Hematological toxicity of combined 177Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up.
BACKGROUND
The combination of radiopeptide therapy [peptide receptor radionuclide therapy (PRRT)] with radiosensitizing chemotherapy of gastroenteropancreatic neuroendocrine tumors (GEP NETs) may improve efficacy, but has the potential to increase myelotoxicity. In a prospective clinical study of GEP NET patients treated with (177)Lu-octreotate PRRT in combination with capecitabine and temozolomide, as a prelude to a planned Australasian Gastro-Intestinal Trials Group (AGITG) international randomized controlled trial, we characterized the incidence and degree of hematological toxicity.


METHODS
Well-differentiated progressive metastatic GEP NETs in 65 patients were treated with 4 cycles of 7.8 GBq (177)Lu-octreotate, 1,650 mg/m(2) capecitabine (n = 28) and 1,500 mg/m(2) capecitabine with 200 mg/m(2) temozolomide (n = 37), and monitored for hematological toxicity over a 5-year period.


RESULTS
Short-term, self-limited hematological toxicity grade 3/4 comprised anemia in 1 patient (3.5%) in the 28 patient-cohort of patients treated with (177)Lu-octreotate and capecitabine. One of these patients (3.5%) later developed significant anemia and one developed thrombocytopenia (3.5%) over a median follow-up of 60 months (SD 20). The incidence of short-term grade 3/4 reversible myelosuppression in 37 patients after (177)Lu-octreotate/capecitabine/temozolomide was zero. Long- term follow-up for a median of 36 months (SD 11) showed significant thrombocytopenia in 2.7% and neutropenia in 2.7% of the patients and anemia in 10.8% of the patients (n = 4). The 3-year median hemoglobin and platelet and neutrophil counts trended downwards, but remained within normal ranges. Two patients in this cohort developed myelodysplastic syndrome.


CONCLUSIONS
The modest reversible hematological toxicity of PRRT of GEP NETs is not significantly increased by the addition of radiosensitizing chemotherapy with capecitabine and temozolomide in combination with (177)Lu-octreotate, which has the potential to enhance the efficacy of radiopeptide therapy.
Department of Hematology, Fremantle Hospital, The University of Western Australia, Fremantle, W.A., Australia.
Murali
M
Kesavan
Phillip G
PG
Claringbold
J Harvey
JH
Turner
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D000069287:Capecitabine; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004067:Digestive System Neoplasms / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D015994:Incidence; D007414:Intestinal Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy*; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D016896:Treatment Outcome
C554548:177Lu-octreotate; D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D003841:Deoxycytidine; D000069287:Capecitabine; D003606:Dacarbazine; D015282:Octreotide; D005472:Fluorouracil; D000077204:Temozolomide