A matrix metalloproteinase inhibitor to treat unresectable cholangiocarcinoma
J J French1, M J Midwinter, M K Bennett
1Hepato-Pancreato-Biliary Surgical Unit, Royal Hospital Haslar, Portsmouth, UK.
Abstract:
Matrix metalloproteinases (MMPs) are implicated in tumour invasion and metastasis. We report the first use of an MMP inhibitor to treat unresectable cholangiocarcinoma. Four men with stage IV cholangiocarcinoma received oral Marimastat (10 mg bd) indefinitely following relief of obstructive jaundice. Monthly measurements of the tumour marker CA 19-9 were used as an indicator of disease response and activity. CA 19-9 levels dropped sharply and stayed low in the two patients who appeared to respond. Mean survival of the four patients was 21.5 months (range 4-48 months). Side effects were well tolerated. A more extensive and detailed examination of MMP inhibitors to treat cholangiocarcinoma is indicated.
Insights
This study explored matrix metalloproteinase (MMP) inhibitors for advanced cholangiocarcinoma. Two of four patients showed promising results with Marimastat, indicating potential for MMP inhibitors in treating this cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Matrix metalloproteinases (MMPs) play a role in cancer progression, including tumor invasion and metastasis.
- Cholangiocarcinoma is a challenging cancer with limited treatment options for advanced stages.
Purpose of the Study:
- To investigate the efficacy of an MMP inhibitor, Marimastat, as a treatment for unresectable cholangiocarcinoma.
- To assess tumor marker CA 19-9 levels and patient survival as indicators of treatment response.
Main Methods:
- Four male patients with stage IV cholangiocarcinoma received oral Marimastat (10 mg twice daily) after relief of obstructive jaundice.
- Tumor marker CA 19-9 levels were monitored monthly to assess disease response.
- Patient survival was tracked for the duration of the study.
Main Results:
- Two of the four patients exhibited a sharp decrease and sustained low levels of CA 19-9, suggesting a positive response to Marimastat.
- The mean survival for the four patients was 21.5 months, with a range of 4 to 48 months.
- Reported side effects were generally well tolerated by the patients.
Conclusions:
- Matrix metalloproteinase (MMP) inhibitors, such as Marimastat, show potential as a therapeutic strategy for unresectable cholangiocarcinoma.
- Further extensive clinical trials are warranted to validate these preliminary findings and explore the role of MMP inhibitors in cholangiocarcinoma treatment.