Gastrointestinal cancer research : GCR最新文献

Background: Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR). The primary goal of this phase I study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine when combined with cetuximab plus radiation in patients with locally advanced pancreatic cancer.

Patients and methods: Patients with locally unresectable adenocarcinoma of the pancreas were treated with gemcitabine (200 mg/m(2)/week before dose escalation) plus cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) concurrent with radiation (50.4 Gy).

Results: Nine patients were enrolled in the study. One withdrew due to declining performance status before receiving any therapy. Grade 4 allergic reactions to cetuximab caused the withdrawal of 2 patients. Another patient had elevated liver function test results and a stroke after his loading dose of cetuximab. Grade 3 or 4 toxicity developed in 3 of the remaining 5 patients treated with the level 1 dose. Therefore, no further dose escalations were planned. Grade 3 toxicities included nausea, vomiting, ileus, and pneumonitis. One patient had grade 4 diarrhea.

Conclusions: The combination of cetuximab, gemcitabine, and radiation resulted in significant toxicity. A recommended phase II dose could not be determined.

This discussion highlights key investigational findings of existing cytotoxic and novel biological therapeutics, combination regimens, and predictive and prognostic biomarkers in the field of gastrointestinal oncology during the past year.

Background: Pelvic radiotherapy with concurrent 5-fluorouracil-based chemotherapy is a component of standard therapy for patients with T3/T4 or node-positive rectal cancer and may be associated with acute gastrointestinal toxicity. In this retrospective study, we sought to compare patient-reported outcomes (PROs) with clinician reports of acute symptoms experienced by rectal cancer patients receiving chemoradiation.

Patients and methods: Charts of 199 patients with rectal cancer who received chemoradiation at some point from November 2006 through February 2011 were reviewed. Clinicians assessed toxicity weekly using Common Terminology for Clinical Adverse Events version 3.0, and, beginning in September 2009, the patients reported symptoms weekly, using the 7-item Bowel Problems Scale. One hundred ninety-seven patients with at least 1 clinician or patient assessment were eligible for the study. We used descriptive statistics to compare patient and clinician assessments in a subgroup of 65 patients (paired group) who had at least 1 patient and clinician assessment on the same day. Cohen's κ coefficient was used to evaluate agreement between the patients and the clinicians.

Results: The patients reported diarrhea and proctitis more often than clinicians reported them throughout treatment. Uncorrected agreement for diarrhea and proctitis was 82% and 72%, respectively. Cohen's κ was .64 for diarrhea, indicating moderate agreement, and .22 for proctitis, indicating only slight agreement.

Conclusions: Our findings suggest a discrepancy between clinician and PRO reports. Further study may discern potential benefits of collecting PROs in prospective studies and in clinical practice.

Background: The pancreatic tumor microenvironment is rich in receptors for platelet-derived growth factor (PDGFRs). Imatinib mesylate (IM) inhibits PDGFRs and decreases tumor interstitial fluid pressure, potentially improving drug access. These data and promising results in a phase 1 trial formed the rationale for a phase 2 trial combining IM and gemcitabine (GEM) in pancreatic cancer.

Methods: Eligibility criteria included chemotherapy-naïve, locally advanced or metastatic pancreatic cancer; ECOG (Eastern Cooperative Oncology Group) performance status ≤2; and adequate end-organ function. The primary end point was progression-free survival (PFS). Secondary end points included response rate, toxicity, and overall survival (OS). GEM was given at 1200 mg/m(2)/120 min on days 3 and 10. IM (400 mg) was taken orally on days 1 to 5 and 8 to 12 of a 21-day cycle. Response was assessed every 3 cycles.

Results: Forty-four patients from 7 centers were enrolled from October 2005 through July 2009. Median age was 62 years. The median number of cycles completed was 3 (range, 0-17). Common adverse effects included neutropenia, nausea, anemia, and fatigue. Half the patients required dose reductions. There were no complete responses to therapy. During treatment, 1 patient showed a partial response, 16 had stable disease, and 18 had progressive disease. The median PFS was 3.9 months (95% confidence interval, 2.1-5.1), the median OS was 6.3 months (95% confidence interval, 5.2-8.5), and the 1-year survival rate was 25.6% (95% confidence interval, 13.8-39.1).

Conclusion: IM in combination with GEM is tolerated in locally advanced, metastatic, or recurrent pancreatic cancer, but does not show a statistically significant PFS or OS benefit over chemotherapy with GEM alone.

Transarterial therapies play an important role in the treatment of hepatocellular carcinoma, both in a palliative setting and as an adjunct to surgery. These therapies exploit the dual blood supply of the liver to selectively target tumors via the hepatic artery, while sparing nontumorous liver. Currently available therapies include transarterial embolization; chemoembolization, with or without drug-eluting beads; and radioembolization. Transarterial techniques are also being used in the development of novel therapies. This article provides an outline of the technical and clinical applications of intraarterial therapies in the treatment of HCC and highlights pertinent future directions.