Regional Therapy
for Metastatic Cancer Improves Outcomes
January / February 2003
Surgical oncologists at the Abramson Cancer Center of the
University of Pennsylvania offer patients new regional therapy
treatment options for metastatic disease that is confined
to one area of the body, particularly the liver, the peritoneal
cavity and the extremities. Radio frequency ablation, intra-arterial
infusion pumps, photodynamic therapy, and isolated limb perfusion
provide patients with the hope of improved tumor responses,
longer survival rates, and a better quality of life.
Radio Frequency Ablation for Liver Cancer
Penn surgical oncologists utilize radio frequency ablation
for primary hepatomas or metastatic tumors to the liver
when it is impossible to resect these tumors. An electrode
is placed precisely in the center of the tumor and an
electrical current destroys malignant cells by applying
heat within a four to five centimeter diameter.
For patients
with colon cancer that has metastasized to the liver,
this treatment can completely destroy tumors that are
otherwise unresectable. "With rare
exceptions, systemic chemotherapy alone has fairly limited
curative results or durable response in most solid tumors,"
says Douglas
L. Fraker, MD, chief of surgical oncology at the Abramson
Cancer Center.
Surgical resection is the preferred treatment for metastatic
colon cancer when the disease is isolated to one area of the
liver. However, radio frequency ablation (RFA) used in combination
with surgical excision or RFA alone for nodules that are unable
to be resected has shown to be an effective treatment. The
local recurrence rate when nodules are smaller than the thermal
lesion (less than four centimeters) has been one to two percent.
The only side effect is local infection in the treated nodule,
which was seen in just one percent of cases.
Intra-arterial Infusion Pump for Liver Cancer
Although the intra-arterial infusion pump has been around
for many years, it is not widely accepted among medical oncologists
because of problems with liver toxicity. Placed under the
skin, the pump delivers continuous chemotherapy to the liver
via the hepatic artery. The pump has a 50 to 75 percent response
rate compared to systemic chemotherapy, which offers a 20
to 35 percent response rate. Randomized trials completed in
the 1980s did not show an improvement in survival with intra-arterial
therapy, but current pump regimens with better responses and
less toxicity are in use today.
Recent randomization studies from Memorial Sloan-Kettering
and the Southwest Oncology Group (SWOG), showed significant
improvement of survival rates when the pump was used as an
adjuvant treatment after liver resection of colorectal metastases
compared with resection alone. By placing the pump after liver
resection, local recurrence rates decrease due to the chemotherapy
attacking any microscopic residual disease. Radio frequency
ablation can be added to this treatment modality to further
debulk disease prior to intra-arterial chemotherapy.
"As part of a Phase II clinical trial, we not only use the
pump as an adjuvant treatment after resection, we also place
pumps in patients who undergo resection and radio frequency
ablation in patients with extensive colorectal metastases.
These patients are very likely to have nodules recur in their
remaining liver. By adding the intra-arterial pump, we have
decreased the local recurrence rate and improved overall survival,"
explains Dr. Fraker. The estimated median survival in 40 patients
who had this multimodality approach was 23 months. Systemic
chemotherapy has a median survival of 10 to 12 months in a
similar patient population.
The intra-arterial pump has few side effects, the most common
and the most important being chemical hepatitis. Liver function
studies need to be closely monitored and chemotherapy doses
and treatments require adjustments according to lab findings
or patients may develop sclerosing cholangitis.
Photodynamic Therapy for the Peritoneal Cavity
In addition to liver metastasis, many cancers spread to various
surfaces of the peritoneal cavity, a condition called carcinomatosis.
Due to the large number and widespread distribution of
nodules,
chemotherapy, radiation, or surgery alone cannot treat the
spread of this disease. Penn currently has the only protocol
in the world for a new experimental treatment modality
utilizing
photodynamic therapy in the peritoneal cavity. The therapy
involves administering a sensitizer drug that is retained
in the tumor cells and clears from the normal cells within
48 hours. The surgeon removes all nodules larger than five
millimeters and exposes all peritoneal surfaces. A radiation
oncologist then administers laser treatment with a specific
wavelength to activate the sensitizer and destroy the malignant
cells.
"Research is ongoing for new sensitizers and new methods
for distributing the energy more evenly. Evidence shows that
a patient's disease can remain stable for months or even years,
but unfortunately patients with this type of cancer usually
succumb to recurrence," adds Dr. Fraker.
Isolated Limb Perfusion for Metastatic Melanoma
Penn surgical oncologists are participating in clinical trials
using isolated limb perfusion for the treatment of metastic
melanoma. The procedure entails recirculating chemotherapeutic
agents combined with heat through the leg. "Because the
drug is not metabolized nor does it affect the bone marrow,
larger
doses of chemotherapy can be used, therefore, improving response
rates," says Dr. Fraker, who recommends this treatment
for the approximate five to 10 percent of extremity
melanoma patients
who have intransit nodules of the skin throughout the extremity.
When using the drug melphalan, there is a 55 percent complete
response compared to only a five percent response to systemic
chemotherapy. An ongoing national trial is recruiting patients
with intransit melanoma confined to the extremity and randomizes
patients to receive melphalan or melphalan plus a protein
called tumor necrosis factor.
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