Predictors and significance of histologic response to neoadjuvant therapy for gastric cancer.

BACKGROUND: Perioperative therapy is the standard-of-care for locally-advanced gastric cancer but many patients do not respond. There are currently no known factors that predict response to therapy. METHODS: This was a retrospective study aimed to evaluate treatment effect grade (TEG) in patients with locally advanced gastric cancer treated with neoadjuvant therapy and surgery at a single center. Ordinal logistic regression was performed to identify predictors of TEG, scaled from 0 to 3. RESULTS: Fifty patients were identified. The majority were male (n = 33) and 50% were Hispanic. The most common regimens given were: 5-fluorouracil/leucovorin, oxaliplatin, and docetaxel (n = 23, 46%), epirubicin, cis- or oxaliplatin, and 5-fluorouracil/leucovorin or Xeloda (n = 8, 16%), and 5-fluorouracil/leucovorin and oxaliplatin (n = 9, 18%). Twenty-seven patients (55%) had complete or partial response to therapy (TEG 0-2), and 23 patients (46%) had no response (TEG 3). Of numerous variables analyzed, only race and SRC histology were associated with TEG. TEG was associated with disease free, but not disease specific survival. CONCLUSIONS: In this cohort, 46% of patients had no histologic response to therapy. SRC histology, and possibly race, should be considered in determination of optimal multidisciplinary regimens and in amount of therapy to be given upfront, as patients with SRC histology and those of non-Asian race are less likely to respond to standard regimens.

Systemic therapy of advanced pancreatic cancer: has the landscape changed?

Limited progress has been made in the treatment of advanced pancreatic cancer. Gemcitabine was established as a standard of care after a randomized phase III study showed an improvement in clinical benefit response and overall survival over 5-flurouracil. Multiple phase III studies have been conducted to improve upon the response and survival established with single-agent gemcitabine. Combining different cytotoxic chemotherapy with gemcitabine failed to provide any meaningful survival advantage over gemcitabine monotherapy. A modest improvement in overall survival was noted when an epidermal growth factor receptor tyrosine kinase inhibitor (erlotinib) was added to gemcitabine. The landscape for the treatment of advanced pancreatic cancer changed with the introduction of the fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) regimen at the 2010 American Society of Clinical Oncology meeting. The phase III clinical trial showed an overall survival improvement in the gemcitabine group of 6.8 months compared to 11.1 months in the FOLFIRINOX arm (P<.0001). More interestingly, almost half of the patients in the FOLFIRINOX group were alive after 1 year, and the response rate was 31.6%. A new triplet chemotherapy regimen has emerged to replace the use of single-agent gemcitabine in a highly selected patient population. In this article, we will review the published data on first-line chemotherapy, with discussion of targeted agents for advanced pancreatic cancer and potential future directions.