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The surprise of hearing ‘I’m back!’
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“Surprise, I’m back. See, I’m still alive.”
That was the greeting I got from my patient who upon returning from her winter stay in Florida literally danced into my New Jersey office in June 2007. When I last saw her in November 2006, I started her on panitumumab (Vectibix, Amgen), as a last ditch effort to slow and/or reverse the progression of her metastatic colon cancer. I was delighted to see that she had responded to the treatment.
My patient first developed colon cancer in June 2004. At that time, she received 5-FU (Adrucil) and leucovorin (folinic acid) as adjuvant therapy. She was found to have liver metastasis in October 2004 and was started on 5-FU, leucovorin, oxaliplatin (Eloxatin, Sanofi Aventis), and bevacizumab (Avastin, Genentech), ie, the FOLFOX combination. She improved, but in October 2005 because of progressive disease, I began irinotecan (Camptosar, Pfizer), 5-FU, and leucovorin. During this period, she was also treated with erbitux (Cetuximab, Imclone). She did well for another year, but showed progression in the fall of 2006, which is when I started her on panitumumab. This was successful until the fall of 2008, at which time I stopped the panitumumab, and started her on a short course of erbitux and bevacizumab. This was not successful. She left for Florida with a note from me for her Florida oncologist, suggesting that he consider returning to either the FOLFOX combination or consider XELOX — a combination of capecitabine (Xeloda, HLR) and oxaliplatin — since she had not had oxaliplatin since 2004.
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As I write this in January 2009, my patient, who is back in Florida for the winter, has been under treatment for metastatic colon cancer for the past 51 months. Although the patient will not be cured of her condition, the palliation of her disease has, in my opinion, been significant. She continues to function and participate in her family’s events. This patient’s course is not uncommon in 2009. When I started to practice in 1974, on occasion we would use 5-FU, which was developed in 1958, as adjuvant therapy for colon cancer, although at that time there was no scientific evidence to justify it.
We also used 5-FU for metastatic colon cancer, but saw only rare responses to the drug. What came along next was the use of leucovorin to potentiate the effect of 5-FU. With this combination, we actually saw an occasionally significant response. The NCI some time later published guidelines, giving its approval for 5-FU/leucovorin adjuvant therapy of colon cancer. The significant benefit in preventing relapse was quantitated and was quickly adopted by the entire oncologic community.
Irinotecan was approved in 1996 and oxaliplatin followed in 2002. We are now in an era that includes the biologic drugs erbitux (2004), bevacizumab (2004) and panitumumab (2007). We will all soon be testing for KRAS gene mutations, which will help identify patients unlikely to respond to the targeted EGFR inhibitors erbitux and panitumumab. Conversely, the absence of KRAS mutations will need to be demonstrated before starting EGFR inhibitors. Other approaches that have only relatively recently entered as common treatments include hepatic resection of metastasis, tumor ablation by bland embolization or chemo-embolization, and gamma knife radiation therapy.
All of these therapies have changed the treatment strategies of both early and late colon cancer. My junior associates, who roll these new treatments off the tip of their tongues as if they have been standards for decades, may fail to appreciate just how new many of these concepts and treatments actually are. We have a lot to thank the researchers of the last several decades for. They have enabled us to cure more patients than ever before, and to help those with metastatic disease.
The next quantum leap in the field of colon cancer may come with the use of a stool DNA test to diagnose occult colon cancer. At present, it only finds 50% of those cancers seen on colonoscopy, is expensive, and involves collection of an entire stool sample. However in my opinion, it holds great promise. Once again, there seems to be never a dull moment in the field of hematology/oncology.
Arthur Topilow, MD, is in private practice at Atlantic Hematology & Oncology in Manasquan, N.J.
For more information:
- Imperiale T, Ransohoff D, et al. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 2004;351:2704-2714.