~Rich66~Update on Mom If You have A Moment

[Rich66]

Ok...

The test appears to have been ELISA by Quest Diagnostics. Says "Reference Range: <12.8 ng/ml"
"Result 14.0"

Looks like Triciak had Herceptin with Navelbine first, then H alone. Not sure how her2 pos she is. Biopsy and serum suggests mom has a mix of her2 pos and borderline/negative. That's what concerns me about using only a targeted therapy...especially with multiple met sites (lungs, liver). I brought up the serum test in case a broader coverage was indicated.
I'll try to keep an open mind on this for now and see if the onc gets back to us. She'll have markers on the 15th and consult/infusion on the 20th.
Doesn't Herceptin alone warrant MUGA monitoring?

[Rich66]

Brand new, interesting and concerning:

J Clin Oncol. 2009 Apr 1;27(10):1685-93. Epub 2009 Mar 2. Links

Utility of Serum HER2 Extracellular Domain Assessment in Clinical Decision Making: Pooled Analysis of Four Trials of Trastuzumab in Metastatic Breast Cancer.

Lennon S, Barton C, Banken L, Gianni L, Marty M, Baselga J, Leyland-Jones B.
Winship Cancer Institute, Emory University, School of Medicine, 1701 Uppergate Dr, Atlanta, GA 30322, USA; LEYLAND@emory.edu.
PURPOSE Trastuzumab is a humanized monoclonal antibody directed against human epidermal growth factor receptor 2 (HER2). Trastuzumab alone or in combination with chemotherapy has been shown to be effective in patients with HER2-positive early and metastatic breast cancer. The extracellular domain (ECD) of the HER2 protein may be shed into the serum and is detectable using an enzyme-linked immunosorbent assay. Correlations have been reported between raised baseline ECD levels and response to trastuzumab, suggesting that serum ECD levels may be useful in making treatment decisions in patients with HER2-positive breast cancer. We investigated this relationship, and also the effect of trastuzumab and chemotherapy on ECD levels, in patients with advanced breast cancer. METHODS This study analyzed sequential ECD determinations on 322 patients treated with six different treatment regimens in four clinical trials. Results Baseline values were available in 296 patients, and of these, 205 (69%) had raised levels (> 15 ng/mL). No clear relationship was found between baseline ECD levels and tumor response. After initiating combination therapy, ECD levels declined irrespective of treatment received and tumor response. For trastuzumab monotherapy, some trend between changes in ECD levels in early cycles and best response was discernable, but the overlap was too broad to be clinically useful. Disease progression was not reliably predicted by rising ECD levels in the majority of patients. CONCLUSION Based on our data, we cannot recommend using serum HER2 ECD levels to make trastuzumab or other treatment decisions for individual patients with advanced/metastatic breast cancer.
PMID: 19255335 [PubMed - in process]

[Rich66]

Ok..that last post of mine sure questions the benefit of the serum Her2 test. But..in the meantime, mom has received Herceptin. My question is whether an every three weeks schedule has been validated. The lit included with Herceptin mentions weekly.

There is this study:
1: BMC Cancer. 2007 Mar 20;7:50. Links
Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial.

De Maio E, Pacilio C, Gravina A, Morabito A, Di Rella F, Labonia V, Landi G, Nuzzo F, Rossi E, Silvestro P, Botti G, Di Bonito M, Curcio MP, Formichelli F, La Vecchia F, Staiano M, Maurea N, D'Aiuto G, D'Aiuto M, Thomas R, Signoriello G, Perrone F, de Matteis A.
Clinical Trials Unit, National Cancer Institute, Via M, Semmola, I-80131 Naples, Italy. linda.demaio@uosc.fondazionepascale.it <linda.demaio@uosc.fondazionepascale.it>
BACKGROUND: After two studies reporting response rates higher than 70% in HER2-positive metastatic breast cancer with weekly trastuzumab and vinorelbine, we planned a phase 2 study to test activity of the same combination, with trastuzumab given every 3 weeks. METHODS: Patients with HER2-positive metastatic breast cancer (3+ at immunohistochemistry or positive at fluorescence in situ hybridization), PS < or =2, normal left-ventricular ejection fraction (LVEF) and no more than one chemotherapy line for metastatic disease were eligible. Vinorelbine (30 mg/m2) was given on days 1 & 8 every 21 and trastuzumab (8 mg/kg day 1, then 6 mg/kg) every 21 days). A single-stage phase 2 design, with p0 = 0.45, p1 = 0.65, type I and II error = 0.10, was applied; 22 objective responses were required in 39 patients. RESULTS: From Nov 2002 to May 2005, 50 patients were enrolled, with a median age of 54 years (range 31-81). Among 40 patients eligible for response assessment, there were 7 complete and 13 partial responses (overall response rate 50%; 95% exact CI 33.8-66.2); 11 patients had disease stabilization, lasting more than 6 months in 10 cases. Response rate did not vary according to patients and tumor characteristics, type and amount of previous chemotherapy. Within the whole series, median progression-free survival was 9.6 months (95% CI 7.3-12.3), median overall survival 22.7 months (95% CI 19.5-NA). Fifteen patients (30%) developed brain metastases at a median time of 12 months (range 1-25). There was one toxic death due to renal failure in a patient receiving concomitant pamidronate. Twenty-three patients (46%) had grade 3-4 neutropenia, 2 (4%) grade 3 anemia, 4 (8%) febrile neutropenia. Two patients stopped treatment because of grade 2 decline of LVEF and one patient because of grade 2 liver toxicity concomitant with a grade 1 decline of LVEF. One patient stopped trastuzumab after 50 cycles because of grade 1 decline of LVEF. CONCLUSION: Although lower than in initial studies, activity of 3-weekly trastuzumab plus vinorelbine fell within the range of results reported with weekly schedules. Toxicity was prevalently manageable. This combination is safe and active for metastatic breast cancer patients who received adjuvant taxanes with anthracyclines.

[Rich66]

1: Ann Oncol. 2007 Dec;18(12):1969-75. Epub 2007 Sep 9. Links
Optimizing clinical care of patients with metastatic breast cancer: a new oral vinorelbine plus trastuzumab combination.

Catania C, Medici M, Magni E, Munzone E, Cardinale D, Adamoli L, Sanna G, Minchella I, Radice D, Goldhirsch A, Nolè F.
Division of Medical Oncology, Unit for Medical Care, Department of Medicine, European Institute of Oncology, Milan, Italy. chiara.catania@ieo.it
BACKGROUND: Trastuzumab (T) combined with i.v. vinorelbine (i.v.VNR) is an active regimen for patients with advanced breast cancer (ABC). In order to further improve quality of life of patients undergoing treatment for ABC, a new regimen using oral vinorelbine (oVNR) (d1 + d3) plus q3wks T was tested (ToVNR). PATIENTS AND METHODS: Thirty-nine patients with ABC, human epidermal growth factor receptor 2/neu 3+ or FISH positive received 288 treatment cycles with T 6 mg/kg (loading dose, 8 mg/kg) on d1 and oVNR 55 mg/m(2) on d1 + d3, q3wks until disease progression or unacceptable toxicity. RESULTS: Thirty-seven patients and 286 treatment cycles were evaluated (two patients were lost to follow-up). Treatment was very well tolerated. Two patients had complete response (CR), 14 partial response (PR), 17 stable disease (SD) and four disease progression (PD) (overall response rate: 43%). Clinical benefit rate (CR + PR + SD >24 months) was 73%. Median time to progression was 8.9 months (range 2-27) and median duration of response was 10.9 months (range 2-27). CONCLUSIONS: The ToVNR combination is active and very well tolerated. It favorably compares with the combination of T and weekly i.v. administered VNR, allowing a more convenient once every three weeks hospital admission and leaving patients and care providers free from the unpleasant effect of i.v.VNR.

[Rich66]

Ok..my propellor in training is sputtering trying to distinguish the results between weekly and triweekly Herceptin... But I am still asking if any of you folks did Herceptin without heart evaluation.

[Jackie07]

Rich,

My 3-week chemo+Herceptin was continued with weekly Herceptin when my heart function decreased more than 10%. Then I had to stop completely because of further decline. MUGA score was the criteria. Although this time when I had the scar tissue removed (thought they were new lumps) I only had echocardiogram before surgery.

[Rich66]

found this in a powerpoint presentation. Note higher loading dose (weekly is 4mg/kg, then 2 mg/kg):

Pharmacokinetic data for Herceptin® support the use of a 3-weekly dosing regimen
lTo maintain drug exposure at levels similar to those observed with the weekly regimen, Herceptin® must be administered at 8mg/kg followed by 6mg/kg 3-weekly
lThe 3-weekly regimen has been shown to be well tolerated and effective in combination with paclitaxel and alone
lThe 3-weekly regimen is being used in major trials investigating Herceptin® as adjuvant therapy
lLoading schedules will be investigated to determine whether Herceptin® steady-state levels can be attained more rapidly while maintaining safety

[Rich66]

Ok..out of curiousity I called to find out what loading/initial dose mom got: 4mg/kg..to be followed by 6mg/kg. Ok...so 3wk is usually 8mg/kg loading with 6mg/kg after. So..does it make sense to have half the normal loading dose and check for results in 3 weeks? Seems like underdosing for the first 3 weeks would limit chance of positive signs. Maybe this was done to minimize side effects but it could confuse whether it is helpful.
Thoughts?

[Debbie L.]

Hi Rich,

Maybe the person reading the dosing to you got it wrong? The whole meaning of a "loading" dose is to get a therapeutic level into the system at the onset with a higher dose initially, and then to maintain it thereafter (with, duh, the "maintenance" dose). I'll be eager to hear what explanation they give you for this weird dosing. Every reference that I can find has just the two options, as you noted, for either weekly or q3 weekly dosing. That seems to be the same whether it's given adjuvantly or for stage IV and regardless of what else it's given with.

And some kind of cardiac monitoring is standard, per NCCN guidelines and others, for Herceptin with adjuvant treatment, but I can't find mention of cardiac monitoring in the guidelines for advanced disease. It seems like at least a baseline LVEF would be needed.

Debbie Laxague

[Sheila]

Rich/Debbie
Just as an FYI
I have had Herceptin weekly, every 3 weeks and every 2 weeks...which is my current schedule....my muga and or Echos have not varied with any of the schedules....my schedule is based on convenience.

[Rich66]

I can wrap my head around the idea that different doses can keep an appropriate level of Herceptin in the system for a given interval. I have not, however, seen anything to support a 1 week loading dose for a 3week interval.
This seemed to catch the nurse who read it to me by surprise. She reread it and told me the usual dosages and that she had no explanation for the dosage. She said she could see my previous request for clarification attached to the chart and would have the onc call me the next day which would have been yesterday. I try to be respectful and patient but this kind of thing makes me really wonder.

[Rich66]

Talked to the Onc and he said the lower initial dose was to gauge reaction. Looks like she will get the 6mg/kg dose Monday.
Mom had her labs yesterday and general numbers were pretty good, waiting on CA27. She also had her MUGA which was 51 back in '05. Yesterday it was 65. Pretty surprising since she hasn't been doing anything to bolster her heart. Is the test prone to variation?

[Believe51]

Rich, I have noticed that you too stay up all hours of the evening, not tonight but this week. Caregivers gotta sleep you know (yeah I wish).

Wanted to hear how Mom is. Although I do not post on this thread frequently, I do keep up with it the best I can. You are such a special son and I know that is one heck of a Mom too!! Please update us when you can, you are probally sleeping right now....hahaha.>>Believe51

PS: I will be able to start releasing public information about Rose's Foundation which is well beyond a Rexin-G project. This is big and in order to be a non-profit organization she has to take steps legally. June should be her starting date and so far she is right on target. Talk soon......much more than just Rexin-G

[Rich66]

I'm typing from onc office computer.
Mom is still feeling well. I sense there has been more coughing lately but it's a complicated situation with both emphysema and lung mets.
Mom just had labs then chest/ab scans. Fortunately, I asked about the Her2 serum test, thinking I would nudge them to exepedite sendout to California (We're in WI). Well...apparently it was in the orders but wasn't being sent out. Someone missed the order. Another instance backing up vigilance which sometimes is interpreted as paranoia. At least today, the lab tech thanked me for asking them about it. Sure wish it wasn't necessary. HER2 serum might not be back in time for Monday's appointment with onc. We'll see. I haven't been a fan of the Herceptin monotherapy approach but the onc seems to want to gauge things that way, at least to start. If scans show progression, my thought is the serum test, if levels drop >20%, might still suggest benefit of continuing Herceptin. Seems like the new info suggests continuing H after progression anyway. or..switch to Tykerb or H+T. Onc said (via nurses) that scans will dictate next steps, not Her2 ELISA. So...why are we doing it? Ah..always full of questions. Do you folks ever wonder what really goes on in oncs heads?
FWIW, went with my Dad to his cardiologist yesterday. He went through the lengthy list of problems he has and told him he's surprised he's still alive. Basically told him not to expect much in the way of recovery at his age after extended hospital stay. Not sure this is too helpful. Watched my Dad's eyes well up as he was secured in the medical transport van. Dunno...how about a different approach commending him on pulling through and encouraging him to strive for the moon? I guess some lean towards the ole glass half-empty approach. That mentality is why I camped out in the hospital for weeks like a medi-cop. But I digress..
(sigh)
Hey, I look forward to news on Rose's project! More warriors to the front line please

[Believe51]

Rich, this battle is just full of so many circumstances so keep asking those questions and 'see the medi-cop, be the medi-cop'! Any intervention we can assist we should and in the start I did feel very demanding and paranoid, but within reason. Nudge if you feel you want to and never look back. Please DO overlook at times like this that we think we may have dropped the ball. Recently Ed had a hold up in a petscan we were waiting for an approval on that should have never happened. Luckily for us he had a bone scan and spent time gaining some weight in between researching. I know you are not beating yourself up about this but wanted to just mention it to you.

I will await the results of Mom's testing and know someway, somehow it will help in any decisions she may have to make. I am amazed by her sheer beauty and fight, and I must say I have sort of adopted her in a sense. So please know she is constantly coming into my mind. Continued prayers for Mom and Dad.

As for Dad, well I am sometimes disappointed in the way some descibe the situation to our loved ones and even the patient in the next bed. You are right in feeling that there are more gentle ways to address that list of his. I have found out that it is my job as Marie, to jump in and supply what I watch and feel is lacking in the hard truths. I am so sorry that he had to be kicked in the knees but I know you will try to help him past that. Dad too is an amazing fighter and I can see where you get it from with these special people, what a beautiful family you have.

I listen to you talk and wish I could empty that full plate of yours, I know you too are full. But this is the story of Love and as your friend I am so blessed to be able to hear your story and learn from it. Always in my thoughts and thanks again for keeping us posted on what is happening in this journey and for helping us on ours.>>Believe51

PS: Did you ever get the results of the ear wax sample you sent out?? Haha..You are one silly person.

Gotta go back and pray for Donna's Mom.

[Rich66]

Progression in 2 spots in lung.....CA27=36.9 from previous 22

[Believe51]

Rich, keeping an eye on Mom and sending her a hug. She has had a rough time lately and I am sorry for her and those whom love her. You seem to have things in order for her and this is the best we can do at times like this. One step ahead of things, poking, prodding, asking.....

Your research and devotion for Mom is something to be admired from any standpoint. Keep up the great work for her and Dad. Please let us know her information as it filters in and when you are not sleeping (smiling).

I am praying for Mom, Dad and you as you embark on yet another battle. Peace to you, Rich.>>Believe51

[Rich66]

Going to see Onc Monday...any suggestions welcomed. I'm assuming he will view this as Herceptin failing and need for new chemo..possibly navelbine. Not sure if serum her2 will be in yet.

[StephN]

I don't think it is Herceptin "failing."

How many treatments did she have!!?? Plus the demi-loading dose.

Maybe they can add a small dose of Navelbine to the Herceptin. Or Xeloda, which you know is a pill.

Dads don't deserve to be bound in a wheelchair, but that is also what happened to my Dad. He could not get off the ventilator. But he never lost his big smile.

[Rich66]

Onc feels growth could have happened in the 2 weeks between end of Xeloda and start of Herceptin. She is, as I type, getting another 3 wk dose of H alone. Will be rescanned in 4 weeks. Mom said "It's going to be a long month." Indeed.
Still waiting on serum her2 results.
Discussed possibility of Tykerb/Herceptin combo...with possible insurance issues. I note some here have had H+T+Xeloda. I had passed along the bicarb raticles and he mentioned he had tried that in the past without benefit. I don't know what protocol etc. it's still a helluva idea...if it worked. He mentioned a novel protocol he is working on involving Tamoxifen..but not in an ER+ dependent manner. Going to talk more about that next visit.