Hello,
Thanks for requesting me to answer your question.
You asked a question regarding options other than chemotherapy in
treating stage IV colon cancer. Here are some of the alternatives to
systemic chemotherapy to stage IV colon cancer. Isolated hepatic
metastases from colorectal cancer (CRC) are a significant clinical
problem. The liver is the dominant metastatic site in patients with
metastatic CRC, and the majority of such patients will die of liver
failure. Although two-thirds of these patients have extrahepatic
disease, some have disease that is truly isolated to the liver. For
patients with isolated liver metastases, regional treatment approaches
may be considered as an alternative to systemic chemotherapy.
1) Surgical resection
The only curative option for patients with liver-isolated CRC is
surgical resection. In patients with four or fewer isolated hepatic
lesions, resection may be curative, with five year relapse-free
survival rates ranging from 24 to 38 percent (2). However, no more
than ten percent of patients with isolated hepatic metastases are
amenable to potentially curative resection. The majority are not
candidates for resection because of tumor size, location,
multifocality, or inadequate hepatic reserve. Nevertheless, because of
its impact on survival, surgical resection is the treatment of choice
when feasible.
2) Tumor ablation
In patients who are not candidates for potentially curative resection,
palliative regional approaches include local instillation of ethanol
or acetic acid directly into the tumor, cryosurgery, and hyperthermic
or microwave coagulation. In general, lesions that are amenable to
surgical resection also lend themselves to ablative treatments. Thus,
these methods may be considered a less morbid alternative to surgical
resection in patients who are at high risk for surgery or for whom the
impact of surgical treatment on survival is negligible.
a) Percutaneous ethanol or acetic acid injection
Percutaneous injection techniques have been most widely applied to
small hepatocellular cancers. In such patients, intratumoral injection
of acetic acid appears to more effective than injection of ethanol
(alcohol). Histologies other than hepatocellular cancer have not
responded as well to percutaneous injection of ethanol or acetic acid,
perhaps because of difficulties in achieving equal distribution
throughout the metastatic lesion. Percutaneous acetic acid injection
has not been adequately studied for such lesions.
b) Cryotherapy
Cryotherapy and hyperthermic coagulative necrosis via microwaves or
radiofrequency waves are two additional methods for local ablation of
small metastatic liver tumors. Like percutaneous alcohol injection,
these therapies are limited by the difficulty in determining the true
margin of the lesion, which often extends beyond the leading edge, and
the lack of specificity of tissue damage. Cryotherapy is ideally
suited for lesions that are less than 5 cm since the zone of necrosis
that is formed is 3 to 5 cm in size. This procedure currently requires
laparotomy, although laparoscopic procedures are beginning to be
performed.
In one review of the available literature comparing cryosurgery to
surgical resection in patients with hepatic colorectal metastases, the
overall and disease-free survivals for patients treated by cryosurgery
were were 33 to 64 percent, and 22 to 29 percent, respectively (3).
c) Hyperthermic coagulation
Hyperthermic coagulative necrosis can be accomplished by microwaves or
radiofrequency waves. In contrast to cryosurgery which requires
operative intervention, this procedure can be performed
percutaneously.
3) Radiofrequency ablation
Radiofrequency ablation (RFA) using cooled-tip electrodes produces
larger volumes of coagulation necrosis with fewer electrode insertions
than with other RFA techniques.
Long-term outcome following RFA was studied in 117 patients with 179
metachronous metastases from CRC, in whom follow-up CTs were performed
every 4 months. Local recurrence developed in 39 percent, and was
related to lesion size; 66 percent developed new liver metastases. The
estimated one-, two-, and three-year survival rates were 93, 69, and
46 percent respectively, and were unrelated to the number of treated
metastases (4).
4) Microwave coagulation
Microwave coagulation can cut liver, and prevent bleeding from this
cut edge by coagulating the cut end simultaneously. Although best
studied for treatment of small hepatocellular cancers, microwave
coagulation is beginning to be used for metastatic liver tumors.
5) Gene therapy
Non-conventional anti-cancer agents, such as viruses, liposomes and a
variety of gene therapy vectors, may also be better administered via
the hepatic artery. The preferential vascular supply of tumors in the
liver from the hepatic artery may enable a relative "targeting" of the
agent. A few clinical studies are underway evaluating such biologics.
6) Monoclonal therapes
The success of targeted monoclonal therapies against several
malignancies (eg, trastuzumab for breast cancer and rituximab for
B-cell non-Hodgkin's lymphomas) in combination with an increased
understanding of biologic processes important for survival and
proliferation of colorectal cancer cells provides impetus for
evaluating the potential therapeutic utility of targeted therapy for
CRC. New agents are being developed utilizing knowledge about the
biochemical and molecular features of specific targets. Some of the
known biological processes that might be important in survival or
proliferation of colorectal cancer cells include:
- p53, which plays a critical role in controlling a number of cellular
processes, including DNA integrity, progression through the cell
cycle, and apoptosis, and is mutated in approximately 50 percent of
colorectal adenocarcinomas.
- Ras mutations, which occur in approximately 30 to 50 percent of
colorectal adenocarcinomas, and correlate with tumor aggressiveness
- Growth factors may be involved in the proliferation of colorectal
cancer cells or the development of angiogenesis or metastases. A
monoclonal antibody directed against the specific growth factor - EGF
receptor, IMC-225 (cetuximab, Erbitux®), has entered clinical trials.
- Intracellular signaling pathways, such as the COX-2 pathway that is
important in proliferation of colonic polyps and may play a role in
malignant cells as well
- Tumors that have inactivating mutations of DNA repair genes have a
characteristic genetic signature which is found in approximately 15
percent of sporadic colorectal cancers. These cancer cells are
resistant to many cytotoxic drugs, including 5-fluorouracil. A case
report suggests that they may be sensitive to calcium channel
blockers, such as nifedipine.
7) Immunotherapeutic approaches
Several immunotherapy approaches have been explored in the adjuvant
setting of resected colon cancer. Among them are administration of the
monoclonal antibody 17-1A and active specific immunotherapy.
Edrecolomab (Panorex®)
The mouse/human chimeric monoclonal antibody 17-1A (edrecolomab)
recognizes a 41-kD human colon carcinoma-associated antigen.
In a German study, 189 patients with resected Dukes' C colorectal
cancer were randomly assigned to observation or a four month regimen
of Edrecolomab (100 mg IV monthly) (1). At a median follow-up of five
years, antibody treatment reduced the risk of death by 30 percent and
the risk of recurrence by 27 percent. Treatment-related toxic effects
were infrequent. The magnitude of this benefit is approximately the
same as has been reported with systemic 5-FU-based chemotherapy for
stage III disease.
8) Hepatic intraarterial chemotherapy
Surgeon-ga has mentioned about hepatic intraarterial chemotherapy. As
I have mentioned before, in patients with metastatic CRC that is
limited to the liver, surgical resection provides a long-term,
relapse-free survival in approximately 25 percent. The liver is the
dominant site of recurrence in one-half of patients undergoing
potentially curative hepatic resection. Given the proven efficacy of
adjuvant 5-FU-based chemotherapy in node-positive patients, it is a
logical step to evaluate hepatic arterial infusion (HAI) therapy
following metastatectomy of hepatic lesions. HAI has predominantly
been evaluated in patients with unresectable metastatic disease that
is limited to the liver. However, there has not been a consistent
survival advantage in these small studies.
I hope that this provides some information when you next talk to your
oncologist. As Surgeon-ga has mentioned, there is no definitive
curative treatment for stage IV colorectal cancer.
I stress that this answer is not intended as and does not substitute
for medical advice - please see your primary care physician for
further evaluation of your individual case.
Please use the answer clarification to ask any questions before rating
this answer. I will be happy to explain any issue.
Thanks,
Kevin, M.D.
Search strategy:
No internet search engine was used in this answer. All sources are
from objective, physician-written, peer-reviewed resources.
Bibliography:
1) Riethmuller, G, Schneider-Gadicke, E, Schlimok, G, et al.
Randomised trial of monoclonal antibody for adjuvant therapy of
resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study
Group. Lancet 1994; 343:1177.
2) Scheele, J, Stang, R, Altendorf-Hofmann, A, Paul, M. Resection of
colorectal liver metastases. World J Surg 1995; 19:59.
3) Tandan, VR, Harmantas, A, Gallinger, S. Long-term survival after
hepatic cryosurgery versus surgical resection for metastatic
colorectal carcinoma: a critical review of the literature. Can J Surg
1997; 40:175.
4) Solbiati, L, Livraghi, T, Goldberg, SN, et al. Percutaneous
radio-frequency ablation of hepatic metastases from colorectal cancer:
long-term results in 117 patients. Radiology 2001; 221:159.
5) Venook. Regional treatment strategies for metestatic colorectal
cancer. UptoDate, 2002. |
