High-administered activity In-111 octreotide therapy with concomitant radiosensitizing 5FU chemotherapy for treatment of neuroendocrine tumors: preliminary experience.
BACKGROUND
High-administered activity In-111 octreotide (HA-Oc) therapy has been used for patients with disseminated neuroendocrine tumors (NET) with high somatostatin receptor (SSR) expression. Combining HA-Oc with radiosensitizing 5-fluorouracil (5FU) chemotherapy could enhance efficacy. Our other aim was to assess whether concomitant 5FU would contribute to significant additional toxicity.


METHODS
Fifteen (15) consecutive patients who received 3 cycles of HA-Oc+5FU were evaluated. Symptomatic, octreoscan, computed tomography (CT), hormonal responses, and toxicity were reviewed at 3 months post-last treatment. Long-term follow-up was performed to death or April 2008 to assess late toxicity and time to progression requiring retreatment.


RESULTS
At 3 months post-treatment, 67% of patients had symptomatic improvement, with 20% experiencing a complete resolution of symptoms. Overall, 90% achieved stabilization or a decrease in hormone levels. Octreoscan improvement/stabilization occurred in 95% and CT stabilization in 80% of patients with previously progressive disease, but no partial or complete regression by Response Evaluation Criteria in Solid Tumors criteria. Transient lymphopenia and nausea were the most common side-effects, and there was no significant renal or grade 4 hematologic toxicity. Subacute side-effects included a peripherally inserted central catheter line thrombosis (1 patient), discomfort/pain associated with lesion necrosis, and 1 lymph node swelling. Median time to retreatment was 23 months (range, 6-34) for 10 patients. Six (6) patients deceased (no deaths directly related to 5FU); 9 patients (60%) are alive at 36-139 months.


CONCLUSIONS
HA-Oc+5FU achieve a high rate of symptomatic response associated with stabilization/improvement in hormonal and functional scan abnormalities. Combination treatment achieved disease stabilization in the majority of patients with previously progressive disease. There was no significant observed increase in toxicity with additional 5FU, making it a promising adjunct to radiopeptide receptor therapy for progressive NET.
Kong
Grace
G
Center for Molecular Imaging, Peter MacCallum Cancer Center, East Melbourne, Victoria 3002, Australia.
Johnston
Val
V
Ramdave
Shakher
S
Lau
Eddie
E
Rischin
Danny
D
Hicks
Rodney J
RJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000532:radiotherapy*; D015282:Octreotide / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000096:biosynthesis; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
D007205:Indium Radioisotopes; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D015282:Octreotide; D005472:Fluorouracil