Doxorubicin Beads in Treating Patients With Unresectable Liver Metastases From Neuroendocrine Tumors

OBJECTIVES:

Primary

- To gather preliminary data and determine the feasibility of a randomized study of
patients with unresectable hepatic neuroendocrine metastases using PVA microporous
hydrospheres/doxorubicin hydrochloride.

OUTLINE: A catheter is placed into the right or left hepatic artery. Patients with unifocal
tumors will have the catheter or microcatheter placed more selectively into the 2nd or 3rd
order branch off the right or left hepatic artery in closer proximity to the tumor. PVA
microporous hydrospheres/doxorubicin hydrochloride mixture is injected into the delivery
area.

Patients with less than 75% necrosis at 1 month undergo a second (and possibly a third a
month later) chemoembolization.

After completion of study therapy, patients are followed at 1 month, every 2 months for 1
year, and then every 3 months for 1 year.

DISEASE CHARACTERISTICS:

Inclusion criteria:

- Diagnosis of hepatic neuroendocrine metastases not suitable for radical therapies
(e.g., resection or liver transplantation)

- Histologically proven neuroendocrine tumor

- Tumors are hypervascular based on visual estimation by investigator

- Predominant to the liver disease, but extrahepatic disease is not an exclusion

- No predominant extrahepatic liver disease

- No significant life-threatening extrahepatic disease, in the judgment of the
physician

- Recent-interval progression of hepatic liver metastases

- No diffuse hepatic neuroendocrine metastases defined as massive ill-defined tumor
involvement measuring > 90% tumor burden

Exclusion criteria:

- Clinically evident ascites (a radiographic finding of trace ascites on imaging is
acceptable)

- Complete occlusion of the entire portal venous system

- Evidence of cirrhosis or portal hypertension

- Vascular resistance peripheral to the feeding arteries precluding passage of PVA
microporous hydrospheres/doxorubicin hydrochloride

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-2

- Must have preserved liver function (Child-Pugh class A-B) without significant liver
decompensation

- No advanced liver disease (e.g., Child-Pugh C class or active gastrointestinal
bleeding, encephalopathy, or ascites [trace ascites is acceptable]), meeting the
following criteria:

- Bilirubin > 3 mg/dL

- AST, ALT, and alkaline phosphatase > 5 times upper limit of normal

- Serum creatinine > 2.0 mg/dL

- Albumin ≤ 2.0 g/dL

- No vascular anatomy or blood that precludes catheter placement or emboli injection

- No presence of arteries supplying the lesion not large enough to accept PVA
microporous hydrospheres/doxorubicin hydrochloride

- No collateral vessel pathways potentially endangering normal territories during
embolization

- No feeding arteries smaller than distal branches from which they emerge

- Not pregnant

Exclusion criteria:

- See Disease Characteristics

- Another active primary tumor

- Any contraindication for hepatic embolization procedures, including any of the
following:

- Porto-systemic shunt

- Hepatofugal blood flow

- Impaired clotting tests (i.e., platelet count < 50,000/mm³, INR ≥ 1.8, or PTT ≥
39 seconds)

- Renal failure

- Severe peripheral vascular disease precluding catheterization

- Any contraindication for doxorubicin hydrochloride administration (i.e., serum
bilirubin > 5 mg/dL or leukocyte count < 1,500 cells/mm³)

- Allergy to contrast media

- Intolerant to occlusion procedures

- Presence of end arteries leading directly to cranial nerves

- Presence or likely onset of hemorrhage

- Presence of severe atheromatous disease

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

- Prior anticancer therapy for hepatic neuroendocrine metastases, except previous
surgical therapy

- Any continuing complication or prior cancer therapy that has not improved or resolved
prior to 21 days before start of treatment, if the investigator determines that the
continuing complication will compromise the safety of the patient after treatment
with PVA microporous hydrospheres/doxorubicin hydrochloride

- Presence of patent extra-to-intracranial anastomoses or shunts

- Use of PVA microporous hydrospheres/doxorubicin hydrochloride in the following
applications:

- Embolization of large-diameter arteriovenous shunts

- Pulmonary arterial vasculature

- Any vasculature where the use of PVA microporous hydrospheres/doxorubicin
hydrochloride could pass directly into the internal carotid artery or the
above-listed vessels

- Concurrent enrollment in another clinical study