The combination of cisplatin and irinotecan has significant anti-tumor activity in esophageal cancer. Oxaliplatin has been shown to have activity in combination with 5-Fluorouracil (5FU) and radiation in treatment of locally advanced esophageal cancer. Oxaliplatin also has better side effects profile than cisplatin and may be able to overcome tumors that have developed cisplatin resistance. The standard treatment of locally advanced esophageal cancer has been cisplatin, 5FU and radiation followed by possible esophagectomy. However, a large portion of these patients will relapse and the tumor may develop resistance to cisplatin and/or the cumulative toxicity from previous treatment forbids the use of cisplatin again. Weekly combination of oxaliplatin and irinotecan has been shown to be active and well tolerated in elderly population with refractory colorectal cancer. Therefore, we propose this phase II trial of a weekly oxaliplatin and irinotecan to test the effectiveness and the tolerability of this regimen in metastatic and/or recurrent esophageal cancer.
Esophageal cancer represents the seventh cause of cancer death in American men, and more than 90% of patients diagnosed with esophageal cancer will ultimately die of their disease. In the United States, 13,900 new cases of esophageal cancer and 13,000 deaths from esophageal cancer are anticipated in 2003 (Jemal et al, 2003). The lifetime risk of esophageal cancer is 0.8% for men and 0.3% for women (Ries et al, 2002). The risk increases with age, with a mean age at diagnosis of 67 years (Ries et al, 2002; Daly et al, 2000). Adenocarcinoma of the esophagus or gastroesophageal junction, a previously rare disease, is rapidly increasing in incidence in the United States and western countries and now accounts for more than half of newly diagnosed disease (Devesa et al, 1998). Half of patients diagnosed with esophageal cancer present with overt metastatic disease, and chemotherapy is the mainstay of palliation in this setting. In patients who present initially with locoregional disease, the majority will eventually develop metastatic disease as well, with or without local recurrence of disease. Metastatic esophageal carcinoma is an incurable disease with median survival duration of 4 to 8 months. Combination chemotherapy, most often cisplatin-based, results in partial responses in 25% to 50% of patients with metastatic disease and rare complete responses, including a 35% response rate reported for the commonly used combination of cisplatin and fluorouracil (Ilson et al, 1996). Recent chemotherapy trials indicate an overlap in response rates for metastatic adenocarcinoma and squamous carcinoma carcinoma of the esophagus (Ilson et al, 1997). Responses to chemotherapy are generally short-lived, and toxicity of cisplatin-based chemotherapy, particularly in the palliation of metastatic disease, is often substantial and underscores the need to identify new agents in the treatment of esophageal carcinoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
40 mg/m2 IV over 60 minutes Every 21 days
60 mg/m2 IV over 60 minutes, immediately following oxaliplatin Every 21 days
Chao Family Comprehensive Cancer Center
Orange, California, United States
To assess the overall response rate
To assess the overall response rate (complete and partial response) to a weekly combination of oxaliplatin and irinotecan in patients with unresectable or metastatic esophageal cancer or cancer of the gastro-esophageal (GE) junction.
Time frame: 5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v3.0
To assess the frequency and severity of toxicities associated with this treatment
Time frame: 5 years
Progression Free Survival
from date of registration to date of first observation of progressive disease (as outlined in 10.2d), death due to any cause or symptomatic deterioration.
Time frame: 5 years
Evaluation of Time to Death
Analysis timeline would be from the date of registration to date of death due to any cause.
Time frame: 5 years
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