Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors.
Abstract We conducted a phase I-II clinical trial to assess the safety and efficacy of combining lutetium-177 ((177)Lu)-octreotate with capecitabine and temozolomide in treating advanced low-grade neuroendocrine tumors (NETs). All 35 patients received fixed activities of 7.8 GBq (177)Lu-octreotate each 8 weeks, with 14 days of capecitabine 1500 mg/m(2) for 4 cycles. In phase I, successive cohorts of patients received escalating doses of temozolomide in groupings of 100, 150, and 200 mg/m(2) in the last 5 days of each capecitabine cycle. In phase II, patients were treated with 200 mg/m(2) temozolomide. Treatment was well tolerated in all dosage groups. No dose-limiting grade 2, 3, or 4 toxicities were seen in cohorts 1 (100 mg/m(2)) or 2 (150 mg/m(2)). Twenty-eight patients completed treatment at the 200 mg/m(2) temozolomide level. Adverse events were mild to moderate. The commonest toxicities were transient nausea grade 2 (18%), grade 3 (3%), thrombocytopenia grade 2 (24%), and neutropenia grade 3 (6%). There were no grade 4 events. Thirty-four patients were evaluable for tumor response. Overall, complete response (CR) was achieved in 15% (95% CI 3-27); partial response (PR), in 38% (95% CI 22-55); stable disease (SD), in 38% (95% CI 22-55); and 3 patients failed to respond to treatment. Median progression free survival (PFS) was 31 months (95% CI 21-33), and median overall survival (OS) has not been reached with 90% surviving at 24 months follow-up (range 21-30). Overall objective response rate (ORR) in patients with gastroenteropancreatic NETs showed CR 16% (95% CI 3-28), PR 41% (95% CI 24-58), SD 37% (95% CI 21-54), and PD 6% (95% CI 0-15). Response rates were higher in patients with gastropancreatic NETs than in those with bowel primaries (enteric-NETs); CR 18% versus 13%, PR 64% versus 13%, SD 12% versus 67%. (177)Lu-octreotate, in combination with capecitabine and temozolomide, is well tolerated in patients with advanced low-grade NETs, and shows substantial tumor control rates.
Department of Oncology, Fremantle Hospital, The University of Western Australia, Australia.
Phillip G
PG
Claringbold
Richard A
RA
Price
J Harvey
JH
Turner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D000077204:Temozolomide; D016896:Treatment Outcome
C554548:177Lu-octreotate; D019275:Radiopharmaceuticals; D003841:Deoxycytidine; D000069287:Capecitabine; D003606:Dacarbazine; D015282:Octreotide; D005472:Fluorouracil; D000077204:Temozolomide