Metastatic liver cancer

Konno, T. Kai, Y. Yamashita, R. Nagamitsu, A. Kimura, M. Targeted chemotherapy for unresectable primary and metastatic liver cancer. Acta Oncology 1994, 33, 133-137. 

Brown 1987b). Additionally, one of the two liver cancers was not a primary carcinoma as it metastasized from another site (unknown). If the metastatic liver cancer is not included in the analysis, the SMR for liver and biliary tract cancer in the whole cohort loses statistical significance (SMR=210, p 0.05) (Nicholson and Landrigan 1994). Other findings included a slight increase in rectal cancer in the first study, but not in the follow-up (see Section 3.2.8.2.3). Limitations of these studies include small number of deaths, relatively short periods of observation, and possible misclassification of the cause of death because it is not clear in every case if death was due to primary cancer of the liver, biliary tract, or gall bladder. 

Terayama N, Terada T, Nakantrma Y. An immrmohistochemi-cal study of trrmour vessels in metastatic liver cancers and the surrounding liver tissue. Histopathology. 1996 29 37-43. 

Falconi M, Bassi C, Bonora A, Sartori N, Procacci C, Talamini G, Mansueto GC, Pederzoli P (1999) Role of chemoembolization in synchronous liver metastases from pancreatic endocrine tumours. Dig Surg 16 32-38 Feun LG, Reddy KR, Yrizarry JM et al (1994) A phase 1 study of chemoembolization with cisplatin and lipiodol for primary and metastatic liver cancer. Am J Clin Oncol 17 405-410... 

In practice, despite its promising concept of design, TACE has not shown yet to be as effective and potent as in theory. Several challenging obstacles that have not been exceeded yet include chemotherapeutic dose-limiting toxicity, development of mechanisms for drug resistance and tumor revascularization. Moreover, the techniques and agents used for intra-arterial treatment of primary and metastatic liver cancer are very heterogeneous. This hinders a more systematic approach and interpretation of the results of clinical trials as well as implementation of meta-analyses. 

The ideal chemotherapeutic agent for transcatheter treatment of primary and metastatic liver cancer is yet to be developed. This agent should combine effectiveness against the tumor and reduced toxicity to the normal or cirrhotic liver. In the near future, some of the above novel drugs are expected to enter the clinical arena and be prospectively tested, whereas some of the currently used chemotherapeutic agents such as doxorubicin, cisplatin and mitomycin C are expected to be tested in a more systematic and prospective way. 

Metastatic breast cancer is not curable, and therapy is intended to palliate symptoms. In most cases, hormonal therapy is the mainstay. While on therapy, patients are monitored monthly for signs of disease progression or metastasis to common sites, such as the bones, brain, or liver. 

First generation of topi inhibitors were developed as drugs from camptothecins, a family of compounds derived from wood and bark of the Chinese tree Camptotheca acuminata) [9, 10], Many of these are already in clinical use or clinical trials, including irinotecan, topotecan, exatecan, rubitecan, and lurtotecan. Irinotecan (CPT-11) is bioactivated in liver by carboxylesterase to the active metabolite SN-38, 1000-fold more active [11]. Irinotecan received in 1998 FDA approval for treatment of metastatic colorectal cancer after failure of treatment with 5FU [12],... 

Irinotecan is a prodrug that is converted mainly in the liver by the carboxylesterase enzyme to the SN-38 metabolite, which is 1000-fold more potent as an inhibitor of topoisomerase I than the parent compound. In contrast to topotecan, irinotecan and SN-38 are mainly eliminated in bile and feces, and dose reduction is required in the setting of liver dysfunction. Irinotecan was originally approved as second-line monotherapy in patients with metastatic colorectal cancer who had failed fluorouracil-based therapy. It is now approved as first-line therapy when used in combination with 5-FU and leucovorin. Myelosuppression and diarrhea are the two most common adverse events. There are two forms of diarrhea an early form that occurs within 24 hours after administration and is thought to be a cholinergic event effectively treated with atropine, and a late form that usually occurs 2-10 days after treatment. The late diarrhea can be severe, leading to significant electrolyte imbalance and dehydration in some cases. 

Megestrol acetate has also proved of value in patients with metastatic prostatic cancer, epithelial ovarian cancer, or malignant melanoma and is therefore used in both sexes. The adverse effects are very similar in men to those seen with oncological doses in women loss of libido and potency is likely to occur in male patients. In one clinical study of 43 men with recurrent and metastatic cancer of the prostate given megestrol acetate 160 mg/ day orally, five developed a symptomatic rise in liver... 

Primary liver cancer, or HCC, is a rare type of cancer in Western countries, but occurs frequently in Africa and Asia. HCC is often the sequel to chronic viral hepatitis, cirrhosis, nutritional deficiencies, or specitic toxins. More common types of cancer occurring in the liver are metastatic diseases, which originate mainly from primary gastrointestinal tumors. For the growth of these and other solid tumors, sprouting of the vascular system, called angiogenesis, is essential to provide an adequate blood supply to the tumor cells. Nutrients and oxygen are needed for the proliferation of tumor cells [134-136],... 

Systemic chemotherapy is usually not indicated in non-colorectal liver metastases due to lack of response. The systemic administration of cytostatics (also in combination) possesses the status of palliative therapy. However, in metastatic neuroendocrine tumours, a combination of octreotide -i- IFN had a positive effect on the survival time. Systemic chemotherapy produced remission rates of up to 60%. (320) In metastatic breast cancer, systemic chemotherapy is indicated, usually in combination with hormonal and immune therapy. (316, 342) In metastatic gastric carcinoma, palliative chemotherapy can achieve a remission rate of up to 40%, with a slight extension of survival time. 

Okano, K., Yamamoto, X, Kosuge, T., Yamamoto, S., Sakamoto, M., Nakanishi, Y., Hirohashi, S. Fibrous pseudocapsule of metastatic liver tumors from colorectal carcinoma - clinicopathologic study of 152 first resection cases. Cancer 2000 89 267-275... 

Fatal cholestatic hver failure occurred in a 45-year-old woman with metastatic breast cancer who was given gemcitabine and carboplatin and pre-existing liver damage. After four courses of gemcitabine -I- carboplatin she developed severe decompensated cholestatic hepatitis (9). Liver biopsy showed marked cholestasis and hepatocellular injury consistent with drug-induced hepatotoxicity. 

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