Phase II trial to evaluate gemcitabine and etoposide for locally advanced or metastatic pancreatic cancer.
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.
Melnik
Marianne K
MK
Grand Rapids Clinical Oncology Program, Michigan State University, East Lansing, Michigan, USA. marianne.melnik@grcop.org
Webb
Craig P
CP
Richardson
Patrick J
PJ
Luttenton
Charles R
CR
Campbell
Alan D
AD
Monroe
Thomas J
TJ
O'Rourke
Timothy J
TJ
Yost
Kathleen J
KJ
Szczepanek
Connie M
CM
Bassett
Michelle R
MR
Truszkowski
Kimberly J
KJ
Stein
Phyllis
P
Van Brocklin
Matthew W
MW
Davis
Alan T
AT
Bedolla
Gabriela
G
Vande Woude
George F
GF
Koo
Han-Mo
HM
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
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005047:Etoposide; D000093542:Gemcitabine