"Magic happened!" A husband tells the story of his wife’s success with a treatment for HER2+ leptomeningeal and brain metastases

UPDATE, December 2016

Paul reports that Nina is still doing very well and in full remission.  He has helped many other patients gain access to the treatment his wife had. If you or someone you love has been diagnosed with HER2+ leptomeningeal metastases, please write us for Paul's contact information.

UPDATE, March 2015

Nina had her third set of good MRI scans. It shows that two potential lesions that were in question are still probably just radiation scars. Her health is incredible and allows me to take travel jobs, such as the one I am on now in Omaha. Spread the word as almost everyone that has had treatment at the 1.5 mg/kg to 1.8 mg/kg level are doing great. Hopefully others will get treated with the same success.

UPDATE, December 2014

So the follow up scans this week show that the October MRI and CT scans were not a fluke.  Nina is in full remission of Her+ Breast Cancer in her brain, spine, and the rest of her body.  The first time MD Anderson has ever seen it, and now they are putting more patients on this protocol.  December 15, 2011 we were told about three lesions in the brain and 20 to 30 at the base of the spine. We were told that 3 to 6 months of life were the standard.  On this visit, we were told that Nina is so far off the scale of normal that there is no explanation.  My explanation is gaining knowledge, using the knowledge to get the best care possible, and have a great drive.  It would be interesting to know how many others have had complete remission with Brain and spine involvement.  At least six ongoing cases with similar protocol and all are alive, four after two years.  I think the HER+ Brain Mets group needs to push hard to look at this.  A couple of relapses occurred at lower dosing, but so far so good at 100 mg per treatment per week.  Three more women were enrolled within the past four months.  Keep spreading the word that this is not a nice place to go, but there now appears to be a way to move on successfully. 

UPDATE, October 2014

On November 2, 2009, Nina was found to have a 6 cm diameter by 1 cm thick lesion on her brain.  They excised it with surgery, Gamma knife Radiation, and then went to Xeloda/Tykerb to try and get it under control.  December 15, 2011 three lesions that had been there for a few months were sticking around, but an MRI scan of her spine showed 20 to 30 small lesions at the small of her back.  January 12, 2012, the doctors at MD Anderson gave her the first 40 mg dose of Intrathecal Herceptin through an Ommaya reservoir on a weekly basis, boosted to 80 mg Herceptin/0.4 mg Topotecan IT on Feb 2 2012.  They added systemic Herceptin and Navelbine for a while.  The amount of Herceptin was slowly increased to 100 mg per every four weeks by October 2012.  The MRI scans showed a slight change in uptake and size through September 2014.  Maybe disease, maybe radiation residuals, maybe Herceptin degradation.  August 1, 2014 they found that a subcarinal lesion had gone from 1.4 by 1.2 in April to 1.8 by 1.4 in August.  Systemic treatment was moved from Herceptin only to TDM-1.  After three treatments, the subcarinal node is back to 0.8 cm (ie normal size) but the interesting thing is that the brain lesion is 1/4 its previous size and the signal is significantly less.  This indicates that the brain/spine disease has probably gone into true remission. 

You might say Nina beat the odds and has laid a potential path forward for investigators.  I hope this helps with getting help for other patients.

Here is their whole story, recounted by Paul in 2012:

In July 2005, my wife was diagnosed at age 45 with HER2-positive, ER-negative, PR-negative breast cancer.  The tumor in her left breast was 6 cm. in circumference, with 4 of 20 lymph nodes positive for cancer.  She was given a course of chemotherapy (Adriamycin/Cytoxan, followed by Taxol), 30 rounds of radiation to the left breast, and nine months of Herceptin.  A three year period of follow-up included a breast exam, tumor markers, and a once-a-year PET scan. 

After three years, it became difficult to get a PET scan because the oncologist felt that the risk of recurrence was small.  My wife completed her BS in Nursing at a major university, and began work as an operating room nurse.  There were no signs of any disease, and we started to believe that her cancer would not come back.

 Then in June 2009, my wife experienced some headaches and stiffness in her neck.  Over-the-counter pain relievers didn’t help.  In October, a PET scan and tumor markers were done.  On November 1, an MRI revealed a 5 cm. x 1 cm. tumor on the top back surface of her brain.  Although this oncologist was associated with a well -known university hospital, we decided to contact and interview additional cancer centers to determine which facility best suited our needs. 

On November 19, the tumor was surgically excised.  Two weeks later she had Gamma Knife radiation on two areas of the tumor.  She started taking Xeloda and Tykerb, in a two week on and one week off Xeloda regimen, for a period of 18 weeks.  Her hand-foot syndrome was treated with a henna and lemon juice paste every two to three days for 45 minutes.  Her hands were covered with Bag Balm or udder cream, with cloth gloves used at night. 

The following year, in November 2010, an MRI revealed three tumors on the meninges of her brain.  Gamma Knife was used again and Xeloda was restarted.  Additional radiation treatment of the brain was done in March and April of 2011.  MRI and PET scans showed generally stable disease until in December, 2011, when a PET scan showed potential spinal area involvement, confirmed with spinal MRIs.  There were 20-25 satellite tumors clustered from her middle back to her waist.

The news was devastating.  My wife and I met with the doctors and were told that the situation was very dire and that end-of-life decisions should be made.  Since I worked in the pharmaceutical industry, I was able to determine a potential treatment method that had showed promise.  The research literature mentioned fewer than 15 patients who had been treated with intrathecal Herceptin (IT Herceptin).   Because there was so little evidence that intrathecal Herceptin might help, we had to go through intense negotiation about a treatment plan, with additional chemotherapy requested by the physicians.  The plan was finally agreed to under a "compassionate use" protocol.  Ten radiation treatments were done to the spine to initiate treatment of the spinal tumors.  Under general anesthesia, an Ommaya reservoir was installed at the hairline on the right side of my wife's forehead.  Because of how frequently the medication would be delivered, this approach was preferred over the use of a spinal push.

The dosing regimen that was used with my wife was based on the dosage seen in Germany and Japan. We were able to get the neuro-oncologist to agree to 0.6 mg/kg (or 40 mg for my 60 kg wife) versus the 10 mg starting dosage done at the approved Northwestern trial. My wife's dose was boosted to the target of 80 mg after four initial treatments. She has remained at this level for the remainder of the treatment.  1.2 mg/kg is consistent with the 100 mg dose for the German patient based on the weight of that patient.  Higher doses of Intrathecal Herceptin appear to be necessary versus the IV dosage regimen due to the higher turnover of CFS (cerebrospinal fluid) versus blood and plasma. Radio-labeled Herceptin studies show that CFS residence time is one fifth the whole body turnover. While the patients treated at the higher dose do not appear to have negative effects versus the lower dose patients, the initial dose appears to have significant potential for nausea and vomiting 24 to 72 hours after the first IT treatment. This may be due to cancer cells being killed and releasing their toxins into the brain cavity. Improvements in MRI scans, CFS protein and glucose, and tumor markers are seen within four weeks at this higher dosage. 

Magic happened!  The first dose of 40 mg of Intrathecal Herceptin was given on January 12, 2012.  When my wife showed no ill effects, three additional weekly treatments were done.  An MRI on February 2, 2012 showed that progression of the disease had stopped.  It was determined that 0.400 mg of Topotecan would be added to the intrathecal treatment as well, with a twice per week regimen.  This treatment is a syringe addition of solution into the reservoir via a topical needle.  Total treatment time for both medications is less than ten minutes.

Two weeks later additional systemic Herceptin and Navelbine was added to reduce the risk of the tumors spreading to other parts of her body.  Abnormal cells had been seen in the blood, and tumor markers had become elevated.  The IT treatments occurred on Mondays and Thursdays with the intravenous treatments the following day, on Fridays. The intravenous treatment was initiated with a 225 mg per week dose of Herceptin and 42 mg of Navelbine.  After four weeks, the IV Herceptin was reduced to 125 mg. The combined IT and IV treatments led to a significant reduction in MRI contrast agent uptake for both the spine and brain.  In addition, no abnormal cells were found in the fluid removed from the spinal tap or Ommaya, and none were seen in a blood sample.  This news was outstanding.  The decision was made to reduce the Topotecan to once per week, and the Navelbine was reduced to three weeks on and one week off.  After the reduced treatment was initiated, her white blood cell count showed a drop, so Neupogen was added to the regimen on day 1 and 2 after the Navelbine IV treatment.

Evaluation of the MRI was performed after four weeks and then again on May 30 and 31 for the spine and brain.  A PET scan was done on June 1, 2012.  The results of these scans showed only background levels that were consistent with normal tissue.  There was no longer any evidence of the cancer.  The IT Herceptin and Navelbine have been reduced to once every two weeks, with the IV Herceptin and Navelbine scheduled to be reduced to once every two weeks.  The goal is to have a once per month treatment of IT Herceptin and IV Herceptin to allow my wife a near normal life.  She will have MRIs performed every two months initially, with a goal on moving to six to twelve months in the future.

We are hopeful that a full scale clinical trial of high-dose intrathecal Herceptin will be conducted, with multiple sites, to allow more women to be given a chance to live.  This treatment was novel due to the higher dose of Herceptin than had been previously thought to be needed.  The need for a higher effective dose might be due to the significantly higher turnover of the cerebral spinal fluid versus the blood supply.  It is well documented that Herceptin cannot pass through the blood-brain barrier, and Xeloda/Tykerb are not effective in the long term for brain or leptomeningeal involvement of HER2-positive tumors.

My wife's treatment inspired another husband in Europe to have the same treatment done for his wife who was in similar straits. Their efforts to get this done in the US were not successful. They returned to their country, where the doctor agreed to repeat our initial work, and went up to 90 mg per weekly dose. His wife's results were as amazing as my wife's were. This couple now is working to get the same treatment available throughout Europe. It is clear that this treatment is not easily achieved in either the US or Europe in mid-2012, we have continuous contact with doctors to get this work out there to others. I know of several women who are investigating compassionate care protocols with this same treatment. It is clear that there are options for those with HER2-positive lesions in the brain and/or spine. Hope, or should I say treatment, is out there for even this form of the disease.