Stage IV Esophageal Cancer

Overview

Patients with stage IV esophageal cancer have metastatic cancer that has spread to distant sites.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage IV esophageal cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Optimal treatment of patients with stage IV esophageal cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons, gastroenterologists and nutritionists.

There are currently no standard curative therapies for treatment of stage IV esophageal cancer. The predominant symptom of esophageal cancer is dysphagia, which simply means difficulty in swallowing food and liquids. There are specific treatments that can be administered that can result in short-term benefit and improvement in nutrition. Current treatment approaches are primarily directed at controlling the symptoms of cancer and prolonging survival. A number of treatment options are currently utilized alone or in combination to achieve optimal results.

Surgery for Palliation

Patients with stage IV esophageal cancer often have widespread cancer at the time of diagnosis and cannot be cured with surgery. There is controversy over how best to treat patients who cannot undergo surgery with curative intent. In one clinical study, doctors compared the outcomes of 39 patients with stage IV esophageal cancer who underwent an esophagectomy for palliation with the outcomes of 49 patients with stage IV esophageal cancer who underwent more complete removal of cancer. Both groups of patients experienced significant improvement with regard to both the quantity and quality of food intake and a reduction in the severity of eating related symptoms. After 9 months, patients in the palliative group experienced more pain and a poorer quality of life, but there were no differences in sleep, leisure activity and performance scores when compared to the other group. This study suggests that palliative esophagectomy relieves symptoms in the majority of patients with inoperable esophageal cancer. It could also be argued that both groups had palliative surgery since the majority of patients who undergo surgery with curative intent have rapid recurrence of cancer in the first year or two after surgery. To learn more, go to Surgery and Cancer of the Esophagus.

Chemotherapy

Single chemotherapy drugs such as Platinol®, fluorouracil, Mutamycin®, doxorubicin, and Ellence® can result in clinical remissions in patients with esophageal cancer. Historically, standard chemotherapy treatment regimens often utilized Platinol®, flourouracil and Ellence® or Mutamycin®. The overall response rate for these combination regimens is approximately 40% and the average survival duration is 8-10 months. Recent studies indicate that taxanes (paclitaxel and Taxotere®) may be the most active single chemotherapy drugs for the treatment of esophageal cancer, with complete remissions occurring in up to 15% of patients. Other agents that have been or are being evaluated include Camptosar® and Gemzar®. All current clinical trials involve various combinations of drugs.

For example, in a recently published clinical trial, 61 patients with advanced unresectable or metastatic esophageal cancer were treated with Platinol®, fluorouracil and paclitaxel. Thirty patients had adenocarcinoma and 31 had squamous cell cancer. The overall response rate was 48% for all patients; however, the complete response rate was 20% for patients with squamous cancer and only 3% for patients with adenocarcinoma. The average duration of response was 5.7 months and the average survival was 10.8 months. There were no treatment related deaths. This regimen resulted in a complete response rate of 20% in patients with squamous cell cancer, which is higher than other reported regimens.

Camptosar® is another new chemotherapy drug with activity against cancers of the gastrointestinal tract. In one study, 35 patients with metastatic or unresectable adenocarcinoma or squamous cell esophageal cancer were treated with a combination of Camptosar® and Platinol®. Major clinical responses were observed in 20 patients (57%) and 2 patients experienced complete disappearance of their cancer. Responses were observed both in patients with adenocarcinoma and those with squamous cell carcinoma. The average duration of response was 4 months. In 20 patients with difficulty swallowing, 90% had improvement or resolution of their symptoms. Responding patients also experienced an improvement in their quality of life, primarily because of reductions in pain and improvement in their emotional state. The therapy was well tolerated and side effects were relatively mild.

Currently available combination chemotherapy treatment for stage IV cancer results in complete remission in up to 20% of patients, with average survival of 8-12 months. As newer drugs, such as the taxanes, Camptosar®, and Gemzar®, are incorporated into regimens, this may continue to improve.

Other Treatment Modalities

Many other treatment modalities are utilized to prolong survival and quality of life for patients with esophageal cancer.

Thermal laser: Thermal laser coagulation performed by endoscopy can provide temporary relief of dysphagia. Laser ablation appears to be most helpful for treating polypoid cancers that grow into the esophagus causing occlusion. Laser treatment is less effective for upper esophageal cancers or cancers of the gastroesophageal junction. A multi-center clinical trial has compared photodynamic laser therapy to thermal laser ablation for the palliation of patients with esophageal cancer who experience difficulty swallowing food. In general, photodynamic laser therapy was more effective than thermal laser treatment.

Photodynamic treatment: Photodynamic ablation has been used for the palliation of patients with esophageal cancer. Photodynamic treatment involves injection of a light sensitizer into a vein, which is then taken up by cells. A laser is then directed at the cancer cells. The reaction between the laser and the light sensitizer destroys the cells. The objective response rate at one month with this approach has been reported to be 32% for patients receiving photodynamic laser treatment, which compared favorably to the 20% reported for patients receiving thermal-laser treatment.

Esophageal dilatation: Frequently, after the administration of chemotherapy, radiation therapy, laser or photodynamic treatment, the area of the esophagus with cancer can be constricted or narrowed. Narrowing of the esophagus may be due to recurrent cancer or to treatment induced strictures or both. Relief of this constriction by dilation can temporarily improve swallowing. During esophageal dilation, a physician uses endoscopic or fluoroscopic guidance to pass flexible dilators (mercury filled rubber tubes) through the mouth. Increasing diameters of dilators, called bougies, are gradually introduced until the difficulty in swallowing resolves. One clinical study reported a 92% success rate for dilation. The duration of symptom relief after successful dilatation varies from days to weeks. One complication of esophageal dilation is the potential for perforation; however, this occurs only rarely. In a large study of 154 patients, a total of 3,140 dilators were passed before, during and after radiation therapy and resulted in only two perforations.

Esophageal stents or prostheses: Stents are rigid tubes that stay in the esophagus to keep it open. Recently, a clinical study evaluated the use of esophageal stents over a 4-year period for the management of patients with inoperable esophageal cancer. In a group of 160 patients with esophageal cancer,159 had stents placed successfully. In this study, a traditional rigid tube was placed in 84 patients and metallic self-expanding stents were placed in 75 patients. After placement of the stents, chemotherapy and/or radiation therapy was administered to 82 patients. The results indicated that 11% of patients had complications, including displacement of the stent, incomplete expansion of the stent, perforation of the esophagus or bleeding. Swallowing was improved in 97% of patients. These doctors concluded that placement of stents to improve swallowing was a relatively safe palliative procedure. Self-expanding metallic stents were thought to be preferable to rigid stents for maintaining an open esophagus.

Strategies to Improve Treatment

The progress that has been made in the treatment of esophageal cancer has resulted from improved patient and physician participation in clinical studies. Future progress in the treatment of esophageal cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of esophageal cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Supportive Care.

New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research carried out in phase II clinical trials. These studies are performed in patients with stage IV or recurrent esophageal cancer.

Phase I Trials: New chemotherapy drugs or other anti-cancer therapies continue to be developed and evaluated in phase I clinical trials. The purpose of phase I trials is to evaluate new therapies in order to determine the best way of administering the drug and to determine whether the drug has any anti-cancer activity in patients with esophageal cancer. Patients with stage IV esophageal cancer should consider participation in phase I trials.

Multiple Drug Resistance Inhibitors: Esophageal cancer can be drug resistant at the outset of treatment or develop drug resistance after treatment. Several drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in esophageal and other cancers.

Gene Therapy: Currently, there are no gene therapies approved for the treatment of esophageal cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunction gene or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer death or efforts to make the immune system kill cancer cells. A few gene therapy studies are being carried out in patients with esophageal cancer.

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