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Hepatic Artery Infusion pumps and how they work on those nasty mets

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It occurred to me that many if not most of you do not know what a Hepatic

Artery Infusion Pump is!

Basically it is inserted under the skin near the liver to deliver chemo

straight to those nasty liver mets and hopefully wipe them out completely. It

is

often, but always done following RFA (Radio Frequency Ablation).

RFA is a process that removes liver mets via a laser knife like process.

There are good links on the site and if you want/need more information I can go

digging. Bottom line is that in order to do RFA the mets have to be few in

number and take up no more than half of the liver.

Unfortunately Phil's mets are spread out all over his liver so they are

using the cart before the horse somewhat hoping the chemo reduces the mets so

they can later do surgery to remove the rest. If this works as well as

Oxaliplatin and Avastin did we will be looking at REMISSION.

For those who don't know the colon chemos dissolved Phil's 13 cm tumor so

that 18 months after diagnosis his colon was CLEAN!! On the last CT/PET scan

colon is still clean and the liver is stable and may in fact have areas of

DEAD tumor!!!!! YAHOOOOO!!!!

:

Anyway here is a description of the pump and how it works

Narice

BENEFITS

PATIENT SELECTION

RISKS

Treatment of hepatic metastases of colorectal cancer with HAI therapy has

been studied and extensively published on for more than a decade.3 While older

studies in HAI therapy reported mixed results in tumor response and survival

rates, new techniques, including the evolution of pharmacotherapeutic methods

and fully implanted drug delivery systems, make HAI therapy a viable option

for appropriately selected patients.5

BENEFITS

HAI therapy yields higher tumor response rates, delays progression

HAI therapy shows a trend toward increased survival rates

HAI therapy shows reduced systemic side effects

HAI therapy enhances quality of life

HAI therapy yields higher tumor response rates, delays progression

Several studies have demonstrated the efficacy of regional chemotherapy. One

early study (Table 1) showed a significant advantage in tumor response with

regional FUDR over systemic FUDR therapy.

n=99Regional

Fluorodeozyuridine

(FUDR)Systemic

(FUDR)

Complete tumor response

(p=0.001)20

Partial Response2310

Response rate53%21%

Table 1. Memorial Sloan Kettering Cancer Center Trial: Regional vs. systemic

FUDR infusion. Adapted from Kemeny.

Another study (Table 2) comparing the use of FUDR regionally and

systemically, showed a fourfold increase in overall tumor response and a delay

of tumor

progression with regional vs. systemic infusion. Some patients with

extrahepatic tumors were included in both groups.6 Since regional chemotherapy

would

have had virtually no effect on those tumors, regional chemotherapy results

may have been compromised unfavorably.

Numerous studies have shown improved tumor response and increased response

duration with regional chemotherapy over systemic administration.

n=143 Regional

(FUDR)Systemic

(FUDR)

Tumor response, complete8%5%

Tumor response, major (>50%)

(p=0.009)34%5%

total42%10%

Median time to progression, in days

(p=0.009)401201

Table 2. Northern California Oncology Group Trial: Randomized regional vs.

systemic infusion Adapted from Hohn

HAI therapy shows a trend toward increased survival

Several investigators have noted a trend toward increased survival rates

with HAI therapy.2,8 In two of the larger studies that demonstrate markedly

improved response rates, patient crossover from systemic chemotherapy to

regional

administration may have masked improved survival rates.2 A randomized study

of 100 patients showed " significant improvement in survival " in patients

receiving regional hepatic chemotherapy over those in a control group who

received supportive care.8

Figure 1. Survival rates: regional vs. systemic infusion. Adapted from

-Mersh.8

HAI therapy shows reduced systemic side effects

The high hepatic extraction of FUDR allows the use of greater dosages with

less risk of systemic toxicity.

Some patients who receive systemic chemotherapy for colorectal cancer

experience side effects, such as nausea, vomiting, diarrhea, etc. Generally,

patients receiving regional chemotherapy experience fewer side effects than

accompany systemic chemotherapy.5,6,9,10 Biliary toxicity has been a problem

with

regional chemotherapy, but has been largely avoided by changing the

chemotherapy regimen.

HAI therapy enhances quality of life

The demonstrated reduction in side effects with regional chemotherapy vs.

systemic chemotherapy can increase the patient's quality of life. Even with

progressive increase in hepatic tissue replacement, physical symptoms tended to

occur late in the course of the disease.

The development of fully implanted pumps allows the patient to be mobile and

reduces the need for frequent clinic visits for drug infusion. Further,

these pumps have an advantage over port access systems because they usually

require little or no home care, such as maintenance of the port. Patients often

can participate in activities of daily life as their illness permits with

little hindrance from side effects or administration of chemotherapy.

The Medtronic IsoMed and SynchroMed® Infusion Systems have been well studied

and approved for hepatic arterial infusion. For more information about

regional chemotherapy or Medtronic drug infusion systems, please contact your

Medtronic representative, or click here for additional contact information.

PATIENT SELECTION

Because liver metastases from colorectal cancer derive more than 80% of

their blood supply from the hepatic artery2, hepatic arterial infusion is well

suited as an alternative or an adjuvant to systemic chemotherapy for the

treatment of liver tumors. However, successful results depend on careful

patient

selection.

Candidates for HAI therapy should:

Have primary liver cancer or liver metastases from primary colorectal cancer

Show an absence of extra hepatic tumors

Have demonstrated portal vein patency

Be a suitable surgical candidate

Show no evidence of infection

Be willing to participate in frequent pump refill appointments

RISKS

In a recent study, complications with HAI therapy included pump pocket

infection6, arterial thromboses2, and catheter dislodgement. In this study, the

toxic effects of HAI therapy and systematic chemotherapy included neutropenia,

vomiting, nausea, and stomatitis. Patients receiving combined therapy

experienced more diarrhea than those receiving monotherapy. Other studies have

found

toxicity and side effects including chemical hepatitis, biliary sclerosis,

peptic ulcers, and gastritis/duodenitis10.

References

Goslin R, et al. Factors influencing survival in patients with hepatic

metastases from adenocarcinoma of the colon or rectum. Dis Colon Rectum.

25:749-754; 1982.

Venook AP. Update on hepatic intra-arterial chemotherapy. Oncology.

11(7):947-970;1997.

Durand-Zaleski I, et al, (For the Meta-Analysis Group in Cancer). Economic

implications of hepatic arterial infusion chemotherapy in treatment of

nonresectable colorectal liver metastases. J Natl Cancer Inst, 89(11):790-795;

1997.

Cohen AM, Schaeffer Higgins J. Treatment of metastatic colorectal cancer

with hepatic artery combination chemotherapy. Cancer. 57(6): 1115-1117; 1986.

Kemeny N, et al. Intrahepatic or systemic infusion of fluorodeoxyuridine in

patients with liver metastases from colorectal carcinoma. Ann Intern Med.

107:459-465;1987.

Hohn D, et al. A randomized trial of continuous intravenous versus hepatic

intra-arterial floxuridine in patients with colorectal cancer metastatic to

the liver: the northern California oncology group trial. J Clin Oncol.

7:1646-1654; 1989.

Wagman LD, et al, A prospective randomized evaluation of the treatment of

colorectal cancer metastatic to the liver. J Clin Oncol. 8(11):1885-1893;1990.

-Mersh TG, et al. Quality of life and survival with continuous

hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet.

344:1255- 1260;1994.

JK, Jr, et al. Intra-arterial floxuridine versus systemic

fluorouracil for hepatic metastases from colorectal cancer: A randomized trial.

Arch

Surg.125:1022;1990.

Chang AE, Schneider PD, Sugarbaker PH. A prospective randomized trial of

regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the

treatment of colorectal liver metastases. Ann Surg. 206:685-693;1987.

Kemeny, N., et al.; Randomized Study of Hepatic Arterial Infusion (HAI) and

Systemic Chemotherapy (SYS) Versus SYS Alone as Adjuvant Therapy After

Resection of Hepatic Metastases from Colorectal Cancer. New England Journal of

Medicine; 1999.

Site last updated on July 16, 2002

Version 1.07

© Medtronic, Inc. 2005

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