way!

[Tom]

Thanks Lolly and Lani, for the input. I guess the reason I am so sensitive to Mom's dosing, is that as many of you might remember, Mom is 82, and has received NO other form of the more standard chemotherapeutic agents from the time of her diagnosis. As her oncologist reminded me, and I have always been aware, we are on the very edge of what would be considered a therapeutic level of treatment. There are as far as I know, very few people who have received Herceptin as a first line, single-agent therapy for HER2+ B/C. We have left open the possibility of adding a more conventional chemotherapy agent if we get into trouble, but I have avoided the temptation to have her receive it before such time.

I have tried to give Mom all of the vitamins and supplements, not to mention foods, that will act in unison with the Herceptin, particularly as relates to the promotion of apoptosis, and also to delay the usual reduction in efficacy that it seems to develop over time, i.e. flaxseed, flax oil, GLA, CLA, Omega-3, and Omega-9 EFA's. The complete list of supplements would fill several pages, but include curcumin extract, green tea extract, resveratrol, pure pomegranate juice, and grapeseed extracts.

This is why I am always trying to insure that Mom receives exactly the right dose of Herceptin (weighing her often) at exactly the right time. It seems likely that those small details could mean the difference between it holding the B/C at bay or not. Mom has experienced some ominous symptoms as of late, including night sweats and a chronic low-grade fever. Her blood work looks OK, except for low lymphocyte counts. She just underwent a brain MRI and a PET in the last few days, and we are awaiting the results. Her HER2 serum assay numbers continue to be very low, as does her CA-27,29 (8). I pray daily that we will not find ourselves in the position of needing to move to a more malicious chemotherapy agent, as she has tolerated the Herceptin well over these many months, and continues to have an LV ejection fraction via MUGA of 70 %. I would hate to see her have to deal with the many additional side effects of some of the nasty stuff in order to stay ahead of the Beast, but I am beginning the process of determining which other agent I might request for her should it become necessary.

Thanks again,
Tom

[Lani]

but there have been papers out of Toronto on "metronomic chemotherapy" ie giving tiny doses of chemo daily. It doesn't kill the fastest growing cells as normal doses of chemo do (thus both cancer and fast-growing normal cells such as blood-forming cells and GI lining cells) but rather the cells lining the "new blood vessels" which tumors cause to form to supply them with their voracious appetite for nutrition. These are the weakest link, the Achilles heel. Should your mom ever need more, and should there not be another targeted therapy approved or considered ie, lapatinib or avastin (the latter having possible serious side effects on the kindney, etc), you might want to look into it.

Hope this helps!

[StephN]

Dear Tom -
Glad your Mom is still doing fine. She may have some low grade infection to account for the fever and sweats. That is what happens to me. Her tumor marker is WAY lower than mine. And I am going in for MUGA this afternoon and I will be VERY surprised if it is anything like 70! (Even though I have been working out.)

The deal on the Herceptin window for me has been one day either side of my scheduled infusion. If I am only one day early or late, I do not need a loading dose. So, going over a weekend would probably be too far off.
I am on the 3-week schedule, but used to be on the one-week.
The one-day leeway is the standard my med onc upholds with either schedule.

I would go for the one day early scenario if it were my choice.

[Cathya]

Tom;

I agree with Steph that a one days difference would be better than 3 days. I am also impressed with your mom's muga score. Do you think it's a result of the specific things you give her for her heart or just that she is one of the lucky ones who do not react to herceptin. I'm inclined to think the supplements are really helping and would love a list of heart specific ones you use as I am having trouble with my heart and have been taken off herceptin until things change. It is wonderful that you have been able to keep your mom limited to herceptin only.

Cathy

[Tom]

Thank you for your input. I always feel better with a decision when I have a little "back-up" from friends. I just called the infusion center and told them we would be going for the day early option.

Steph, as far as the fever, I am still baffled by that one. Her white count isn't elevated, but her lymphocyte count is way down. I was wondering if she might have a lymph infection. Circulation of lymph fluid that is impaired because of axillary dissection can result in reduced lymphocyte levels.

Cathy, Mom's baseline MUGA score before she began receiving Herceptin was 80, if you can believe that. I was very thankful for that. After a period of treatment, her MUGA fell to 70, then rose to 74. It is now right around 70. I have been giving her 100 MG of Co-Q10, three (3) times a day. A few months ago, I switched her to another Co-Q10 formulation, made by Life Extension Foundation (www.LEF.org). Their new formulation contains d-limonene, which aids in the absorption of the Co-Q10 itself. Additionally, d-limonene has been found to have anti-tumor properties. I still give her 100 MG, three (3) times a day. I also give Mom a high-gamma form of vitamin E, as well as the D-alpha tocopherol version.

I hope I have answered your questions regarding her MUGA scores.

Thanks Again,
Tom

[snoopy]

Hi Tom

The elimination half life of Herceptin is long (the time it takes for levels of drug in blood to decrease by 50%)

The following is from the UK summary of product characteristics for the product (on www.emc.medicines.org.uk)


"Using the recommended dose, the half-life is approximately 28.5 days (95 % confidence interval, 25.5 –32.8 days). The washout period is up to 24 weeks (95 % confidence interval, 18-24 weeks)"

I was told that the HERA protocol actually allowed the interval between doses to be as long as 4 weeks (rather than the scheduled 3) before "reloading " with herceptin was required.

So an odd day different in administration schedule wouldn't seem to be a problem.

[R.B.]

I know I keep groaning on like a character in a comedy sketch, monty python comes to mind for some reason, but I reiterate from everything I read balancing the omega threes and sixes can have significant positive impact on cardiac health.

Significant diet change should be done in conjunction with your doctor. Fish oil can lead to blood thinning.



RB

[Roz]

I had a first 3 weekly dose (after 9 months of weekly doses) when I planned to go to the UK, and was unable to have the next dose until 4 days after the allocated 3 weeky forward date. As was previously stated, the half life is 28.5 days, so the occasional late dose shouldn't really affect anyone, especially if you then go back to routine doses.

[Lolly]

Tom, just wanted to add, re Lani's post on metronomic dosing; if you do have to add chemotherapy at some point, there is merit in this type of small, continuous dosing. This is what my onc suggested with Xeloda, which we added 2 months ago. I'm on 500mg twice daily, no breaks (others have posted larger doses, with weekends off or a 2-3 week schedule with one week off). I've had NO side effects, and yet am having a very good response (axilla tumors shrinking dramatically).

Addendum: I did have lower blood counts after starting Xeloda, but I've struggled with low blood counts since starting Navelbine again and chalk it up to N's harsher side effects.

<3 Lolly