Herceptin without chemo - trial

[Unregistered]

I found this on my wanders. It dates back to 2002.

As I read it participants did not have chemo first. I have seen the topic of how effective is herceptin without chemo raised on several occasions.

I have not checked out the figures. At a quick glance I wanted more information as to the actual number taken on drop outs etc., impact of drop outs on stats etc, so I make no comment beyond as usual you need do your own checking.

As the only trial I have come across for hecrceptin without chemo it seemed worth posting.

RB

http://www.jco.org/cgi/content/full/20/3/719?ijkey=c54f0ebc650dabc08aaec44913f535d3c01c6b2a

ABSTRACT


The results of this trial indicate that trastuzumab is active as a single agent and produces durable objective responses in women with HER2-overexpressing breast cancer who have not previously received chemotherapy for their metastatic disease. The response rate was 26%; the clinical benefit rate was 38% in all assessable patients and 48% in the subset whose tumors overexpressed HER2 at the 3+ level by IHC. Although an accurate assessment of the median duration of response was not possible because of censoring, 57% of the responding patients were known to be free of disease progression at 12 months or more of follow-up, underscoring the durability of the responses. These findings are noteworthy in view of the poor prognosis in this population.2-4,10 In addition, patients had lung or liver metastases (67%) because of the requirement for bidimensionally measurable disease. Furthermore, most patients had received adjuvant chemotherapy (68%), which included an anthracycline (50%) or high-dose therapy with stem-cell rescue (12%).

[Lani]

This is indeed old news. Dr Charles Vogel out of Florida published on treating METASTATIC her2 positive breast cancer with herceptin monotherapy long ago. The thinking was, if the patients were going to die within 1-2 years anyway and there disease was extensive and debilitating, why not spare them the chemo. I have heard him speak at conferences. He has been a pioneer in treating breast cancer patients with different chemos (vinorelbine, gemcitabine, capecitabine) long before others were branching out from the "tried and true" anthracyclines and taxanes. Considered something of a trail-blazer and pioneer, look up his publications in Pub Med.
There have been no trials of adjuvant Herceptin monotherapy, as all clinical trials have to give patients the "best available treatment" plus the investigational agent. Trials have seemed to show concomitant chemo and Herceptin better than sequential chemo and Herceptin, so most oncologists feel it would be exceptionally irresponsible and immoral to deny a patient the best possible (known) treatment.

[Unregistered]

Is there not such a thing as patient chioce.

"The results of this trial indicate that trastuzumab is active as a single agent and produces durable objective responses in women with HER2-overexpressing breast cancer who have not previously received chemotherapy for their metastatic disease."

The quote from the above seems to be suggesting Herceptin has benifits without chemo, even if the above did not fall into category of "trial".

What about the young and fertile, what about the already sick - are there not balances to be struck.

Is the system really so inflexible that trained physicians cannot be given the discretion in conjunction with the patient to come up with the best balance for that individual, taking their particular circumstances into account to the best of their ability?

I make no comment on the informal trial or whatever it was as I have not seen the data and am not in any event qualified to do so, but do wonder if there should not be more flexibility. There are so many unknown risks in any event in the early life of any drug as history witnesses, should patients be denied an element of flexibility once a drug has been admitted into the mainstream as "safe and effective" in terms relative to the condition and impact upon that condition.

RB

[Tom]

Dear RB,

I have posted on here regarding this matter before, but not specifically for the purpose of your discussion topic. As you might remember, my Mom was diagnosed with HER2+3 ER-/PR- B/C some time ago. At the time of her original excisional biopsy, the surgeon failed to properly stage her via SNB, removing the one enlarged axillary node only, and not necassarily the sentinel node. The margins were said to be clear at the time of surgery, but only by the minimum commonly used by her surgeon.

Eight months later, her axillary nodes on the same side became enlarged. I insisted the enlarged nodes be biopsied, and they were determined to be positive for malignancy. Subsequently, she underwent an extensive axillary dissection, and 12 of the 20 nodes removed were positive for HER2+3, ER-/PR- malignancy. Both her radiation oncologist and oncologist agreed the the cancer was present in the axillary nodes from the beginning. She underwent another round of radiation to the axilla and supraclavicular nodes, an area which was NOT irradiated in the original field used at the time of her first surgery.

When this nightmare scenario was presented to her oncologist, he agreed to begin single agent Herceptin therapy, even though Herceptin was only then completing it's trials for early stage B/C after and concommitantly with standard chemotherapy regimens, as Mom's age (80 at that time) discouraged the use of any standard chemotherapy courses. She has received weekly Herceptin since, and her cancer has apparently been contained, thank God. Mom's HER2 SERUM ELISA assay, and other diagnostic tests indicate no progression at this point in time. I might also note that my paranoid insistance that she begin the Herceptin at the same time she was receiving her second round of radiation treatment, serendipitously paid off. Subsequent research has since confirmed my suspicions and hope, that giving the two at the same time, would produce a genuine synergistic effect. Apparently, the Herceptin does in fact sensitize the cancer to the radiation therapy, and provides additonal efficacy for cell death.

Of course, I have been giving Mom many supplements, including CoQ-10, Omega 3, flaxseed, flax oil, GLA, oleic acid, curcumin, vitamins C, D3, Gamma-E, folic acid, beta carotene, tons of green tea and green tea extract, and a long list of other supplements discussed here on this site and elsewhere in research abstracts. My approach has alway been one of making the environment as "uncomfortable as possible" for the cancer, while doing everything possible to aid the Herceptin in it's clever mission. The oncologist agrees that we are on the "very edges" of effective treatment, as he describes it, as she has had NO other chemotherapy agents. There is very little research on the efficacy of single agent Herceptin, as I suspect that not many would step outside the accepted protocols of treatment for the disease. I obviously have no proof of my theory, but if Mom continues to do well, I suspect that there might even be some benefit to her being chemo-naive with respect to the many powerful cytotoxic agents commonly used. Research indicates the the toxic nature itself of some of today's modern chemo agents, can produce such a strong inflammatory response, as to actually aid to some degree, the metastatic process. I am of the belief that most cancers arise, at least partially, as a response to chronic, or acute inflammation of otherwise normal tissues. AGAIN, this is ONLY my personal theory, and may be disproved over time with further research.

I am personally glad that Mom is receiving only Herceptin and a carefully crafted group of vitamins and supplements, designed to improve the efficacy of the Herceptin, as well as keep it working for her beyond the point at which her disease would normally begin to develop Herceptin resistance. I understand only too well, that we are really hanging out on a limb with this approach, but we shall see. I don't know if I will agree to submit her to more powerful chemotherapeutic agents should the cancer progress. I pray to God that the Herceptin alone will continue to work it's magic, so that I don't have to make such difficult decisions in the future.

I continue to read with great interest, all of your posts regarding Omega 3 to 6 ratios, and believe that EFA balance plays a huge part in disease management. I thank you for all of your research in that area. I will keep the site informed as to Mom's treatment success as time goes on, so that it might provide one little piece of a huge puzzle regarding treatment courses that might prove effective.

Sincerely,
Tom

[Lani]

Tom, another way to view the serendipity of giving radiation therapy and herceptin at the same time is based on on studies done to develop dendritic cell vaccines and individual vaccines for cancer ie, that the immune system requires antigen to instruct the natural killer cells what to "go after " and perhaps that is also why Herceptin seems to work better with concommitant chemotherapy vs sequential.

A wonderful trial would be to give Herceptin and radiation therapy vs Herceptin and chemo to patients whose age/preexisting conditions do not allow them to tolerate chemo (I doubt the way clinical trials work, merely adding a new agent to the "tried and true" no matter how effective/ineffective rather than trying to find the least amount of the least toxic agent/combination to do the job).

I HOPE we all live long enough to see such a study--not a lot of money in it, not a large number of candidates for the study etc.

[Lani]

Have you ever thought of adding Aleve/naprosyn or clinoril--NSAIDs that have been on the market for 25-30 years so their side effects are well-known (under a doctor's supervision and following her blood count, liver and kidney functions carefully) to her regimen? Or does she have a history of ulcers?

Or clodronate--a new article published this week shows when used in the adjuvant setting it decreases recurrence/bone metastases?

At least with these agents there are clinical studies in humans regarding what dose to use, how often, etc vs. supplements

Just a thought!

[Unregistered]

Lani another cogent post. I had not seen your earlier posts. Sounds like you have done a GREAT job for your Mum.

From my reading n3 pathway / DHA (maybe EPA) have a communality in effect
in HER with Herceptin. I do on nothing more than fresh air have concerns as to the wider impact of blocking fatty acid synthase pathways on critical organs with high long chain fat requirement - brain and eyes, particularly given low n3 and high n6 in the first place may have set up a low inflamation scenario conducive to other factors tipping the balance into cancer. A huge guess is that a combination of FAS blocking and continuing low levels of omega three may further tip towards brain "problems".

Thanks for the post explaining your interest and outlook.

RB

[Unregistered]

Lani I am sure you do but from my reading it is ESSENTIAL to balance the omega threes and sixes, (and maybe err on the side of high three my thought- guess only to balance high levels of sixes in body fats as it is released ).

It is important to watch any oil intake as a lot of a little is still quite a lot - eg olive is 10% or more omega six, canola has significant n6, which in cooking etc can add up, particularly in comparison to say a omea three capsule (without other three supplementation fish flax etc)

Your view on inflamation and chemo was a fascinating lateral leap.

As I am sure you are aware a n3 n6 imbalance does look like underlying feeding body inflamationary processess, and there is constant reference to inflamation in relation to BC. There also appears to be communality of mechanism between the inflamatory pathways and aspects of BC.

RB