Phase II trial of gemcitabine plus irinotecan in patients with esophageal cancer: a Southwest Oncology Group (SWOG) trial.
OBJECTIVE
Metastatic esophageal carcinoma is an incurable disease with median survival duration of 6 to 8 months. Based on preclinical data suggesting a dose-dependent synergy between gemcitabine and irinotecan we have conducted a phase II trial in patients with advanced or metastatic esophageal carcinoma.


METHODS
Patient eligibility included a diagnosis of squamous cell or adenocarcinoma of the esophagus/gastroesophageal (GE) junction, metastatic or recurrent disease, no CNS metastasis, no prior chemotherapy, prior adjuvant/neoadjuvant chemotherapy was allowed, no prior gemcitabine or irinotecan, performance status of 0 to 2 and adequate organ function. Patients received gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 given day 1 and day 8, every 3 weeks. The primary end point was the 6-month survival rate. The secondary end point was to assess qualitative and quantitative toxicities.


RESULTS
Fifty-seven eligible patients were accrued. There were 4 treatment-related deaths. The primary grade 3 to 4 toxic events were diarrhea, dehydration, neutropenia, thrombocytopenia, anemia, and anorexia; and 4 episodes of grade 3 to 5 febrile neutropenia, 1 fatal. The study was designed to detect a difference between the null hypothesis of 30% 6-month survival and the alternative hypothesis of 50% 6-month survival. The Kaplan-Meier estimate of 6-month survival is 56% (95% CI: 43-69%), with a median of 6.3 months. The median time to progression was 3.7 months. The 6-month progression-free survival estimate is 25% (95% CI: 13-36%).


CONCLUSIONS
The length of survival suggests that this combination has benefit similar to platinum containing regimens, however, the toxicity is substantial and is unlikely to prove superior to platinum containing regimens.
Williamson
Stephen K
SK
University of Kansas Medical Center, Kansas City, KS, USA. swilliam@kumc.edu
McCoy
Sheryl A
SA
Gandara
David R
DR
Dakhil
Shaker R
SR
Yost
Kathleen J
KJ
Paradelo
Jorge C
JC
Atkins
James N
JN
Blanke
Charles D
CD
Abbruzzese
James L
JL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine