Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation.
OBJECTIVE
The combination of chemotherapy and immunotherapy has not been examined in patients with advanced pancreatic cancer. We conducted a study of two granulocyte macrophage colony-stimulating factor-secreting pancreatic cancer cell lines (CG8020/CG2505) as immunotherapy administered alone or in sequence with cyclophosphamide in patients with advanced pancreatic cancer.


METHODS
This was an open-label study with two cohorts: cohort A, 30 patients administered a maximum of six doses of CG8020/CG2505 at 21-day intervals; and cohort B, 20 patients administered 250 mg/m(2) of cyclophosphamide i.v. 1 day before the same immunotherapy given as in cohort A. The primary objective was to evaluate safety and duration of immunity. Secondary objectives included time to disease progression and median overall survival.


RESULTS
The administration of CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity. Median survival values in cohort A and cohort B were 2.3 and 4.3 months, respectively. CD8(+) T-cell responses to HLA class I-restricted mesothelin epitopes were identified predominantly in patients treated with cyclophosphamide + CG8020/CG2505 immunotherapy.


CONCLUSIONS
Granulocyte macrophage colony-stimulating factor-secreting pancreatic cancer cell lines CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity in patients with advanced pancreatic cancer. Also, mesothelin-specific T-cell responses were detected/enhanced in some patients treated with CG8020/CG2505 immunotherapy. In addition, cyclophosphamide-modulated immunotherapy resulted in median survival in a gemcitabine-resistant population similar to chemotherapy alone. These findings support additional investigation of cyclophosphamide with CG8020/CG2505 immunotherapy in patients with advanced pancreatic cancer.
Laheru
Dan
D
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Public Health, Baltimore, Maryland 21231, USA. laherda@jhmi.edu
Lutz
Eric
E
Burke
James
J
Biedrzycki
Barbara
B
Solt
Sara
S
Onners
Beth
B
Tartakovsky
Irena
I
Nemunaitis
John
J
Le
Dung
D
Sugar
Elizabeth
E
Hege
Kristen
K
Jaffee
Elizabeth
E
D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D015996:Survival Rate; D014018:Tissue Distribution
D018906:Antineoplastic Agents, Alkylating; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide