attn: Rolepaul, Marvass et al Review article on IT herceptin stresses need 4 ClTrial

[Lani]

How about it then????

Breast Cancer Res Treat. 2013 Apr 16. [Epub ahead of print]
Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis.
Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M.
Source
Department of Clinical Therapeutics, Alexandra Hospital, Medical School, University of Athens, Athens, Greece, florazagouri@yahoo.co.uk.
Abstract
Leptomeningeal carcinomatosis (MC) represents an uncommon, but devasting manifestation of metastatic breast cancer. This is the first systematic review/pooled analysis to synthesize all available data evaluating the efficacy and safety of intrathecal (IT) administration of trastuzumab for the treatment of MC in HER2-positive breast cancer patients. This study was performed in accordance with the PRISMA guidelines. A total of 13 articles (17 patients) were eligible. The mean age of patients at IT trastuzumab administration was 48.2 years (SD 8.4, range 38-66). The mean total dose was 399.8 mg (SD 325.4, range 35-1,110 mg). IT trastuzumab alone or as part of combination therapies seemed to be safe; no serious adverse events were reported in 88.2 % of cases. In 68.8 % of cases, a significant clinical improvement was observed, while stabilization or progression of the disease was noticed in 31.2 % of cases. Cerebrospinal fluid (CSF) response was noted in 66.7 % of cases. The median overall survival was 13.5 months, whereas the median central nervous system progression-free survival (CNS-PFS) was 7.5 months. In 23.5 % of cases, IT trastuzumab was administered beyond CNS progression with a response noticed in 75 % of cases and a CNS-PFS of 9.4 months. The cumulative dose of IT trastuzumab given was 1,040 mg (SD 697.9, median 1,215, range 55-1,675). The protective effect of prior radio- or neurosurgery upon CNS-PFS was sizeable but did not reach formal statistical significance (HR 0.28, 95 % CI 0.06-1.37). Clinical improvement (HR 0.14, 95 % CI 0.02-0.91) and CSF response (HR 0.09, 95 % CI 0.01-0.89) were associated with longer CNS-PFS. IT trastuzumab administration seems to represent a safe and in some cases effective option for the treatment of HER2-positive breast cancer patients with leptomeningeal involvement. However, clinical trials are urgently needed to establish the definite role of IT trastuzumab in HER2-positive metastatic breast cancer patients with MC.
PMID: 23588955 [PubMed - as supplied by publisher]

[marvass]

Thanks very much Lani, my wife has taken over 5000mg till now.
Mario

[evlin75]

I have not totaled Susan's Herceptin mg. but she started at 20 per week in July of 2012. After about a month she went to 40 per week and the last few months 80 per week. Then progression forced the start of Depocet IT that cannot be mixed with Herceptin so the 80 is given IT every other week.
The progress has been up and down with each MRI . Overall progress better the last one but some extra tumor growth in the lower spine. The meningitis effect of the depocyt caused them to have to introduce dexamethasone each treatment and some each day to keep the inflammation under control.
The perjeta was not controlling the total body tumor problems so that was stopped and she is now on TDM1 every three weeks.
Her ambulation is difficult and she is weak from the methods used to treat her and the disease.
Radiation is being considered to zap the larger area in the lower spine. A repeat MRI will be done soon to help them make that decision.
Each persons make up is different and so the reaction to the treatments will be different, but we battle on to try to cope with the twists and turns of this disease.
My best to all who are dealing with this.
We are trying Emend now to cope with the nausea. It is also beneficial as it crosses the blood /brain barrier to help destroy tumor cells in the brain.

[dchips1]

I just received 42 mg yesterday. for number 5 It Herceptin, The first 4 were 21.

Prayers and peace to all and hor this method help others and ourselves sooner ,

Darita

[Rolepaul]

Okay, the real issue I have is that the single dose level evaluated in the 17 patients is generally lower than therapeutic levels. An initial dosing is needed at 40 mg or so to get rid of the more easily terminated cells. Starting with the higher dose results in edema and swelling of the brain. Then the dose needs to increased to 1.50 mg/kg of body weight to get rid of the cells that are more difficult to reach due to folding, scar tissue, or other reasons.
Nina has had 40 mg weekly for 8 weeks, 80 mgs weekly for 12 weeks, 100 mgs every two weeks for 26 weeks, and 100 mgs every four weeks for 16 weeks. She is alive and healthy with no signs of disease in the brain or spine 16 months after start of disease (we had a false positive on Monday, that was re-read Monday night and declared as no presence of disease by two more experience radiology people). This treatment regimen is expensive, but it has been effective in a one patient study! Nina drives her car, goes to yoga, travels to Houston by plane on her own for treatment, works on the computer, etc. She has some pain at night in the hamstrings, but that is probably due to sitting too much and not drinking enough water.
IT Pertuzumab will start clinical trials soon. That will have the higher dose studies that IT Herceptin has not had yet in a clinical trial.
I will not let this disease have my wife. I hate to lose. As Bonnie Tyler said in her song, "I need a hero"! Find your hero and get the emotional and tech knowledge support to fight the dragon.

[Rolepaul]

This article might have included Nina. She is now at 2800 mg (+/-) in total. The target effective dose after initial 40 mg dosing is 100 mg for 62kg of body weight. I am not a doctor, but this therapy should make sense to Brain and Spine oncologists who team with Breast Cancer people. CFS turnover is 500 mls per day. Blood is about the same, but CFS is 1.5 liters max, and blood is 12 liters. That is why the dose needs to be about 1/3 of the IV dosing to be effective. Having helped Nina study for her RN, being part of the development team for MAb diagnostics, and a whole lot of other education on getting things to work resulted in this therapy plan. It might not be perfect, and might be too high a dose or too frequent, but I think a little extra is not a bad thingg if death is the alternative.

[Rolepaul]

So Nina is now an 18 month survivor and a year in remission from 20-30 small nodules in her spinal nerves and three medium size brain lesions. She is at 4000 mg IT Herceptin and 38 mg IT of Topotecan in that time. She is a little less self assured, but was given only 90 days to live initially. All I can say is that Perjeta or Herceptin using IT at 1.5 mg/kg seems to work. This should give direction to the Perjeta study for leptomeingeal and brain involvement that will start at the end of the month.

[Rolepaul]

This is two years since diagnosis of LMD in the spine and four years since it was found in the brain. Nina just was evaluated and found to remain in remission. No change in the past 18 months for the MRI scans, Protein/glucose in the spinal fluid, or symptoms of disease. This is truly remarkable to think about. More studies are ongoing at the higher doses now shown to be needed for therapeutic reasons. Keep up the hope and don't give up.
Rolepaul

['lizbeth]

I think it is so amazing that Nina has had such wonderful success with the IT Herceptin. May she savor the Christmas holidays as a true miracle.

[dchips1]

Are they using both perjeta and Herceptin IT. How did Niña do with IT topotecan.

Just looking for more options for the t-8 lesion that has grown and fluid increased

Darita

[evlin75]

Darita, keep thinking positive. My daughter Susan is feeling much better now and thinking of getting a three wheeled bicycle to scoot around her neighborhood. She is a bit afraid of trying to do the two wheeled type she has as yet. She is feeling stronger and more herself the last few weeks. She had to do Depocyt once every three weeks for a while and that had bad side effects. The Herceptin was not able to do the therapy alone part of the first few weeks. Now she just gets the Herceptin 8o mg IT each week which seems to be therapeutic for her as she has lost a lot of weight. She has not had an MRI for a few weeks but she keeps feeling stronger each day.
On the whole body treatment the kadcyla was not working for her. They changed her to Abraxine and Herceptin. She gets the whole body treatment through her arm port. The only problem she seems to have right now is the enlarged clavicle lymph nodes. She will receive Nano Knife to that area next week.
No way to know about tomorrow but right now she is feeling great and looking forward to Christmas.
There is hope with the Herceptin so "keep truckin"
Ev

[Rolepaul]

So Nina gets the Topotecan (0.4 mg in 5 ml of sterile water) after they pull 18 mls from the Ommaya. She then has a three ml of the withdrawn fluid to flush the tubing, followed by 100 mg of Herceptin in 5 mls of sterile saline. This is flushed with 3 mls of the withdrawn fluid and then 2 mls of sterile saline. It takes about five minutes in total time to do this part, but 15 minutes of prep and 5 minutes of follow up. It does not hurt as they use a 28 gauge needle (think the smallest needle bore made) to go through the skin and pierce the valve on the Ommaya. They dress the area and gown as for a local surgery area. I watch them and give them advice on how to keep the working area sterile (ie do not pass hands over the top of the field, no cardboard or paper within six inches of the edge of the field, they double glove with sterile technique, etc.) The nurses think I am more picky than the training nurse! But I have a dog in this fight. There is good evidence that the Topotecan is not completely necessary, but that was the initial approved protocol that the doctor piggybacked the Herceptin on to. I repeat, this was not easy to get acceptance, but it is now getting more readily approved for patients. The doctor is willing to give Nina's treatment information to other physicians and is treating more patients.

[Rolepaul]

Perjeta is coming. I heard University of Southern California was going to be the first to get approval, but it has stumbled. I will be at an undisclosed location on January 8 to discuss this with the team from the pharm company as part of other work.

[evlin75]

Susan had Perjeta and TDM1 (kadcyla) and most all the other new medications floating about out there in chemo-land. Perjeta did not seem to work at all for her - or even the kadcyla.
But she has been dealing with this since JUNE 2003 when diagnosed with invasive ductal. Went to her hip less than two years later.
She received the traditional chemotherapy (red devil) followed by radiation in 2003. Herceptin not approved yet for newly diagnosed. Started on it after mets to bone.
2009 surgery for a large tennis ball tumor on the cerebellum - the whole brain radiation. She recovered nicely.
She has received almost all the medications out there floating about in chemo-land. Even some oral chemo that did not seem to work well.
She has tried to stay away from the taxanes and other IV type chemo.
It was April of 2012 when she was diagnosed with the lepto-meningeal carcinoma. The doctor at that time said just a few weeks prognoses. I began researching immediately and the doctor also noted the Chicago trial of IT therapy of Herceptin at the same time I found the IT possibility.
Had to go to another doctor out of the trial to get a higher dose. Hard to find a brave doctor who will go beyond current protocol.
It has been a long journey with the first ommaya getting infected. and the topecan not doing the job.
Had to switch to depocyt for a few weeks. Many bad side effects from the Depocyt those weeks with steroids necessary. But the Herceptin is now used alone and she is getting stronger. 80 mg IT seems to be holding her.
The Nano Knife is being put on hold as the
Abraxine/Herceptin combo is shrinking the clavicle tumor - now 1/4 the size after two treatments.
Susan is
feeling good and looking forward to a nice holiday.
I am glad she had the Taxanes in reserve to fall back on.
EV

[evlin75]

Correction. ... Diagnosed originally April 2003. Lepto diagnosed June 2012

EV

['lizbeth]

Evlin,

I'm so sorry that Susan is forced to deal with an aggressive, resistance cancer. It sounds like you have been very fortunate with the current treatments and that amazing doctor.

We will definitely keep her in our prayers. I hope that soon she can maintain stable with only Herceptin and have a nice break from the harsh chemotherapies.

@Paul - keep us posted on Perjeta. Do you mean it will be available as IT Perjeta?

[Rolepaul]

Ev,

I keep looking at 1.6 mg/kg of body weight as a good target dose. Hopefully Susan is about 50 kg (110 pounds) or so in weight. If not, see if they will bump the dose. Nina had truly remarkable results in about four months at that dose. She is also a little bit bad on balance, but refuses to do the three wheeled bike.

I was looking at the IT Perjeta if there is any recurrence in the brain or spine. That is the trial that was supposed to open in July of 2013. I have access to people and will find out why it did not occur around the first full week of January. I know northwestern in Chicago is doing lower dose IT Trausuzumab but is looking to bump the dose to 100 mg per week shortly. I would like to see the Perjeta dosing at the same level. It is hard to move the industry, but people do seem to listen to me a little more readily than other people.

Happy holidays for as many of the readers as possible. The industry is trying to help everyone here.

Paul

[evlin75]

Paul,
Susan is very close to the 110# weight and she is getting the Herceptin IT EVERY week. That is a total of 320 mg per month. This doctor has been great so far about our requests but so far won't budge on raising it beyond the 80.....not that we have not tried.
I too wish everyone here a great holiday season and much good luck.
Ev

[Rolepaul]

Ev,

Good deal. I am also looking at Pfizer and Mylan biosimilars to see if they would be good alternatives if Nina develops resistance to Herceptin from Genentech. I have inquiries out with their top research teams.

May this concern be gone in 2014 with documented and effective treatment for all.

Paul

[evlin75]

Herceptin goes off patent overseas in 2014 and in the US in 2019. I understand some similar products are already in the works over seas. Some good could develop from that effort.
Ev