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Metastatic colon cancer after 8 years of continous chemotherapy treatment

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Short summary

A 72 years old female that 8 years ago was diagnosed with adenocarcinoma of the sigma with liver metastasis.

She underwent sigmoidectomy and was then treated with chemotherapy, with substantial regression of the liver metastasis.
9 months after the begininig of the chemotherapy she underwent surgical excision of some of the liver metastasis and radio-frequency ablation of additional metastasis. During the surgical procedure, a catheter was implanted in the hepatic artery. Following surgery, she received systemic chemotherapy combined with local intra arterial chemotherapy.
During follow-up, progression of the liver metastasis was noted and chemotherapy treatment was repeated.

3 years after the diagnosis, the patient underwent partial hepatectomy and removal of the remaining liver metastasis. Pathological examination of the excised specimens showed only fibrosis, without histological evidence of malignancy.

During the last 5 years the patient was diagnosed 4 times with recurrence and recieved various chemotherapy protocols, as described below, with partial remission up until the last 2 months where elevated CEA (315) and PET-CT demonstrated progression of her disease.

Re-treatment with XELODA was administered but soon withheld due to 3rd level toxicity.

Patient's questions

The patient had received almost continuous oncologic treatments for the last 8 years , including all standard therapies. What are the additional treatment options for the patient?

Medical Background

A 72 years old female.
8 years ago the patient was diagnosed with adenocarcinoma of the sigma with liver metastasis. She underwent sigmoidectomy and was then treated with chemotherapy under the FOLFIRI protocol, with substantial regression of the liver metastasis.
9 months after the begininig of the chemotherapy she underwent surgical excision of some of the liver metastasis and radio-frequency ablation of additional metastasis. During the surgical procedure, a catheter was implanted in the hepatic artery.
Following surgery, she received systemic chemotherapy under the FORFOLI protocol, combined with local intra arterial chemotherapy. An half a year after the chemotherpy the treatmentet was halted on for technical reasons.
During follow-up, progression of the liver metastasis was noted and treatment with FOLFOX and AVASTIN was administered one year after the ending of the previous chemotherapy cycle .

3 years after the diagnosis, the patient underwent partial hepatectomy and removal of the remaining liver metastasis. Pathological examination of the excised specimens showed only fibrosis, without histological evidence of malignancy.
8 months later, CEA levels were elevated and PET-CT demonstrated liver metastasis progression. Treatment with OXYPLATIN was initiated but soon withheld due to severe allergic reaction. Eventually she was treated with DEGRAMON and ERBITUX which was halted later to her request.

1.5 years later, CEA elevated to 70 and CT demonstrated enlargement of a liver metastasis. Treatment with XELODA was initiated with stabilization of her disease, up until 10 months later, where further progression was noted by elevation of CEA levels to 140 and enlargement of liver metastasis by PET-CT.
3 months later Re-treatment with FOLFIRI was initiated with stabilization of her disease for almost one year, where further progression was noted by PET-CT.

An year and a half later, treatment with Irinotecan and Erbitux was initiated with partial remission up until the last 2 months where elevated CEA (315) and PET-CT demonstrated progression of her disease.
Re-treatment with XELODA was administered but soon withheld due to 3rd level toxicity.
 

Medical opinion

The patient is a 72 year old female with history of metastatic colorectal cancer for past 8 years on continuous chemotherapy with some treatment break, now with progressive disease after all standard treatments.
This consult was based on the records provided only. No radiographs or pathology were reviewed at our center.
To begin, based on the summary of the history provided, I believe this patient has been managed very appropriately over the years. She has had the appropriate level of aggressiveness balanced with quality of life considerations. There are 7 approved drugs in 5 classes for metastatic colorectal cancer. Unfortunately, there are a growing number of patients that eventually exhaust these options and have no other standard therapies.

At this point, I would discuss with the patient 2 options.
-First would be best supportive care only. The advantage of this option would be maximizing quality of life without risking toxicities of further treatment. Further treatment would be a clinical trial with agents without definitive data yet to know if the agent would change the natural history of this type of cancer and thus the risk of a trial medication is potential toxicity where it is possible there won’t be efficacy in any patient, let alone this patient.

-Second option would be a clinical trial. I would group trials for this patient in 2 forms:
1. First would be a trial specific to colorectal cancer. Those trials may be specific to colorectal cancer because early data is suggestive of potential benefit in a limited number of colorectal cancer patients and thus the drug is being tried in a larger population of colorectal cancer. Or it may be a drug that is being tested in colorectal cancer because preclinical data are supportive for this disease type but there are no human data yet that the preclinical data will translate to humans.
2. Second type of trial would be a phase I trial for an experimental agent that is being tested in many cancer types and the goal of the trial is to determine tolerance of the drug as well as potential tumor subtypes that may benefit.

One could look on www.clinicaltrials.gov for options elsewhere though I would state I don’t know of a trial specific to colorectal cancer that I have knowledge is definitely promising – but we would not know until it is tested. We do have an active phase I program run by a different group of physicians. At any given time, they have about 10-15 active phase I trials – some agents may make more sense for colorectal cancer but availability and choice of drug will require a consultation with them and if the patient would join a phase I trial here, all treatment needs to occur here. Other major academic centers also have phase I programs that may be closer to home for this patient.

In conclusion, I concur with the management for this patient to date. There are no standard therapies I would offer at this time – the option would be consideration of a phase I trial.