Gemcitabine And Irinotecan In Patients With Previously Treated Carcinoma Of Unknown Primary Site: A Minnie Pearl Cancer Research Network Phase Ii Trial

4167 Background: Three sequential phase II trials done by the Minnie Pearl Cancer Research Network of taxane, platinum, and etoposide combinations for carcinoma of unknown primary site (CUP) have produced median survivals of about 10 months, and 1, 2, 3, 5, and 8-year survivals of 42%, 22%, 18%, 12%, and 10%, respectively. In an effort to improve efficacy, we evaluated second-line treatment with a new combination regimen of gemcitabine and irinotecan. Methods: The primary objective was to evaluate the toxicity and response rate in CUP as second-line therapy. Eligible patients (pts) had adenocarcinoma, poorly differentiated adenocarcinoma, poorly differentiated carcinoma, or poorly differentiated neuroendocrine carcinoma (PDNE); one prior chemotherapy regimen, not including recent irinotecan and/or gemcitabine; absence of brain metastasis; and adequate organ function. Gemcitabine 1000 mg/m2 IV days 1, 8 and irinotecan 100 mg/m2 IV days 1, 8 were given every 21 days. Pts with objective responses or stable tumor after 2 cycles (6 weeks) continued additional 3-week cycles for a recommended 6 cycles. Results: 31 pts were treated and 27 were evaluable for response; median age 50 years (range 24–74); performance status (0=1, 1=28, 2=2); men - 15; women - 16. The response rate was 15% with 3 (11%) partial responses, 1 (4%) complete response. 11 pts had stable disease and 12 progressive disease. Of the 2 pts with PDNE, both had stable disease. The median time-to-progression, median survival, and 1-year survival were 3.5 months, 4 months, and 15%, respectively. Grade 3/4 toxicities included: neutropenia (30%), thromobcytopenia (8%), diarrhea (8%), anemia (9%), neutropenic fever (3%), nausea/vomiting (8%), and fatigue (8%). Conclusions: Gemcitabine/irinotecan is an active and well-tolerated second-line treatment for pts with CUP. A randomized prospective phase III study of gemcitabine/irinotecan compared to paclitaxel/carboplatin/etoposide in the first-line setting is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly; Pfizer-Pharmacia