Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors.
Octreotide and everolimus have demonstrated efficacy in neuroendocrine tumors. Pasireotide is a somatostatin analog with binding affinity to a broader range of somatostatin receptor subtypes than octreotide. We performed a phase I study to evaluate the safety and feasibility of combining pasireotide with everolimus in patients with advanced neuroendocrine tumors. Cohorts of patients with advanced neuroendocrine tumors were treated with escalating doses of pasireotide (600-1200  μg s.c. b.i.d., followed by pasireotide LAR 40-60  mg i.m. monthly) and everolimus (5-10  mg daily). Twenty-one patients were treated. Dose-limiting toxicities consisting of grade 3 rash and grade 3 diarrhea were observed. Twelve patients were safely treated at the maximum protocol-defined dose level of pasireotide LAR 60  mg i.m. monthly and everolimus 10  mg daily. Hyperglycemia was common; other observed toxicities were consistent with the known toxicities of either agent alone. Partial tumor response was observed in one patient; 17 (81%) patients experienced at least some tumor regression as their best response to therapy. In conclusion, pasireotide LAR 60  mg i.m. monthly in combination with everolimus 10  mg daily is feasible and associated with preliminary evidence of antitumor activity in patients with advanced neuroendocrine tumors. Further studies evaluating this combination are warranted.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. jennifer_chan@dfci.harvard.edu
Jennifer A
JA
Chan
David P
DP
Ryan
Andrew X
AX
Zhu
Thomas A
TA
Abrams
Brian M
BM
Wolpin
Paige
P
Malinowski
Eileen M
EM
Regan
Charles S
CS
Fuchs
Matthew H
MH
Kulke
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D013004:Somatostatin; C517782:pasireotide; D000068338:Everolimus; D020123:Sirolimus