Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial.

BACKGROUND: Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. FINDINGS: Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. INTERPRETATION: In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. FUNDING: Amgen.

Association of Clinical Researchers and Educators a statement on relationships between physicians and industry.

Collaborations between physicians, particularly those in academic medicine, and industries that develop pharmaceutical products, medical devices, and diagnostic tests have led to substantial advances in patient care. At the same time, there is a strong awareness that these relationships, however beneficial they may be, should conform to established principles of ethical professional practice. Through a writing committee drawn from diverse disciplines across several institutions, the Association of Clinical Researchers and Educators (ACRE) has written a code of conduct to provide guidance to physicians in observing these principles. Our recommendations are not intended to be prescriptive or inflexible, but rather to be of assistance to physicians in making their own personal decisions on whether, or how, to be involved in research, education, or other collaborations with industry.

Rituximab: current status as therapy for malignant and benign hematologic disorders.

Rituximab is a chimeric monoclonal antibody targeting the pan-B-cell antigen CD20 and was the first monoclonal antibody approved for clinical use in the treatment of cancer. Since its first approval by the FDA in 1997, investigators have continued to explore a variety of clinical conditions in which rituximab has proven effective with minimal toxicity. Rituximab, as monotherapy or in combination with chemotherapy, has been studied extensively in untreated and relapsed/refractory settings as both induction and maintenance therapy for the treatment of CD20-positive lymphomas and chronic lymphocytic leukemia, in addition to non-malignant hematologic disorders including autoimmune hemolytic anemia and immune thrombocytopenic purpura. Here we discuss the clinical development of rituximab with a review of the efficacy data from clinical trials and its current status in the practice of hematology and oncology.

Irregular echogenic foci representing coagulation necrosis: a useful but perhaps under-recognized EUS echo feature of malignant lymph node invasion.

BACKGROUND AND AIMS: Coagulation necrosis has been described in malignant lymph nodes. Our aim was to determine if coagulation necrosis in mediastinal lymph nodes imaged by EUS could be used as a useful echo feature for predicting malignant invasion. METHODS AND DESIGN: Patients with known or suspected lung cancer who had undergone mediastinal lymph node staging by EUS. SETTING: Tertiary Care university hospital. PARTICIPANTS AND INTERVENTION: An expert endosonographer blinded to the final diagnosis, reviewed the archived digital EUS images of lymph nodes prior to being sampled by FNA. LNs positive for malignancy by FNA were included. The benign group included lymph node images with either negative EUS-FNA or lymph nodes imaged by EUS but not subjected to EUS-FNA, with surgical correlation of their benign nature. RESULTS: 24 patients were included. 8 patients were found to have coagulation necrosis. 7/8 patients had positive result for malignancy by EUS-FNA. One patient determined to have coagulation necrosis had a non-malignant diagnosis indicating a false positive result. 16 patients had no coagulation necrosis. In 6 patients with no coagulation necrosis, the final diagnosis was malignant and in the remaining 10 cases, the final diagnosis was benign. For coagulation necrosis as an echo feature for malignant invasion, sensitivity was 54%, specificity was 91%, positive predictive value was 88%, negative predictive value was 63% and accuracy was 71%. CONCLUSION: Coagulation necrosis is a useful echo feature for mediastinal lymph node staging by EUS.

Knowledge of indications and utilization of EUS: a survey of oncologists in the United States.

BACKGROUND: Since its advent, endoscopic ultrasonography (EUS) has emerged as an invaluable tool in the diagnosis and management of gastrointestinal and adjacent cancers. Yet, it remains unclear how non-gastroenterologists who manage these malignancies use EUS in their practices. METHODS: A link to a self-administered questionnaire, hosted on our university website, was emailed to 650 practicing medical, radiation, and surgical oncologists in the United States. RESULTS: Data were analyzed from 100 responses. When available, the overall utilization of EUS for staging nonsmall cell lung cancer (NSCLC) was significantly low (19.0%), although available. When EUS was unavailable, majority of the patients with pancreatobiliary cancer (79%; P<0.01) were not referred for staging, unlike those with esophageal (57.9%) and rectal cancer (73.7%) were. EUS availability did not impact its use in staging gastric cancer. Majority of the respondents thought EUS made an impact in managing patients with rectal (89.5%), esophageal (84.5%), and pancreatobiliary cancers (58.5%) but not gastric (54.7%) or NSCLC (61.5%). In staging NSCLC, endoscopic ultrasound-guided fine-needle aspirate (35.7%) and mediastinoscopy (34.7%) were noted as the most accurate for tissue sampling of lymph nodes in levels 5, 7, and 8. EUS was deemed better than computerized tomography or magnetic resonance imaging by 42% in detecting small pancreatic tumors. Majority have not referred patients for EUS-guided celiac plexus neurolysis for palliation of pain in unresectable pancreatic cancer. CONCLUSIONS: These data highlight the utilization of EUS that did not necessarily follow established guidelines. Further research is essential to evaluate obstacles to utilization of endoscopic ultrasound-guided fine-needle aspirate.

Temporal trends and predictors of perioperative chemotherapy use in elderly patients with resected nonsmall cell lung cancer.

BACKGROUND: The authors assessed patterns of perioperative chemotherapy use in elderly patients with resected stage I, II, or IIIA nonsmall cell lung cancer (NSCLC) from 1992 to 2002. METHODS: By using data from the Surveillance, Epidemiology, and End Results Program, 11,807 patients were identified who had resected stage I, II, or IIIA NSCLC between 1992 and 2002 and survived >or=120 days beyond diagnosis. The rate of perioperative chemotherapy use was measured by calendar year, and the association between clinical/demographic characteristics and the receipt of chemotherapy was examined by using logistic regression. RESULTS: In total, 957 patients with stage I, II, or IIIA NSCLC (8.1% of the study population) received perioperative chemotherapy. The proportion of patients receiving chemotherapy for stage I NSCLC changed little during the study period. Of 3230 patients with stage II and IIIA NSCLC, 609 patients (18.9%) received chemotherapy, 423 patients (13%) received chemotherapy combined with radiation. 452 patients (15.6%) received adjuvant chemotherapy, and 66 patients (2.3%) received neoadjuvant chemotherapy. The use of chemotherapy increased significantly among patients who were diagnosed after 1994 relative to patients who were diagnosed in 1992 after controlling for sociodemographic and treatment characteristics (P< .001). There was significantly increased use of new-generation chemotherapy agents, such as carboplatin and taxanes (P< .001). The proportion of patients receiving combined-modality therapy also increased significant (P< .001). Younger age, being married, having advanced-stage tumor or adenocarcinoma, having a later diagnosis year, receiving radiation, and seeing an oncologist were predictors for the receipt of chemotherapy (P< .001). CONCLUSIONS: A substantial proportion of Medicare beneficiaries with NSCLC received perioperative chemotherapy. Specifically designed prospective trials that focus on older patients are needed.

Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer.

PURPOSE: We evaluated the efficacy and toxicity of weekly paclitaxel in patients with previously treated advanced urothelial cancer. PATIENTS AND METHODS: Patients with urothelial cancer who had received one prior systemic chemotherapy regimen for advanced disease and had evidence of disease progression were eligible for enrollment. Patients received paclitaxel 80 mg/m(2) by 1-hour intravenous infusion weekly. A cycle of therapy consisted of four weekly treatments. RESULTS: The study enrolled 31 patients. Mean age was 66 years, and 45% of patients had three or more involved metastatic sites. Only 26% of patients had responded to prior chemotherapy. The median number of cycles delivered was three (range, one to eight) at a mean weekly paclitaxel dose of 79 mg/m(2). Three patients achieved a partial response (10%; 95% confidence interval, 0% to 20%). Median time to progression was 2.2 months, and median overall survival time was 7.2 months. Therapy was well tolerated with minimal hematologic toxicity. Grade 3 nonhematologic toxicities were also uncommon. CONCLUSION: Although the overall response rate to weekly paclitaxel in patients with previously treated advanced urothelial cancer was modest, the chemotherapy-refractory nature of the study population should be considered.