Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial.
BACKGROUND
A standard second-line chemotherapy regimen has yet to be defined for patients with gemcitabine (Gem)-refractory advanced pancreatic cancer (PC).


METHODS
In this multicenter phase II trial, patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen received pemetrexed 500 mg/m(2) as a 10-min infusion every 3 weeks until disease progression or occurrence of unacceptable toxicity. The primary end point was the 3-month survival rate.


RESULTS
A total of 192 treatment cycles were given to 52 patients. The overall response rate was 3.8% (two partial responses); 10 patients (19.2%) experienced stable disease, nine of them for >12 weeks. At least one CA 19-9 reduction > or =50% occurred in 12 patients (23.1%). The 3-month survival rate was 75% (95% confidence interval 63.2% to 86.8%), the median time to tumor progression was 7 weeks (range 1-62 weeks) and the median overall survival time was 20 weeks (range 1-84 weeks). Grade 3/4 hematological toxic effects included (percent of patients): neutropenia (17.3%), thrombocytopenia (5.8%) and anemia (3.8%). The most frequent non-hematological toxic effects were diarrhea, nausea and stomatitis/pharyngitis (23.1% each).


CONCLUSIONS
Pemetrexed is a safe treatment option with moderate activity in patients with advanced PC after failure of Gem.
Boeck
S
S
Department of Internal Medicine III, University Hospital Grosshadern, Ludwigs-Maximilians University, Marchioninistrasse 15, D-81377 Munich, Germany.
Weigang-Köhler
K
K
Fuchs
M
M
Kettner
E
E
Quietzsch
D
D
Trojan
J
J
Stötzer
O
O
Zeuzem
S
S
Lordick
F
F
Köhne
C-H
CH
Kröning
H
H
Steinmetz
T
T
Depenbrock
H
H
Heinemann
V
V
D000328:Adult; D000368:Aged; D018395:CA-19-9 Antigen / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000068437:Pemetrexed; D015996:Survival Rate; D017211:Treatment Failure; D000093542:Gemcitabine
D018395:CA-19-9 Antigen; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine