A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer.
BACKGROUND
Pomalidomide is an investigational immunomodulating drug (IMiD) that also inhibits angiogenesis and has direct anti-tumour effects. This phase I study was performed to identify the optimal dose of pomalidomide to be used in combination with gemcitabine in the treatment of patients with metastatic pancreatic cancer.


METHODS
Eligible patients had histologically documented metastatic adenocarcinoma of the pancreas. No prior gemcitabine for metastatic disease or for primary treatment of locally advanced disease was allowed although prior radiation therapy with 5-flourouracil (5-FU) or gemcitabine as a radiosensitizer was allowed. All patients received gemcitabine 1000 mg/m(2) IV on days 1, 8 and 15 of a 28 day cycle. Pomalidomide was administered orally on days 1-21 at doses escalated from 2 to 10mg daily. Patients were re-evaluated every 8 weeks; treatment continued until disease progression or intolerable toxicity occurred.


RESULTS
Twenty-three patients were enrolled with a median age of 62 and Eastern Cooperative Oncology Group (ECOG) performance status 0 (87%) and 1 (13%). The maximum tolerated dose (MTD) was 10mg/day on days 1-21. Neutropaenia was the most common grade 3/4 toxicity (38%); other grade 3/4 toxicity included deep vein thrombosis (DVT) (22%) and anaemia (9%). While efficacy was not a primary end-point of this study, 3 of 20 evaluable patients (15%) had partial responses and 10 patients (50%) had >50% decrease in CA 19-9 levels.


CONCLUSIONS
The combination of pomalidomide and gemcitabine was feasible and safe in most patients receiving first-line chemotherapy for metastatic pancreatic cancer. Neutropaenia, the dose-limiting toxicity, was brief and reversible. Intermittent dosing of pomalidomide allowed substantially higher doses than were previously reported with a continuous schedule. This combination merits further evaluation in the treatment of metastatic pancreatic cancer.
Sarah Cannon Research Institute, Nashville, TN 37203, USA. jinfante@tnonc.com
Jeffrey R
JR
Infante
Suzanne F
SF
Jones
Johanna C
JC
Bendell
David R
DR
Spigel
Denise A
DA
Yardley
Colin D
CD
Weekes
Wells A
WA
Messersmith
John D
JD
Hainsworth
Howard A
HA
Burris
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D013792:Thalidomide; C467566:pomalidomide; D000093542:Gemcitabine