Arsenic trioxide in patients with adenocarcinoma of the pancreas refractory to gemcitabine: a phase II trial of the University of Chicago Phase II Consortium.
OBJECTIVE
There is no effective therapy for patients with metastatic pancreatic cancer who fail initial therapy with gemcitabine. Arsenic trioxide has potent antiproliferative and proapoptotic effects in pancreatic cancer cell lines. We conducted a multicenter phase II trial in patients with advanced pancreatic cancer who experienced disease progression on or after a gemcitabine-containing regimen.


METHODS
Arsenic trioxide 0.3 mg/kg was administered intravenously over 1 hour daily for 5 consecutive days every 28 days. Restaging computed tomography scans were obtained every 2 cycles.


RESULTS
Thirteen patients were enrolled between December 2002 and November 2003. Twenty-four cycles were administered (median 2; range 1-2). There were no grade 3/4 hematologic toxicities; grade 1/2 anemia and leukopenia occurred in 50% and 25% of patients, respectively. Grade 3 toxicities included fatigue and thrombosis in 17% of patients. Only 1 patient developed a prolongation of the QTc interval. There were no objective responses. Median progression-free survival was 1.6 months (95% confidence interval, 1.2-1.9). Median survival was 3.8 months (95% confidence interval, 1.6-6.8).


CONCLUSIONS
Despite promising in vitro data, arsenic trioxide has no activity in pancreatic cancer patients who develop progressive disease after gemcitabine. Multicenter phase II trials are feasible in this patient population, and novel agents are clearly needed.
Kindler
Hedy Lee
HL
Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL 60637-1463, USA. hkindler@medicine.bsd.uchicago.edu
Aklilu
Mebea
M
Nattam
Sreenivasa
S
Vokes
Everett E
EE
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy; D010087:Oxides / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D003841:Deoxycytidine; D000077237:Arsenic Trioxide; D000093542:Gemcitabine