Dr. Nagourney's Blog

Stage 4 Gastroesophageal Cancer Patient Responds to Novel Cocktail

By Robert A. Nagourney, MD

On June 5, 2019, I received a telephone call from Des Moines, Iowa from a 60-year-old gentleman who had presented to medical attention with an adenocarcinoma of the gastroesophageal junction.

Having the capacity to seek medical opinions from experts around the US, he traveled to Texas to one of the leading cancer centers. His disease was too advanced for surgery so he began a drug combination known as FOLFOX, one that is widely used in gastrointestinal cancer. He remained on treatment until a follow up scan in May revealed that the disease had progressed in the chest and lymph nodes in the neck.

Although he was at one of the most famous institutions in the country, their second line recommendation, not unlike their first line therapy, was straight out of the textbook, the two-drug combination of Ramucirumab plus Paclitaxel. As he considered his situation, he contacted me to discuss his clinical options.

I explained that he had received appropriate therapy in Texas, but that he had simply not responded. As FOLFOX therapy carries a response rate of 30-50% for his cancer, his failure to respond wasn’t out of the ordinary for this disease.

The recommended 2nd line therapy, though reasonable, was not different from treatments that he might be offered in Des Moines, Sheboygan or Hackensack, New Jersey. Though there was nothing wrong with the second line choice, there wasn’t anything particularly right about it either.

His Functional Profiling Results

The patient and his wife decided to travel to California where we conducted a lymph node biopsy.

The surgical procedure led to a complication that required weeks of recovery but when the results of the biopsy were complete, they revealed an unexpected degree of activity for drugs that inhibit a cellular protein known as the epidermal growth factor receptor (EGFR) suggesting that this patient’s tumor might be using this pathway to grow and survive.

To further investigate, we requested that the results of his tumor genomic analyses that examined his cells for DNA mutations be sent to us from Texas.

While the gene test did find several mutations including FANCD and TP53, there were no activating mutations in EGFR.

As I examined the findings more closely however, I found that the cells had EGFR amplifications, indicating that the cancer cells were manufacturing more of the EGFR protein and using this excess production to their advantage. This, I reasoned, might explain why the EGFR inhibitors looked so active.

We treat EGFR mutations with drugs known as tyrosine kinase inhibitors like Erlotinib and target the EGFR protein on the cell surface with the antibodies like Cetuximab. It is sometimes more difficult to interpret EGFR amplifications but in this patient’s case the EGFR amplification appeared to be an important driver of his cancer.

Recommending a Novel Cocktail

I pieced together a combination of carboplatin, paclitaxel, and the anti-EGFR antibody Cetuximab that fit very closely with the findings in the laboratory study.

Now we needed to find someone who would treat the patient according to our findings. It appeared unlikely that he could return to Texas and equally uncertain whether his physicians in the Des Moines would apply our suggestions.

I decided to contact my colleague Dr. Keith Block in Skokie, outside of Chicago.

Although Des Moines and Chicago are 300 miles apart, that’s a much shorter trip than the 1600 miles that separate Des Moines from LA. Dr. Block was only too happy to help.

Patient Response - Hitting the Target

Six weeks later, I was contacted by Dr. Block’s associate.

She was immensely impressed by the patient's dramatic response.

He had begun to eat, the tumor had diminished markedly on PET and CT scan, and he had tolerated the treatment well but did complain of some neuropathy as a side effect.

She said that I had clearly saved the patient's life.

As I examined the patient's outcome, I realized that the combination was relatively simple, readily available, generally well tolerated, and something that absolutely no other institution would have recommended. There was nothing particularly difficult about giving the treatment; the real difficulty was identifying it.

Update on Patient's Progress

I had occasion to speak with the patient and his wife a few days ago.

He’s delighted with his progress, but with symptoms of neuropathy we decided to modify the regimen to substitute Paclitaxel with a less neurotoxic drug from among the many other agents that we had tested.

Lessons Learned and Hits the News

The patient's outcome is instructive.

First, we were able to identify a smart and relatively well-tolerated, effective treatment.

Second, we were able to work with colleagues in Chicago, making the patient's life easier.

Third, the patient's good outcome was so impressive that it is the subject of an ABC News story that aired November 5th, 2019. https://www.weareiowa.com/news/local-news/changing-the-odds-iowa-man-benefits-from-customized-cancer-treatment/

Conclusion

This patient represents one more example of a good outcome that could easily have been missed.

While patients travel to the major centers in the US to receive care, many of these centers offer standard therapies. As physicians we must use every resource at our disposal to identify active treatments.

I am pleased that this patient asked for my assistance, pleased to have good collaborators in the oncology community and above all else pleased with his excellent outcome.

As always, I appreciate your thoughts and comments.

 

Dr. Robert Nagourney, has been internationally recognized as a pioneer in cancer research and personalized cancer treatment for over 20 years.  He is a TEDx speaker, author of the book Outliving Cancer, a practicing oncologist and triple board certified in Internal Medicine, Medical Oncology and Hematology helping cancer patients from around the world at his Nagourney Cancer Institute in Long Beach, California.  For more info go to NagourneyCancerInstitute.com