With the rapid rise of cancer, medical oncologists sometimes find themselves treating family members, friends or neighbors. In 2008, the mother of one of my son's classmates presented with locally advanced breast cancer. We treated her successfully, achieving a complete and durable remission. After 5 years with no evidence of disease she returned to her internal medicine physicians for regular follow ups. Almost 10 years later to the day, I received a call from the patient stating that she had abdominal discomfort. I scheduled an appointment to see her. She looked well, but a bit pale. Her hemoglobin was a little low at 9.9 and I scheduled an appointment with a gastroenterologist to rule out an ulcer. The following day, her husband called to say that she was in excruciating pain. She was seen at an ER and admitted. Her hemoglobin had fallen from 9.9 to 6.9 (the equivalent of 3 units of blood) in one day. I transferred her to my hospital for a work up. It was then that things went from bad to worse.
Stage 4 Pancreatic Cancer?
The CT scan revealed a large mass in the tail of the pancreas that had invaded into the spleen. There was extensive abdominal spread (carcinomatosis), ascites (fluid) and a large pleural effusion (fluid) in the left lung.
The surface of the liver had accumulated several units of blood, pushing up the right diaphragm affecting her breathing and she had developed hydronephrosis (kidney blockage) of the left.
This didn’t seem to be related to her breast cancer of 10 years earlier. There had to be a new diagnosis and that appeared to be pancreatic cancer. I consulted surgery and gastroenterology.
Her condition deteriorated requiring transfer to the intensive care unit. With breathing compromised from the pleural fluid and elevated right diaphragm it was almost impossible for her to breathe.
We removed fluid from the right lung and adjusted her medications to address her almost unbearable abdominal pain.
The gastroenterologist passed a needle through the stomach into the pancreas confirming a pancreatic adenocarcinoma.
The tumor marker CA 19.9 was 2324 (0 to 30). The patient became confused and her blood pressure became almost uncontrollable due to the pain.
Do We Keep Fighting?
She was barely oxygenating. It was grim.
How could this be? I had known this patient for years. She had been healthy and well. How could things change so quickly? Was it wrong for us to continue to support her? Was I doing a disservice to her family by clinging to the hope that she could get better? Her brother a Physician’s Assistant from New Mexico arrived. We had many discussions regarding her care. The family wanted to continue and so did I.
The Battle is Joined
We performed additional thoracentesis. More air space meant more oxygen and more oxygen meant easier breathing.
The pain came under control and she began to stabilize. I pondered the presentation. This was not the breast cancer from her early 40s and at 53 she certainly shouldn’t have two aggressive cancers. There had to be an explanation. When her breast cancer was diagnosed gene profiling was not routine but confronting a new second cancer I felt sure that there had to be underlying reason. I then did something that I had never done before.
Looking for Clues
I requested an emergency consultation with our Cancer Risk and Prevention Group. They dispatched two staffers, who conducted a blood genomic profile sent right from the ICU. I believe this was a first for the hospital. I awaited the results wondering whether this might be a BRCA mutation. The result: Ataxia Telangiectasia Mutation (ATM). This DNA repair gene, can cause cancer at a young age and is associated with both breast and pancreas cancers.
Where Have I Seen This Before?
I was reminded of paper I had co-written with UCLA years earlier on ATM. We had studied the drug response profiles for patients with a rare form of leukemia that carries ATM. These patients were uniquely sensitive to a combination of drugs that work by damaging DNA and then inhibiting its repair. For these patients the combination of Cytoxan plus 2-CDA provided durable remissions. Based on my knowledge of ATM, I pondered the options for a patient with pancreatic cancer. Clearly, I couldn’t use a leukemia drug combination, but I could apply the same principle, namely DNA damage followed by and DNA repair inhibition. I forged a drug regimen and began treatment immediately.
Her Treatment Results
With just two doses, one week apart, her condition rapidly improved. With each passing day the pain improved, her breathing improved and the indwelling lung catheter drainage diminished. As her oxygen requirements improved and blood pressure normalized, she began to eat. By the fifth week of hospitalization and her second dose of chemotherapy I stopped by to see the patient the morning before her scheduled discharge. There I found a young woman in the room next to the patient who was wrapped in a plastic hair salon gown. She was having her hair done by her stylist in time for her discharge. It was another first. After discharge we’ve continued the chemotherapy and were able to remove the chest tube. Her tumor markers continue to fall from over 4000 to 500.
Remembering that a scant few weeks earlier the patient was in the ICU, it seems hard to believe how well she’s done, a function of her receiving a treatment that was exactly right for her. We now realize that cancers respond to chemotherapy based on their unique makeup. Not unlike hormonal agents for estrogen positive breast cancers, the ATM and BRCA genes are DNA repair frailties. Radiation, platinum and alkylating agents selectively affect DNA repair. This ATM pancreas cancer behaved just like my ATM leukemia patients reported years earlier.
Her cancer has an Achilles heel and the treatment combination was the “poison arrow” she needed.
I am so pleased with her progress and feel confident that there are many treatment options. Recognizing this cancer's specific vulnerabilities, there will be other classes of drugs both cytotoxic and targeted that we can consider. Most gratifying was the strength that she and her family showed and our perseverance that made it possible to get through this particularly dark period to arrive at her current state of remarkable well-being.
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