Showing papers by "Malcolm J. Moore published in 2008"

K-ras mutations and benefit from cetuximab in advanced colorectal cancer.

Abstract: BACKGROUND Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value. METHODS We analyzed tumor samples, obtained from 394 of 572 patients (68.9%) with colo rectal cancer who were randomly assigned to receive cetuximab plus best supportive care or best supportive care alone, to look for activating mutations in exon 2 of the K-ras gene. We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups. RESULTS Of the tumors evaluated for K-ras mutations, 42.3% had at least one mutation in exon 2 of the gene. The effectiveness of cetuximab was significantly associated with K-ras mutation status (P = 0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival, respectively). In patients with wild-type K-ras tumors, treatment with cetuximab as compared with supportive care alone significantly improved overall survival (median, 9.5 vs. 4.8 months; hazard ratio for death, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001) and progression-free survival (median, 3.7 months vs. 1.9 months; hazard ratio for progression or death, 0.40; 95% CI, 0.30 to 0.54; P<0.001). Among patients with mutated K-ras tumors, there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival (hazard ratio, 0.98; P = 0.89) or progression-free survival (hazard ratio, 0.99; P = 0.96). In the group of patients receiving best supportive care alone, the mutation status of the K-ras gene was not significantly associated with overall survival (hazard ratio for death, 1.01; P = 0.97). CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab. The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone. (ClinicalTrials.gov number, NCT00079066.)

Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials

Abstract: Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Federation Francophone de Cancerologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leuc...

A Phase 2 study of perifosine in advanced or metastatic breast cancer

Abstract: First- and second-line chemotherapy with anthracyclines and taxanes in metastatic breast cancer yield a modest improvement in survival with potentially significant toxicity. Subsequent lines of chemotherapy yield response rates of 20–25%, with an unknown impact on survival. Perifosine, an oral alkylphospholipid structurally related to miltefosine, has marked activity against breast cancer cell lines and xenograft models, with broad spectrum cellular effects. To determine the efficacy and toxicity of perifosine in patients with metastatic breast cancer patients after up to 2 lines of prior chemotherapy for advanced disease. 18 patients were enrolled, and 17 treated, using a loading/maintenance dose schedule, (day 1, 300 mg, maintenance 150 mg days 2–21) every 28 days, until disease progression or unacceptable toxicity. Median age of patients was 54 (28–69), 16/17 were female, ECOG performance status was 0/1 in 16 patients. Fifteen received at least 1 prior chemotherapy regimen for metastatic disease (maximum 2). A median of 2 cycles (range 1–13) was administered per patient. Sixteen were evaluable for response: 2 had SD for 4 cycles, 1 SD for 13 cycles, 13 progressed by cycle 2. Grade 3/4 drug-related non-hematologic toxicities include: diarrhea (2), vomiting (2), nausea (2), fatigue (2) and anorexia (1). No grade 3/4 hematologic toxicities were seen. Median time to progression was 8 weeks (7–15 weeks). No objective responses were seen in this group of pretreated metastatic breast cancer patients. Disease stabilization was observed in 19% at 2 months.

Neuroendocrine tumors of the gastrointestinal tract: a decade of experience at the Princess Margaret Hospital.

Abstract: Objectives:Neuroendocrine tumors (NETs) are uncommon malignancies with variable natural history and often indolent biological behavior. Over the past decade, novel treatment approaches have been developed. The purpose of this study was to review the experience at the Princess Margaret Hospital in tr

A randomized, double-blind, placebo (P) controlled, multicenter phase III trial to evaluate the efficacy and safety of adding bevacizumab (B) to erlotinib (E) and gemcitabine (G) in patients (pts) with metastatic pancreatic cancer

Abstract: 4507 Background: The phase II B+G trial showed a 21% response rate (RR) with a median overall survival (OS) of 8.8 months [Kindler, JCO 2005]. In the phase III OS trial of G+E vs. G the hazard rati...

Sorafenib for metastatic renal cancer: the Princess Margaret experience.

Abstract: OBJECTIVE Sorafenib, an oral multikinase inhibitor, prolonged progression-free survival when compared with placebo, as second-line therapy for patients with metastatic renal carcinoma (MRC). Grade 3/4 adverse events were reported in 12% of patients. This study presents sorafenib's efficacy and safety in a less selected cohort of patients enrolled in an expanded access program. METHODS Patients with MRC received sorafenib 400 mg twice daily until disease progression. Tumor response was evaluated by RECIST criteria. Adverse events were graded by NCI common toxicity criteria. RESULTS From November 2005 to August 2006, 58 patients were enrolled. The median progression-free survival was 7.5 months (95% CI: 5.4-11.3), and the best responses among 54 patients were 11 (20%) confirmed partial responses, 15 (28%) stable diseases for > or =6 months; 10 patients (18%) had early progression at 8 weeks. Grade 3/4 adverse events occurred in 37 patients (64%; 95% CI: 50%-76%), the most frequent being skin rash in 17 patients (29%), and hand-foot syndrome in 9 patients (15%). Thirty-six (62%) patients required dose reductions and/or treatment interruptions. CONCLUSIONS Sorafenib is effective in a less selected patient population with MRC but leads to more toxicity than described previously.

Impact of opening an acute palliative care unit on administrative outcomes for a general oncology ward.

Abstract: BACKGROUND. Acute palliative care units (APCUs) are gaining popularity in tertiary care centers. In this study, the authors examined the impact of opening an APCU on administrative outcomes for a general oncology ward (GOW) at a comprehensive cancer center. METHODS. The GOW database was reviewed for 3 periods: June 2000 through May 2002 (before the APCU opened), June 2002 through May 2004 (transitional period, including APCU opening in a temporary location), and June 2004 through May 2006 (after opening of the APCU). Data were extracted on demographics, reasons for admission, admission type, waiting time for admission, length of stay (LOS), overstay (>2 days over expected LOS), death rate, and discharge destination. Linear regression analysis and the Cochran-Armitage test were used for data analysis. RESULTS. There were 5340 admissions: The median patient age was 60 years, and 55% of patients were women. The most common primary cancers were head and neck (22%), gynecologic (21%), gastrointestinal (13%), and lung (12%). There were significant trends on the GOW in decreased admissions for palliative care (12.2%, 9.6%, and 7.9%, respectively, for the 3 periods; P < .0001), fewer inpatient deaths (11.4%, 8.6%, and 6.1%, respectively; P < .0001), and fewer patients with prolonged waits for a bed on a palliative care unit (3.4%, 3%, and 1.7%, respectively; P = .002). Admissions increased for interventions (10.4%, 17.3%, and 22.5%, respectively, for the 3 periods; P < .0001) and for chemotherapy (6.8%, 6.6%, and 9.7%, respectively; P = .001). CONCLUSIONS. After the opening of an APCU at the authors' cancer center, the GOW experienced a decrease in administrative endpoints related to palliative and end-of-life care and an increase in endpoints related to cancer-directed interventions. Prospective studies with clinical endpoints will be required to determine whether this specialization of inpatient care improves quality of life, quality of death, and psychosocial well being. Cancer 2008. © 2008 American Cancer Society.

Neoadjuvant treatment for pancreatic cancer--a review.

Abstract: Pancreatic cancer is associated with a poor prognosis While surgical resection is the only treatment that holds the potential of cure, a minority of patients are surgical candidates Despite surgery, the overall survival rates remain low Neoadjuvant treatment has been investigated both in the setting of resectable disease at diagnosis, or in an attempt to downstage locally advanced disease for resection Single institution studies of neoadjuvant chemoradiation have demonstrated favourable outcomes, compared to similar series of patients treated with surgery with or without adjuvant therapy For unresectable disease, partial or complete responses have been observed which have allowed some patients to subsequently undergo resection The reports of neoadjuvant therapy for pancreatic cancer are heterogeneous with regards to patient population, treatment methods and modalities, making comparisons of different regimens inherently flawed To date, no randomized controlled trials of neoadjuvant therapy have been conducted, however given the positive outcomes of single institutional series of neoadjuvant therapy this approach is worthy of further study

A Case of Small Bowel Obstruction Due to Intraluminal Metastases from Metastatic Renal Cell Cancer

Abstract: A 71-year-old man, with a history of metastatic renal cell cancer (RCC), presented with symptoms of a small bowel obstruction with nausea, vomiting, cramps, and diarrhea. He underwent surgery and was found to have intraluminal metastases from his metastatic RCC. Intraluminal metastases are rare and usually present with obstruction, bleeding, or perforation. The mainstay of treatment remains complete surgical excision, even in the face of widely metastatic disease. Surgery not only palliates symptoms, but may also extend survival because metastatic RCC can be a very indolent and unpredictable disease. Furthermore, these patients can now be treated with a new class of antiangiogenic agents that are showing impressive response rates, which may also translate into improved overall survival.

The relationship between the development of rash and clinical and quality of life outcomes in colorectal cancer patients treated with cetuximab in NCIC CTG CO.17

Abstract: 4130 Background: The National Cancer Institute of Canada Clinical Trials Group CO.17 trial, conducted in collaboration with the Australasian Gastrointestinal Trials Group, demonstrated cetuximab mo...

A prospective economic analysis of cost-effectiveness of cetuximab for metastatic colorectal cancer patients from the NCIC CTG and AGITG CO.17 trial

Abstract: 6528 Background: CO.17 study is the first intergroup (Canadian/Australian) trial, that prospectively collected resource utilization and utility data for cetuximab (N=283) vs. best supportive care a...