Lapatinib/gemcitabine and lapatinib/gemcitabine/oxaliplatin: a phase I study for advanced pancreaticobiliary cancer.
OBJECTIVE
To evaluate the safety/tolerability and potential antitumor activity of lapatinib, at dose ranges of 1000 to 1500 mg/d, in combination with gemcitabine and gemcitabine/oxaliplatin (GEMOX) in patients with advanced pancreaticobiliary cancer.


METHODS
Patients with advanced pancreaticobiliary cancer were assigned to 1 of 4 cohorts of lapatinib administered once daily. Toxicities, response, and survival were assessed.


RESULTS
Twenty-five patients were enrolled, 18 with pancreatic cancer and 7 with biliary cancer. Lapatinib, 1500 mg/d, was successfully administered with weekly gemcitabine. Dose limiting toxicities of nausea and anorexia occurred in 2 of 5 patients receiving 1500 mg/d lapatinib with GEMOX. The median survival of all patients was 11 months and the 1-year survival was 48%.


CONCLUSIONS
Lapatinib, 1500 mg/d, can be administered with weekly gemcitabine. The maximum tolerated dose of lapatinib is 1000 mg/d with GEMOX. A phase II study of lapatinib and gemcitabine for metastatic pancreatic cancer will be initiated.
Safran
Howard
H
Department of Medicine, The Miriam Hospital, Brown University Oncology Group, Providence, Rhode Island 02906, USA. hsafran@lifespan.org
Miner
Thomas
T
Resnick
Murray
M
Dipetrillo
Thomas
T
McNulty
Brendan
B
Evans
Devon
D
Joseph
Plakyil
P
Plette
Angela
A
Millis
Robin
R
Sears
Dina
D
Gutman
Ned
N
Kennedy
Teresa
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011799:Quinazolines; C431073:oxiplatin; D000077341:Lapatinib; D003841:Deoxycytidine; D000093542:Gemcitabine