Gastrointestinal cancer research : GCR最新文献

Background: Flavopiridol, a Cdk inhibitor, potentiates irinotecan-induced apoptosis. In a phase I trial of sequential irinotecan and flavopiridol, 2 patients with advanced hepatocellular carcinoma (HCC) had stable disease (SD) for ≥14 months. We thus studied the sequential combination of irinotecan and flavopiridol in patients with HCC.

Methods: Patients with advanced HCC naïve to systemic therapy, Child-Pugh ≤B8, and Karnofsky performance score (KPS) ≥70% received 100 mg/m(2) irinotecan followed 7 hours later by flavopiridol 60 mg/m(2) weekly for 4 of 6 weeks. The primary end point was an improvement in progression-free survival at 4 months (PFS-4) from 33% to 54%, using a Simon's two-stage design. Tumors were stained for p53.

Results: Only 16 patients in the first stage were enrolled: median age, 64 years; median KPS, 80%; Child-Pugh A, 87.5%; and stage III/IV, 25%/75%. The primary end point was not met; PFS-4 was 20%, leading to early termination of the study. Ten patients were evaluable for response: 1 had SD >1 year and 9 had disease progression. Grade 3 fatigue, dehydration, diarrhea, neutropenia with or without fever, lymphopenia, anemia, hyperbilirubinemia, and transaminitis occurred in ≥10% of the patients. Of the 9 patients who progressed, 5 had mutant p53 and 4 had wild-type p53. The patient with stable disease had wild-type p53.

Conclusion: Sequential irinotecan and flavopiridol are ineffective and poorly tolerated in patients with advanced HCC. Despite our limited assessments, it is possible that the presence of wild-type p53 is necessary but not sufficient to predict response in HCC.

Background: Colorectal cancer (CRC) is the most frequently diagnosed cancer among Alaska Native (AN) people, and the second leading cause of cancer death. The incidence rate for the combined years 1999 through 2003 was 30% higher than the rate among U.S. whites (USWs) for the same period. Current incidence rates may serve to monitor the impact of screening programs in reducing CRC in the AN population.

Methods: Incidence data are from the Alaska Native Tumor Registry and the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. We compared AN CRC incidence, survival rates, and stage at diagnosis with rates in USWs for cases diagnosed from 2005 through 2009. Relative survival calculations were produced in SEER*Stat by the actuarial method.

Results: The CRC age-adjusted incidence rate among AN men and women combined was higher than those in USW men and women (84 vs. 43/100,000; P < .05; AN:USW rate ratio [RR] = 2.0). The greatest differences between rates in AN people and USWs were for tumors in the hepatic flexure (RR = 3.1) and in the transverse (RR = 2.9) and sigmoid (RR = 2.5) regions of the colon. Rectal cancer rates among AN people were significantly higher than rates in USWs (21 vs.12/100,000). Five-year relative survival proportions by stage at diagnosis indicate that the CRC 5-year relative survival was similar in AN people and USWs for the period 2004 through 2009.

Conclusions: The high rate of CRC in AN people emphasizes the need for screening programs and interventions to reduce known modifiable risks. Research in methods to promote healthy behaviors among AN people is greatly needed.

Background: The aim of this phase 2 study was to evaluate the safety and efficacy of ixabepilone plus cetuximab in patients with advanced pancreatic cancer.

Methods: Eligible patients had advanced pancreatic adenocarcinoma that was metastatic or not amenable to resection, a Karnofsky performance status ≥70%, and no prior therapy for advanced disease. Patients received ixabepilone 32 mg/m(2) (3-hour IV infusion) every 3 weeks and cetuximab 250 mg/m(2) (1-hour IV infusion) weekly. The primary efficacy end point was the 6-month survival rate. Secondary end points included tumor response rate, overall survival, progression-free survival, and tolerability.

Results: A total of 54 patients were enrolled on this study. The 6-month survival rate was 57% (31/54: 95% CI: 43-71%) with a median overall survival of 7.6 months (95% CI: 5.5-12.2 months). Patients who developed acneiform rash (n = 36) had a median survival of 8.8 months, compared with 2.6 months for those without rash (n = 18). Of 31 patients with measurable disease (defined as response-evaluable), 4 had confirmed partial responses and an additional 24 had stable disease. The combination was generally well-tolerated with the most common grade 3/4 hematological toxicities being leucopenia (39%) and neutropenia (33%). The most common grade 3/4 nonhematologic toxicity was fatigue (17%).

Conclusions: The combination of ixabepilone and cetuximab was active and had acceptable toxicity. The efficacy results are similar to single-agent ixabepilone and gemcitabine-based combination therapies in patients with advanced pancreatic cancer. Exploratory analyses suggest a trend toward improved survival for patients who experienced rash.