Metastatic Colon Cancer After Failing 5-FU and CPT-11?
Metastatic Colon Cancer After Failing 5-FU and CPT-11?
A 77-year-old man with metastatic colon cancer failed therapy with 5-fluorouracil (5-FU) and was placed on CPT-11 325 mg/m every 3 weeks for 6 cycles. Follow-up computed tomography shows disease progression, with multiple new metastases in the lung and liver. His CEA decreased from 400 ng/mL to 300 ng/mL, and he is relatively asymptomatic clinically, with a performance status of < 2. What is the best step to take next in the treatment of this patient?
After randomized trials demonstrated that CPT-11 increased the survival of patients with colon cancer previously treated with 5-FU chemotherapy, CPT-11 became the treatment of choice for patients with previously treated colorectal cancer. Although subsequent studies demonstrated that the combination of 5-FU and CPT-11 increases survival compared with either agent alone, and although CPT-11 is now part of first-line treatment regimens, elderly patients or patients with poor performance status are still being managed with sequential rather than concomitant therapy, as is the case with the patient under discussion.
Unfortunately, once patients develop progressive disease after treatment with CPT-11, there is no effective therapy that can be recommended. The most effective approved agent in this situation is capecitabine, but the response rate and duration of response are very low. Oxaliplatin, which is also an active agent in this setting, is not approved in the United States.
The most appropriate recommendation for this patient would be enrollment in a well-designed clinical trial with new agents alone or in combination with effective standard agents, such as a combination of capecitabine or oxaliplatin with targeted compounds (eg, inhibitors of epidermal growth factor receptors [EGFR] or other signaling molecules). Another strategy investigated in this setting is the continuation of CPT-11, while adding agents that could potentially restore the susceptibility of the tumor to CPT-11. Indeed, the combination of C-225, a monoclonal antibody against the extracellular domain of the EGFR, resulted in a 22.5% response rate in this setting. However, concerns about the conduction of the trial and the lack of an arm addressing the activity of C-225 alone resulted in the refusal of the FDA to review the approval application for C-225 in this setting.
A 77-year-old man with metastatic colon cancer failed therapy with 5-fluorouracil (5-FU) and was placed on CPT-11 325 mg/m every 3 weeks for 6 cycles. Follow-up computed tomography shows disease progression, with multiple new metastases in the lung and liver. His CEA decreased from 400 ng/mL to 300 ng/mL, and he is relatively asymptomatic clinically, with a performance status of < 2. What is the best step to take next in the treatment of this patient?
After randomized trials demonstrated that CPT-11 increased the survival of patients with colon cancer previously treated with 5-FU chemotherapy, CPT-11 became the treatment of choice for patients with previously treated colorectal cancer. Although subsequent studies demonstrated that the combination of 5-FU and CPT-11 increases survival compared with either agent alone, and although CPT-11 is now part of first-line treatment regimens, elderly patients or patients with poor performance status are still being managed with sequential rather than concomitant therapy, as is the case with the patient under discussion.
Unfortunately, once patients develop progressive disease after treatment with CPT-11, there is no effective therapy that can be recommended. The most effective approved agent in this situation is capecitabine, but the response rate and duration of response are very low. Oxaliplatin, which is also an active agent in this setting, is not approved in the United States.
The most appropriate recommendation for this patient would be enrollment in a well-designed clinical trial with new agents alone or in combination with effective standard agents, such as a combination of capecitabine or oxaliplatin with targeted compounds (eg, inhibitors of epidermal growth factor receptors [EGFR] or other signaling molecules). Another strategy investigated in this setting is the continuation of CPT-11, while adding agents that could potentially restore the susceptibility of the tumor to CPT-11. Indeed, the combination of C-225, a monoclonal antibody against the extracellular domain of the EGFR, resulted in a 22.5% response rate in this setting. However, concerns about the conduction of the trial and the lack of an arm addressing the activity of C-225 alone resulted in the refusal of the FDA to review the approval application for C-225 in this setting.