re: Phil's pump Can anyone help me with medical translation on this??

[Guest guest]

Other than knowing that a break will be good for him to take a break this

sounds really technical. A summary or translation would be appreciated if you

have that type of knowledge

THanks

Toxicity of Hepatic Arterial FUDR Infusion

The most common problems with HAI are hepatic toxicity and ulceration of the

stomach and duodenum. Myelosuppression, nausea, vomiting, and diarrhea do

not occur with HAI of FUDR. If diarrhea does occur, shunting to the bowel

should be suspected. _119_ (javascript:PopUpMenu2_Set(Menu_id2945304)

Clinically, biliary toxicity is manifested as elevations of aspartate

transaminase

(AST), alkaline phosphatase, and bilirubin. In the early stages of toxicity,

hepatic enzyme elevations will return to normal when the drug is withdrawn and

the patient is given a rest period, while in more advanced cases, it does not

resolve. The bile ducts derive their blood supply almost exclusively from the

hepatic artery _120_ (javascript:PopUpMenu2_Set(Menu_id2945328) and thus

are undoubtedly perfused with high doses of chemotherapy.

In patients who develop jaundice, an endoscopic retrograde

cholangiopancreatogram (ERCP) may demonstrate lesions resembling idiopathic

sclerosing

cholangitis in 5 to 29% of patients treated by experienced clinicians. _121_

(javascript:PopUpMenu2_Set(Menu_id2945348) Since the ducts are sclerotic and

nondilated, sonograms usually do not show dilation. The strictures may be focal

and present at the hepatic duct bifurcation, and therefore drainage procedures

either by ERCP or by transhepatic cholangiogram may be helpful. Duct

obstruction from metastases should first be excluded by CT of the liver.

Close monitoring of liver function tests is necessary to avoid biliary

complications. If the serum bilirubin becomes 3 mg/dL, no further treatment

should

be given until the bilirubin returns to normal, and then only after a long

rest period, to prevent the development of sclerosing cholangitis.

Ulcer disease results from inadvertent perfusion of the stomach and duodenum

with drug via the small collateral branches from the hepatic artery and can

be prevented by careful dissection of these collaterals at the time of pump

placement. _122_ (javascript:PopUpMenu2_Set(Menu_id2945374)

(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed.section.23707#top)

New Approaches to Decrease Hepatic Toxicity

Three approaches have been tried to decrease hepatic toxicity: (1) HAI

dexamethasone (D), (2) circadian modification, and (3) HAI FU alternating with

FUDR. The hepatic toxicity induced by hepatic arterial infusion of FUDR may be

related to portal triad inflammation, which could lead to ischemia of the bile

ducts. Hepatic arterial administration of dexamethasone may decrease

inflammation and thereby decrease biliary toxicity. In patients with

established

hepatobiliary toxicity from HAI, dexamethasone promotes resolution of the liver

function abnormalities. In a randomized study of FUDR with D versus FUDR

alone, there was a trend toward decreased bilirubin elevation in patients

receiving FUDR + D compared with the group receiving FUDR alone (9% versus 30%,

p =

..07). _92_ (javascript:PopUpMenu2_Set(Menu_id2945499) Although the

addition of dexamethasone was not associated with the ability to administer a

significant increase in the amount of FUDR, the response rate with FUDR + D was

71% versus 40% for FUDR alone (p = .03). Survival was also improved: 23 months

for FUDR + D versus 15 months for FUDR alone.

The use of circadian modification of HAI of FUDR is another method to

decrease hepatic toxicity. In a nonrandomized study at the University of

Minnesota,

_123_ (javascript:PopUpMenu2_Set(Menu_id2945532) a comparison of constant

(flat) infusion versus circadian-modified (CM) hepatic arterial FUDR

infusion was conducted in 50 patients with metastatic colorectal carcinoma. The

initial dose was 0.25 to 0.3 mg/kg/d for a 14-day infusion. The group with

circadian modification received 68% of each daily dose between 3:00 p.m. and

9:00

p.m. The patients with CM infusion tolerated almost twice the daily dose of

FUDR with a decrease in hepatic toxicity compared with patients receiving flat

infusions. Unfortunately, the study was not randomized.

The third approach is to decrease toxicity by alternating drugs such as HAI

FUDR with hepatic arterial (HA) FU. Weekly HA bolus of FU does not cause

hepatobiliary toxicity; however, it frequently produces treatment-limiting

systemic toxicity or arteritis. Stagg and colleagues _124_

(javascript:PopUpMenu2_Set(Menu_id2945565) used alternating HAI of FUDR 0.1

mg/kg/d × 7 days

followed by HA bolus FU 15 mg/kg on days 14, 21, and 28 via the pump side port

every 35 days. _124_ (javascript:PopUpMenu2_Set(Menu_id2945662) The response

rate was 51%, and median survival was 22.4 months. In contrast to the

experience with single-agent HAI of FUDR, no patient has had treatment

terminated

because of drug toxicity. Metzger and colleagues _125_

(javascript:PopUpMenu2_Set(Menu_id2945602) using an infusion of FU and

mitomycin-C, found that

median survival was 18 months with a partial response rate of 57% in his

patients.

Sclerosing cholangitis did not occur, but mucositis and leukopenia did.

Catheter complications occurred, which led to premature termination of

treatment

in one-third of the patients. and colleagues _126_

(javascript:PopUpMenu2_Set(Menu_id2945623) using HAI of FU and intravenous

LV saw no

responses in 10 patients. Warren treated 35 patients with HAI of FU and

systemic

LV. The response rate was 48%, and the median survival was 19 months. _127_

(javascript:PopUpMenu2_Set(Menu_id2945637) Though the dose of FUDR fits into

an implanted pump, the dose of FU requires an external pump for infusion or

bolus weekly side port injections.

(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed.section.23707#top)