title: Phase II trial to evaluate gemcitabine and etoposide for locally advanced or metastatic pancreatic cancer.
abstract: Prior studies suggest that tumor cell lines harboring RAS mutations display remarkable sensitivity to gemcitabine and etoposide. In a phase II clinical trial of patients with locally advanced or metastatic pancreatic cancer, we evaluated the response rate to a combination of these drugs. Forty chemo-naïve patients with nonresectable and histologically confirmed pancreatic cancer were accrued. Patients received gemcitabine 1,000 mg/m(2) (days 1 and 8) and etoposide 80 mg/m(2) (days 8, 9, and 10; 21-day cycle). The primary end point was radiological response rate. Secondary objectives were determination of overall survival, response duration (time to progression), quality of life, toxicity, and CA 19-9 biomarker response. In 35 evaluable patients, 10 exhibited a radiological partial response and 12 had stable disease in response to treatment. Twenty patients exhibited a >20% decrease in CA 19-9 biomarker levels. Median overall survival was 6.7 months for all patients (40) and 7.2 months for evaluable patients (35). Notably, four patients survived for longer than 1 year, with two patients surviving for more than 2 years. Median time to progression for evaluable patients was 3.1 months. The median overall survival for locally advanced patients was 8.8 months and 6.75 months for metastatic patients. One-year survival was 10% for all patients and 11.4% for evaluable patients. Quality of life improved in 12 patients and remained stable in 3 of the evaluable patients. The primary dose-limiting toxicities were hematologic toxicity and fatigue. These results show that the gemcitabine and etoposide combination is generally well-tolerated and exhibits a response rate similar to other published studies.
authors.affiliation: Grand Rapids Clinical Oncology Program, Michigan State University, East Lansing, Michigan, USA. marianne.melnik@grcop.org
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Melnik
authors.forename: Craig P
authors.initials: CP
authors.lastname: Webb
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Richardson
authors.forename: Charles R
authors.initials: CR
authors.lastname: Luttenton
authors.forename: Alan D
authors.initials: AD
authors.lastname: Campbell
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Monroe
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: O'Rourke
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Yost
authors.forename: Connie M
authors.initials: CM
authors.lastname: Szczepanek
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Bassett
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Truszkowski
authors.forename: Phyllis
authors.initials: P
authors.lastname: Stein
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Van Brocklin
authors.forename: Alan T
authors.initials: AT
authors.lastname: Davis
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bedolla
authors.forename: George F
authors.initials: GF
authors.lastname: Vande Woude
authors.forename: Han-Mo
authors.initials: HM
authors.lastname: Koo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005047:Etoposide; D000093542:Gemcitabine