A 39-year-old woman with a one year history of rectal bleeding attributed to hemorrhoids — that preceded and continued throughout pregnancy — initially presented postpartum with continued hematochezia. Work up shows a large fungating mass in the rectum and CT evidence of four bilobar liver metastases. She was treated in the community with immediate resection of the rectal cancer including permanent colostomy, and wedge resection of all liver metastases. She presented two days postop to a tertiary center for additional evaluation. Upon recovery from surgery, she completed 12 cycles of FOLFOX and bevacizumab, completing the first cycle of FOLFOX alone and the subsequent cycles with the addition of bevacizumab. Twelve months after initial surgery, a CT scan showed three nodules in the left lung. She subsequently experienced two episodes of recurrent disease confined to her lungs, both treated with resection and further systemic therapy. Four years after diagnosis, she continues on intermittent systemic therapy for persistent small volume measurable disease.
Case Discussion:
This was a 39-year-old woman with a long history of rectal bleeding that continued throughout pregnancy and was attributed to hemorrhoids, initially present postpartum. Her workup revealed a large fungating mass in the rectum and CT showed four bilobar liver metastases. At the time of surgery, no extrahepatic disease was found, and she underwent resection of the rectal cancer with a permanent colostomy and wedge resection of liver metastases. She presented two days postop. Although controversial considering her young age, the surgical team decided to proceed with resection of both the rectal cancer and liver metastases. The patient had never seen a medical oncologist or radiation oncologist prior to surgery.
If I had seen this patient prior to surgery, I would have at least discussed the possibility of preoperative treatment. A Swedish approach uses accelerated radiation therapy without chemotherapy to the primary tumor over five days. The other consideration, given that she had multiple areas of the liver involved, would have been to administer three months of chemotherapy initially to establish control of the disease, and then perform the resection with additional chemotherapy administered afterward.
Data on initial chemotherapy for potentially resectable liver metastases are all retrospective. The data from Rene Adam suggest that patients with progressive disease during chemotherapy who are still able to undergo a resection don’t fare as well, so that was part of my concern. The other concern was that if she had complications from surgery, it could be six to eight weeks before she could receive chemotherapy for potential micrometastatic disease elsewhere in the liver, and at that point, she might already have new growth of metastatic disease. So eradicating some of the micrometastatic disease up front might help increase the chances of controlling her disease after the surgery.
Fortunately, she recovered quickly from the surgery and went on to receive 12 cycles of FOLFOX and bevacizumab. We decided to use bevacizumab because the data suggested that it enhances chemotherapy in metastatic disease, so it seemed appropriate to use it in combination. If the K-ras data were available back then, I would have checked her tumor for K-ras status and used cetuximab if her tumor was wild type. The patient fared pretty well except for cytopenias, which were reasonably well controlled by removing the bolus 5-FU, and most cycles of chemotherapy remained on schedule. Despite receiving 12 cycles of FOLFOX, she had little neuropathy at the conclusion of the chemotherapy and tolerated it amazingly well.
Twelve months after the initial surgery and approximately six months after completing postoperative chemotherapy, a CT scan showed three lung nodules in the left lung. Based on the retrospective data supporting the resection of lung metastases, similar to liver metastases, we decided to resect the lung nodules. Two were removed from the left lower lobe and one was removed from the left upper lobe.
Because I was concerned that the risk for recurrent disease was still high, she then received a combination of FOLFIRI and bevacizumab. We planned to administer 12 cycles, but treatment was discontinued after six cycles because she had a fair amount of nausea with the FOLFIRI. Since she had disease progression on the prior regimen of FOLFOX, no additional chemotherapy was administered.
If the patient had been in her late fifties instead of late thirties and had this same three lung nodule recurrence, I would have still used the same treatment, considering the fairly quick recurrence. If the lung nodules appeared two years after she received chemotherapy, I would have been more in favor of observing the patient and using chemotherapy at a time of further recurrent disease.
Six months after the left lung surgery, she had evidence of bilateral lung nodules on a CT scan, five in the right and one in the left. After 10 cycles of FOLFOX and cetuximab, there was marked shrinkage of the nodules in the right lung, while the left lung nodule remained stable. Because of her young age, she underwent resection of the right lung nodules. We decided to watch the left lung nodule, because it hadn’t changed and the thought was that it might be benign (the nodule was too deep in the lung to biopsy).
The patient fared well for 14 months, until her CEA began rising. A PET/CT scan revealed a new right lung nodule that in the area of a prior resection, a possible recurrence in her liver, and more concerning, an enlarging periaortic lymph node. Since she had had a good response to FOLFOX and cetuximab, it was restarted, but unfortunately she developed an allergic reaction to the oxaliplatin, and we had to discontinue the oxaliplatin because she became flushed and hypotensive.
She was then treated with capecitabine and cetuximab. After five or six cycles, the PET scan findings and her CEA normalized. She has been on the two-drug regimen continuously for the last eight months. The enlarged lymph node shrank, and no longer appears on the scan, and there is nothing showing in the liver.
Few data exist on the use of capecitabine with cetuximab. The approach is mainly stop-and-go and simply continuing either cetuximab or bevacizumab into the maintenance setting, but there are not a lot of prospective data on capecitabine and cetuximab.
