I was recently asked by a surgical colleague to meet a patient. This 58-year-old woman had presented two years earlier with sigmoid colon cancer. Though the tumor was invasive it was negative for lymph node involvement.
As node negative (Stage II) colon cancer has uncertain benefit from post-operative adjuvant chemotherapy she decided against chemotherapy and she was observed. At 18 months, the patient suffered abdominal discomfort and was referred for a CT scan that revealed a 12 x 8 cm mass in the liver. The CEA tumor marker was rising and it was evident that she had recurrent cancer. The patient asked the surgeon to do all in his power to save her life and he called me to discuss her case.
One week later, we received a surgical biopsy for analysis and set about studying cytotoxic agents like FOLFOX combined with inhibitors of the VEGF (Vascular) and EGFR (Growth Factor) pathways to help identify the most active combinations. There are now many widely used regimens for metastatic colon carcinoma and our laboratory can examine virtually all of them.
We are particularly interested in the study of drug synergy that defines favorable drug interactions. We know that for some patients, Oxaliplatin is highly synergistic with 5-Fluorouracil. In others, Irinotecan can be synergistic. For others, the combination FOLFOXIRI offers the best chance. The standard of care for this patient would be FOLFOX plus Avastin, and it is almost certain that she would receive it in the hands of any medical oncologists in America whether university or community based.
It is the gold standard.
Her Functional Profiling Results
Our laboratory results, however, suggested something different.
The activity for this patient was profoundly enhanced when we added drugs that block the epidermal growth factor, so much so that the drug combination FOLFOXIRI combined with the epidermal growth factor inhibitor killed almost every cell even at the lowest concentrations tested.
The addition of a VEGF inhibitor proved even better. It was evident that this patient's tumor was primed for the right drugs, but I was concerned that she might not receive them. I consulted with the patient and reviewed our findings with her and her husband. She had received such dismal news preceding our meeting regarding liver recurrence that she was emotionally distressed as I explained my results.
Her husband inquired whether I had used this approach in patients like her and I said yes, that we had several very long-term survivors with this approach.
She decided to proceed with treatment.
Since our first meeting, the molecular profiles conducted upon her tumor have further supported our findings. We crafted a novel drug combination that targets each of the patient’s cancer cell’s vulnerabilities, both cytotoxic and targeted. Although there is no certainly that any given patient will achieve response, in our experience colon cancer patients with this profile do the best, many very durably. While no one wants the diagnosis of cancer, high volume, metastatic, recurrent colon cancer that replaces much the liver leaves very little to be optimistic about. Despite the gravity of this patient’s presentation, her laboratory results offer real hope. As an otherwise healthy, vigorous woman she should tolerate the treatments well. Based upon our foreknowledge of her drug sensitivity, we can adjust her doses to provide activity without undue toxicity. If we can’t choose our battles at least we can choose the tools we use to fight them. I am optimistic that this patient will respond and I will update this blog with a progress report.
While there are no good colon cancers, there are some patients who have very treatable ones. Our job is to find out who they are before we treat them.
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
