Mitomycin C-loaded microcapsules in the treatment of colorectal liver metastases: pharmacokinetics of regionally administered particulate chemotherapy

Article Abstract:

The ideal cancer drug would distinguish between normal and cancerous cells, sparing all the former and killing all the latter. Unfortunately, this drug has not been found, and all chemotherapeutic treatments represent a compromise between the desirable killing of cancer cells and the undesirable destruction of healthy tissues. Different techniques of administering conventional chemotherapeutic agents have been tried to improve the destruction of cancerous cells without increasing the risk of adverse effects. One of these methods involves delivering the toxic chemotherapeutic agent to the site of the cancer by injecting it directly into an artery. However, no organ absorbs all the cytotoxic compound on the first pass, and much of the anticancer drug is left to circulate through the body and affect normal cells. In the case of metastatic colorectal cancer in the liver, the attempt to deliver drugs directly to the cancer has taken a step further. Tiny microcapsules made of ethylcellulose and polyethylene can be constructed to contain the anticancer agent mitomycin C. When these microcapsules are injected into the hepatic artery, the liver actively works to remove them, as a part of the liver's normal job as chemical processor for the body and blood. In an evaluation of microencapsulated mitomycin C, researchers have shown that the novel delivery system carries an unusually high proportion of drug into the liver, and as a consequence, reduces the exposure of the rest of the body to this toxic substance. In a study involving six patients, the peak blood concentration of mitomycin C was 10 times less when it was given as a microcapsulated preparation than when given as a free drug. The clearance of the microcapsulated drug from the blood was more rapid. Because the side effects of the treatment are likely to be related to the blood levels of the drug, greater and more effective doses of mitomycin C microcapsules may become practical. However, the method still requires further study, as the microcapsules may block the catheter through which they are injected. The disposable catheters used in this pharmacokinetic evaluation to preempt possible blockage may not be practical in the routine treatment of patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Reports, Dosage and administration, Cancer invasiveness, Drug targeting

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Continuous intrahepatic infusion of floxuridine and leucovorin through an implantable pump for the treatment of hepatic metastases from colorectal carcinoma

Article Abstract:

Colorectal cancer is a major killer in Western nations; in roughly 60 percent of advanced colorectal cancer, metastatic tumors have spread to the liver. Conventional chemotherapy is not effective against these metastases, and rarely results in a response rate over 30 percent. It was proposed that a feature of the liver circulation might be used to improve chemotherapy for liver metastases. The majority of liver metastases receive their blood supply from the hepatic artery. Therefore, it may be possible to deliver increased doses of chemotherapeutic drugs to the tumors by direct infusion of drugs into the hepatic artery. An alternating infusion of two weeks of a combination of drugs, followed by two weeks of saline solution was used to treat 24 patients with colorectal cancer with liver metastases. The first eight patients were treated with 0.3 milligrams per meter squared of body area per day of floxuridine and 30 milligrams per meter squared per day of leucovorin. This dose produced a response in all patients, but gall bladder inflammation was observed in two patients, and the dosage was reduced for the seven following patients. A one third reduction in the floxuridine dose eliminated the biliary sclerosis seen previously, but only four of seven patients achieved partial responses. An attempt was made to use the higher dose on a one-week alternating schedule, rather than the original two-week timetable; only six of nine patients achieved a partial response, and sclerosing cholangitis, inflammation of the bile ducts with a harding of the tissue, developed in three of nine patients. The overall response rate was 72 percent, and 18 of 25 patients were alive after one year. Although more patients must die before the average survival may be determined, the average survival will be at least 27 months. The results indicate that the infusion of floxuridine and leucovorin is effective in the treatment of colorectal cancers that have spread to the liver, but that the liver toxicity is high, and may be higher than that previously reported for floxuridine therapy alone. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Infusion therapy, Floxuridine

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Intrahepatic mitomycin C as a salvage treatment for patients with hepatic metastases from colorectal carcinoma

Article Abstract:

Colorectal cancer is cancer of the large intestine and rectum. The spread of cancer cells to the liver, hepatic metastasis, can be present at the time of diagnosis or develop later if the disease progresses. The hepatic metastasis of some patients does not respond well to commonly used chemotherapeutic drugs such as fluorodeoxyuridine (FUDR). In addition, some patients receiving chemotherapy drugs may become resistant to therapy or experience toxic side effects. Another chemotherapeutic drug, mitomycin C, was infused into the liver (intrahepatic) in 64 patients with hepatic metastasis. A partial response to mitomycin C was found in 11 patients (17 percent) and the disease was stabilized in another 10 (16 percent). The hepatic metastasis response rate to mitomycin C was 47 percent in patients who had a previous course of intrahepatic FUDR and 75 percent in patients who had to switch from FUDR because of a toxic reaction (did not complete a full course of FUDR therapy). The response rate was lower in patients who did not respond well to FUDR (13 percent) or were switched from FUDR because of disease progression (27 percent). The average survival rate was nine months from the onset of mitomycin C therapy. The use of intrahepatic mitomycin C in patients with hepatic metastasis of colorectal cancer offered some palliative benefit, particularly in patients having an initial response with FUDR chemotherapy. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cancer

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