Intraarterial infusion chemotherapy has several theoretical advantages over conventional therapy for
the treatment of unresectable malignancies. However, the catheter problems and patient restriction to
the hospital associated with its use have resulted in infrequent application and a notable lack of progress
in this field of oncology. This paper describes the use of a totally implantable, percutaneously refillable
infusion pump in 5 patients with primary or metastatic carcinoma of the liver. The infusion cannulae
were placed into the hepatic arteries under direct vision at laparotomy, and the pumps were placed in
subcutaneous pockets. Four patients received infusions of 5-fluorodeoxyuridine at rates of 0.2-0.5 mg/
kg/day for periods of three to 29 weeks; the pump in the fifth patient was defective and was removed. The
implanted pumps were well tolerated in these subjects, who received chemotherapy as outpatients; the
only adverse effects noted were related to FUDR toxicity. This implantable infusion pump appears to be a
practical means of delivering long-term intraarterial infusion chemotherapy to outpatients.
Cancer 45866-869, 1980.
866
No. 5 INFUSION
CHEMOTHERAPY Buchwald et al. 867
7 9
\
PIG.2. Cross section of implantable infusion pump: 1 ) flow Restrictor: 2) silicone rubber coating: 3) bellows: 4) charging fluid chamber; 5 )
infusate chamber; 6 ) charging fluid fill tube (permanently sealed): 7) filter assembly; 8) inlet septum: 9) needle stop.
868 March I 1980
CANCER VOl. 45
Patient Follow- U p
I ('Cannula
I Results
The duration of intraarterial infusion chemotherapy
Ftc;. 3. Pump and cannulae placement for use in hepatic arterial for each patient is listed in Table 1. Total infusion
chemotherapy.
time ranged from five to 33 weeks with Patient 1 receiv-
ing 29 weeks of continuous FUDR infusion. All pa-
ml, calculated to deliver 0.20-0.50 mglkg body weight/ tients are dead at the time of this report. Five episodes
day into the hepatic artery at 1 mllday. After wound that were felt to represent FUDR toxicity were re-
healing was complete, the patients were allowed to corded, involving pancytopenia or nausea, vomiting,
return home, and continue their regular activities. They anorexia, and stomatitis. These symptoms cleared
rapidly when the FUDR in the pumps was replaced with
sterile water, and usually were preventcd when a lower
dose of drug was used subsequently. N o complications
relating specifically to the chronically implanted pumps
or delivery cannulae were noted, although the lack of
angiographic and autopsy data precludes conclusions
about hepatic artery patency or cannula thrombosis.
The continued flow through the delivery cannulae at all
times argues against hepatic artery occlusion. The fifth
pump, in Patient 5 , was defective and was removed in
less than 24 hours. Three of the four functional pumps
needed refills only about every 30 days; the fourth was
emptied after 16 days because FUDR toxicity de-
veloped in Patient 3 , and treatment was not resumed.
Discussion
The present results indicate that continuous, long-
term intraarterial infusion chemotherapy is practicable
in outpatients through the use of a totally implantable
- - infusion pump. The device was well tolerated by these
patients. They continued their normal daily activities
FIG.4. I n vivn refilling technique. A. Pump is being emptied by and returned for outpatient visits at approximately
puncturing the septum with a special needle and allowing pump's
pressure to force the remaining infusate into an empty syringe bar- monthly intervals, unless they sought attention for
rel. B. Fresh infusate is then injected into the pump's reservoir. another reason. We emphasize that their activities
No. 5 INFUSION CHEMOTHERAPY BuchwaEd et al. 869
were not limited in any way by the device, in con- A modification of the pump is being investigated to
trast to the percutaneous cannulae and carrying harnesses make pump operation even more versatile. A side port
necessary for currently available intra-arterial infu- with a second self-sealing septum added by the manu-
sion methods. facterer* to some experimental models was tested in
The purpose of this study was to determine whether our animal laboratory. These tests demonstrated that
the tested implantable infusion pump might be a useful bolus injections and angiography could be performed
means of providing intraarterial infusion chemotherapy through the delivery cannula while the pump was
in selected cancer patients. We did not intend to study implanted. This modification should facilitate intra-
the effect of FUDR infusion on hepatic malignancies. arterial infusion chemotherapy in future clinical studies.
The early deaths of 2 patients, and the progression of
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