Metastatic Uveal Melanoma Program
Treatment approach at Thomas Jefferson University for metastatic uveal melanoma
If surgery is possible ...
Surgical treatment for liver metastases:
Since the liver is the first and in many cases the only site of metastases in patients with uveal melanoma, local treatment aimed at controlling liver metastases holds promise in managing this otherwise highly chemoresistant tumor. We have reported that surgical removal of metastases can be useful in selected patients with excellent performance status and disease that is amenable to surgery (Aoyama et al, Cancer 2000.89; 7:1561-1568). However only 9% of patients with metastases were eligible for surgical intervention. If surgical removal of the metastases is feasible, patients would be referred to a hapten-modified melanoma vaccine study (Principle Investigator: Dr. David Berd).
If surgery is NOT possible ...
If patients do not have significant extra-hepatic (outside liver) metastases, liver metastasis will be treated by either immunoembolization or chemoembolization. Embolization of the hepatic artery has been used to treat primary liver cancer (hepatoma), as well as liver metastases from uveal melanoma, neuroendocrine tumors, colorectal cancer and leiomyosarcoma. The rationale for this approach is that liver tumors receive their blood supply mainly from the hepatic artery, while normal liver is supplied with blood from the portal vein.
If patients have significant extra-hepatic metastases, a systemic chemotherapy or an anti-angiogenesis treatment would be recommended.
Immunoembolization of liver metastases:
To improve the final outcome of uveal melanoma patients with liver metastases, we developed a new approach for liver metastases, IMMUNOEMBOLIZATION. In this approach, we will use drugs, so-called cytokines, instead of chemotherapy drugs, in the immunoembolization treatment of the patients. Cytokines have been reported to stimulate or modulate immune responses. The cytokines that have been used for immunoembolization at Thomas Jefferson University Hospital include GM-CSF, interleukin 2 (IL-2) and interferon alpha (IFN-alpha).
The rational of the immunoembolization is as follows:
• Embolization of the hepatic artery provides a major ischemic attack on liver tumors and provide tumor antigens to immune system.
• Local infusion of an immunostimulant may induce an inflammatory response in the tumor, which eliminates residual tumor cells.
• Local stimulation of immune system may result in development of a systemic immune response against tumor cells, which suppresses the growth of extra-hepatic metastases.
Chemoembolization of liver metastases from uveal melanoma:
Chemoembolization of hepatic metastasis from uveal melanoma was first reported by the group from the MD Anderson Cancer Center (Mavligit et al. JAMA 260:974-6, 1988). Cisplatin was used as chemotherapy medication. They reported that 14 out of 30 patients showed regression of liver metastases. The duration of response was 2-6 months (median 6 months). Median survival of responder was longer than 14 months.
Unfortunately, our follow up study at Thomas Jefferson University failed to reproduce their excellent results (Sato et al., Proc ASCO 14; 415, 1995). No patient has regression of liver metastases and median survival of patients was 7.1 months.
We subsequently developed a new chemoembolization treatment at Thomas Jefferson University Hopsital, replacing Cisplatin with a different type of chemotherapy medication, BCNU. In our phase II clinical study, we were able to demonstrate better results (Patel et al., Proc ASCO 20: 356a, 2001). The summary of our study is as follows:
Response (n=28):
| 1 |
complete regression (CR) |
| 4 |
partial responses (PR; more than 50% shrinkage of tumor) |
| 16 |
stable disease (SD) |
| 7 |
progressive disease (PD) |
Overall survival: median 5.8 months (1 to 27.6 months)
| The overall survival was dependent on the following factors: |
| (1) Response to the treatment |
| CR+PR |
15.5 months (5.4 to 27.6 months) |
| SD |
7.4 months (2.9 to 27.3 months) |
| PD |
2.1 months (1.0 to 5.7 months) |
| (2) Volume of the liver metastases (how much liver volume was replaced by the metastases) |
| <20% liver involvement |
14.4 months |
| 20-50% liver involvement |
5.6 months |
| >50% liver involvement |
4.9 months |
In this clinical trial, two thirds of patients subsequently developed progression in extra-hepatic sites.
