Today I faced one of the toughest decisions of my career. Oddly, it didn't come in my workplace and it doesn't even involve one of my patients.
A little over a year ago, my best friend's Mom, D, was diagnosed with ovarian cancer. Following debulking surgery, she was treated with first-line therapy using Taxol plus intraperitoneal Taxol/Cisplatin. By some miracle, she was deemed cancer-free at the end of last year.
Fast forward to six weeks ago when her CA-125 returned elevated at 86. The CT scan showed a small, indeterminate area that the doctors elected to observe for a short time. She had her tumor marker re-checked this week and sadly it was 646. As I already knew before the CTs confirmed, her cancer was back. At the follow-up visit today, the doctor told her the cancer looked like the "glaze on a donut," describing the peritoneal carcinomatosis coating her abdominal wall.
In D's case, her disease recurred greater than six months after she completed treatment, so she is considered "platinum-sensitive" rather than "platinum-resistant." Her doctor presented her with four treatment options. My best friend is now asking me to choose the best one.
- Carboplatin + Gemzar + Avastin -- all agents given day one, Gemzar alone day eight
- Carboplatin + Doxil once every 28 days
- Carboplatin + Taxol once every 21 days
- Carboplatin + Taxotere once every 21 days
I must try to look at this objectively and give sound advice as an oncology clinician. After all, that's why she's coming to me, right? But then again, this is personal. I love this family like my own. This woman, like so many others, is middle-aged, was otherwise healthy before this began, and has so much to live for.
The leading authority for treatment decisions is the National Comprehensive Cancer Network (NCCN), an alliance of 21 leading cancer centers that set the standard by which we all practice in community-based oncology settings. The NCCN guidelines for recurrent disease recommend a clinical trial, second-line therapy, or supportive care.
Option one is a clinical trial utilizing Carboplatin plus Gemzar (an accepted second-line therapy) with the addition of Avastin. Avastin is a vascular endothelial growth factor (VEGF) inhibitor, blocking the ability of cancer cells to perform angiogenesis. Avastin has shown progression-free survival (PFS) benefit in other clinical trials for ovarian cancer, but no improvement in overall survival (OS) (NCCN, 2012).
As we know, Avastin has proven effective in metastatic colorectal cancer and advanced non-small cell lung cancer and thus, from a clinician standpoint, this regimen has appeal. The cons to this treatment are the regimen being every two out of three weeks, and myelosuppression, both because of Gemzar's effect on the blood counts and her prior history of chemotherapy.
Option two offers Carboplatin plus Doxil. According to the NCCN, this regimen has also shown PFS benefit, but again no OS benefit. The major pro to this option is that it takes place every 28 days. The cons are increased risk of nausea, allergic reaction, and hand/foot syndrome.
Options three and four, in my mind, aren't much different. As oncology professionals, we all know the subtle differences between Taxol and Taxotere, but in the end, taxane drugs have the potential for two big side effects -- allergic reaction and neuropathy. D struggled with neuropathy during initial therapy, and thus repeating a taxane drug would only worsen this toxicity.
Another thing that bothers me is she already had treatment involving a platinum-based therapy plus a taxane. Thus, these final two options do not differ greatly from what she originally received. Because she is not considered "platinum-resistant," however, these are still approved options.
In the end, I recommended the clinical trial. Despite the more grueling regimen in terms of time spent in the office, overall the toxicity profile seems better and the treatment seems to give her the best odds. A clinical trial also offers the chance for D to possibly save another woman down the road from this life-threatening illness. This is something I believe would mean a lot to her.
So what would you have chosen? Would you have even given your opinion in such a personal situation?
National Comprehensive Center Network. (2012). NCCN Clinical Practice Guidelines in Oncology. Retrieved from http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#ovarian.