Treatment of Recurrent Esophageal Cancer
Medically reviewed by C.H. Weaver M.D. 08/2018
Patients with recurrent esophageal cancer have cancer that has recurred after primary treatment.
There are currently no standard curative therapies for treatment of recurrent esophageal cancer. The predominant symptom of esophageal cancer is dysphagia, which simply refers to 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 a patient’s survival. A number of treatment options are currently utilized alone or in combination to achieve optimal results.
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.
Patients who have recurrent cancer after chemotherapy and/or radiation therapy can be treated with esophagectomy. However, there are usually more surgical complications in patients who have received prior radiation therapy than in patients who undergo surgery as primary treatment.
Patients who fail surgery alone can often be treated successfully with radiation therapy with or without chemotherapy. Radiation therapy can be extremely effective in temporarily controlling local symptoms from esophageal cancer.
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 and precision cancer medicines are incorporated into regimens, this may continue to improve.
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.
Studies have indicated 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®.
At ASCO 2019 doctors reported that FOLFIRI (fluorouracil, leucovorin and irinotecan) plus Cyramza (ramucirumab) was associated with fewer serious side effects and had an improvement in overall objective response and disease control compared with Cyramza plus paclitaxel. (1)
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.
Chemotherapy and Radiation Therapy
For patients who have not received radiation or chemotherapy, these treatments can be combined. One study evaluated 19 patients with recurrence of esophageal squamous cell cancer after surgical treatment. Thirteen patients had recurrences in the local area and 6 had metastatic cancer. Treatment of recurrence was combined chemotherapy and radiation therapy for 12 patients. Other treatments included chemotherapy alone, esophageal prosthesis or surgery. There were 7 objective responses among the group treated with chemotherapy and radiation therapy and none in the patients treated with chemotherapy alone. Survival of the 12 patients treated by combined radiation and chemotherapy was 66% at one year and 22% at 2 years with an average survival time of 16 months. These doctors concluded that active medical treatment of recurrent esophageal cancer by combined chemotherapy and radiation therapy provided a significant prolongation of survival with moderate toxicity.
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. In a large study of 154 patients in whom a total of 3,140 dilators were passed before, during and after radiation therapy there were two perforations. The duration of symptom relief after successful dilatation varies from days to weeks.
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.
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 recurrent 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.
- Lorenzen S, et al. Abstract 4023. Presented at: ASCO Annual Meeting; May 31- June 4, 2019; Chicago.