Rochester, United Kingdom
Rochester, United Kingdom

Time filter

Source Type

Sinicrope F.A.,North Central Cancer Treatment Group | Foster N.R.,North Central Cancer Treatment Group | Yothers G.,National Surgery Adjuvant Breast and Bowel Project | Benson A.,Eastern Cooperative Oncology Group | And 6 more authors.
Cancer | Year: 2013

BACKGROUND: Although obesity is an established risk factor for developing colon cancer, its prognostic impact and relation to patient sex in colon cancer survivors remains unclear. METHODS: The authors examined the prognostic and predictive impact of the body mass index (BMI) in patients with stage II and III colon carcinoma (N = 25,291) within the Adjuvant Colon Cancer Endpoints (ACCENT) database. BMI was measured at enrollment in randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Association of BMI with the time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) were determined using Cox regression models. Statistical tests were 2-sided. RESULTS: During a median follow-up of 7.8 years, obese and underweight patients had significantly poorer survival compared with overweight and normal-weight patients. In a multivariable analysis, the adverse prognostic impact of BMI was observed among men but not among women (Pinteraction =.0129). Men with class 2 and 3 obesity (BMI ≥35.0 kg/m2) had a statistically significant reduction in DFS (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.33; P =.0297) compared with normal-weight patients. Underweight patients had a significantly shorter TTR and reduced DFS (HR, 1.18; 95% CI, 1.09-1.28; P <.0001) that was more significant among men (HR, 1.31; 95% CI, 1.15-1.50; P <.0001) than among women (HR, 1.11; 95% CI, 1.01-1.23; P =.0362; Pinteraction =.0340). BMI was not predictive of a benefit from adjuvant treatment. CONCLUSIONS: Obesity and underweight status were associated independently with inferior outcomes in patients with colon cancer who received treatment in adjuvant chemotherapy trials. © 2013 American Cancer Society.

Shi Q.,North Central Cancer Treatment Group
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens. Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage. Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages. Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients.

Gorlia M.T.,EORTC Headquarters | Wu W.,North Central Cancer Treatment Group | Wang M.,Radiation Therapy Oncology Group | Baumert B.G.,Maastricht University | And 8 more authors.
Neuro-Oncology | Year: 2013

Background. In a previous study, the European Organisation for Research and Treatment of Cancer (EORTC) reported a scoring system to predict survival of patients with low-grade gliomas (LGGs). A major issue in the diagnosis of brain tumors is the lack of agreement among pathologists. New models in patients with LGGs diagnosed by central pathology revieware needed. Methods. Datafrom339EORTCpatients withLGGsdiagnosed by central pathology reviewwere used to develop newprognostic models for progression-free survival (PFS) and overall survival (OS). Data from 450 patients with centrally diagnosed LGGs recruited into 2 large studies conducted by North American cooperative groups were used to validate the models. Results. Both PFS and OS were negatively influenced by the presence of baseline neurological deficits, a shorter time since first symptoms (>30 wk), an astrocytic tumor type, and tumors larger than 5 cm in diameter. Early irradiation improved PFS but not OS. Three risk groups have been identified (low, intermediate, and high) and validated.Conclusions. Wehave developed new prognostic models in a more homogeneous LGG population diagnosed by central pathology review. This population better fits with modern practice, where patients are enrolled in clinical trials based on central or panel pathology review.We could validate the models in a large, external, and independent dataset. The models can divide LGG patients into 3 risk groups and provide reliable individual survival predictions. Inclusion of other clinical and molecular factors might still improve models' predictions. © The Author(s) 2013.

Ansell S.M.,Mayo Medical School | Tang H.,Mayo Medical School | Kurtin P.J.,Mayo Medical School | Koenig P.A.,North Central Cancer Treatment Group | And 8 more authors.
The Lancet Oncology | Year: 2011

Background: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma. Methods: In a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375mg/m2 per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with, number NCT00109967. Findings: 71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively). Interpretation: mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma. Funding: National Institutes of Health and the Predolin Foundation. © 2011 Elsevier Ltd.

Yothers G.,N-of-One | Yothers G.,University of Pittsburgh | Sargent D.J.,Mayo Clinic Cancer Center | Sargent D.J.,North Central Cancer Treatment Group | And 13 more authors.
Journal of the National Cancer Institute | Year: 2011

Conclusion Background Among patients with resected colon cancer, black patients have worse survival than whites. We investigated whether disparities in survival and related endpoints would persist when patients were treated with identical therapies in controlled clinical trials.Conclusion Methods We assessed 14611 patients (1218 black and 13393 white) who received standardized adjuvant treatment in 12 randomized controlled clinical trials conducted in North America for resected stage II and stage III colon cancer between 1977 and 2002. Individual patient data on covariates and outcomes were extracted from the Adjuvant Colon Cancer ENdpoinTs (ACCENT) database. The endpoints examined in this meta-analysis were overall survival (time to death), recurrence-free survival (time to recurrence or death), and recurrence-free interval (time to recurrence). Cox models were stratified by study and controlled for sex, stage, age, and treatment to determine the effect of race. Kaplan-Meier estimates were adjusted for similar covariates to control for confounding. All statistical tests were two-sided.Conclusion Results Black patients were younger than whites (median age, 58 vs 61 years, respectively; P <. 001) and more likely to be female (55% vs 45%, respectively; P <. 001). Overall survival was worse in black patients than whites (hazard ratio [HR] of death = 1.22, 95% confidence interval [CI] = 1.11 to 1.34, P <. 001). Five-year overall survival rates for blacks and whites were 68.2% and 72.8%, respectively. When subsets defined by sex, stage, and age were analyzed, overall survival was consistently worse in black patients. Recurrence-free survival was worse in black patients than whites (HR of recurrence or death = 1.14, 95% CI = 1.04 to 1.24, P =. 0045). Three-year recurrence-free survival rates in blacks and whites were 68.4% and 72.1%, respectively. In contrast, recurrence-free interval was similar in black and white patients (HR of recurrence = 1.08, 95% CI = 0.97 to 1.19, P =. 15). Three-year recurrence-free interval rates in blacks and whites were 71.3% and 74.2%, respectively.Conclusion Conclusion sBlack patients with resected stage II and stage III colon cancer who were treated with the same therapy as white patients experienced worse overall and recurrence-free survival, but similar recurrence-free interval, compared with white patients. The differences in survival may be mostly because of factors unrelated to the patients' adjuvant colon cancer treatment. © The Author 2011. Published by Oxford University Press.

Ansell S.M.,Mayo Medical School | Tang H.,Mayo Medical School | Kurtin P.J.,Mayo Medical School | Koenig P.A.,North Central Cancer Treatment Group | And 9 more authors.
Leukemia | Year: 2012

Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4CD25 regulatory T (T reg) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25 T reg cells while rituximab would deplete malignant B cells. Patients received rituximab 375 mg/m 2 weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% confidence interval (CI): 27-69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37-82%). Thirteen patients (57%) experienced grade 3 adverse events and one patient (4%) died. In correlative studies, soluble CD25 and the number of CD25 T cells decreased after treatment; however, there was a compensatory increase in IL-15 and IP-10. We conclude that although the addition of denileukin diftitox to rituximab decreased the number of CD25 T cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression. © 2012 Macmillan Publishers Limited All rights reserved.

Swain S.M.,The Surgical Center | Swain S.M.,Washington Hospital Center | Jeong J.-H.,University of Pittsburgh | Geyer Jr. C.E.,The Surgical Center | And 27 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known. METHODS: We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin- docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women. Results: At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P = 0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P = 0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P = 0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P = 0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status. CONCLUSIONS: Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status. ( number, NCT00003782.). Copyright © 2010 Massachusetts Medical Society.

PubMed | North Central Cancer Treatment Group
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

15553 Background: Synergistic cytotoxicity with combinations of OX and 5-FU have been observed in a number of tumor systems. Both drugs have known radiosensitizing properties. This phase II study was conducted to evaluate the efficacy of concomitant 5-FU, OX and RT followed by GEM in patients (pts) with unresectable pancreatic cancer.Pts with unresectable non-metastatic invasive ductal pancreatic cancer with ECOG performance status of 0-1 were eligible. Surgical staging was not required. Pts received continuous infusion 5-FU 180 mg/m53 eligible pts were enrolled in 14 mos. M:F- 30:23 with a median age of 65 (range: 31- 80). Median follow-up is 21.6 months (range: 14.3 - 29.7), with 9 pts still alive. The confirmed response rate is 6% (3 PR, 0 CR). Median TTP 7.1 mos (95% CI: 4.9-9.0), 12-month survival 34% (95% CI: 20-63%) and median survival 9.3 mos (95% CI: 5.9-11.4) were observed. Fifty (94%) and 10 (19%) pts experienced at least one grade 3+ or grade 4+ AE, respectively, with 1 pt (2%) death due to a cardiovascular event possibly related to protocol therapy. Frequently occurring maximum grade 3/4 AEs (regardless of attribution) are shown in the Table below: Conclusions: These results do not suggest an efficacy benefit for this combined modality therapy regimen. Toxicity results are similar to those seen with other regimens. Future studies will focus on the addition of novel agents in addition to RT in this setting. [Table: see text] [Table: see text].

PubMed | North Central Cancer Treatment Group
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

1513 Background: EGFR inhibitors may potentiate the therapeutic efficacy of RT in GBM patients. To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib plus RT in patients with GBM, we performed the following phase I trial.Patients were stratified based upon the use of enzyme-inducing anticonvulsants (EIACs). Patients with resected or biopsied GBM were treated with erlotinib for a week prior to concurrent erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until progression. The erlotinib dose was escalated in cohorts of 3 with a starting dose of 100mg/day. Intrapatient dose escalation was not allowed. Response was evaluated by MRI and clinical assessment of neurological status every two months.20 patients were enrolled; 19 are evaluable. There were 14 males/5 females, median age 54 years; 7 had undergone biopsy only/ 5 subtotal resections/ 7 gross total resections. Current dose level is 150mg/day erlotinib for patients not on EIACs (group 1) and 200mg/day for patients on EIACs (group 2). MTD has not been reached. DLTs associated with treatment have occurred in Group 1 at 100mg (1 pt with stomatitis, n=7) and at 150mg (no DLTs, n=4). No DLTs have occurred in Group 2 at 100mg (n=3), 150mg (n=3) and 200mg (n=3) but dose was reduced to 150mg in 2 of 3 patients due to a bothersome rash. With a median follow-up of 189 days, there were 8 deaths and 13 progressions. Median time to progression was 161 days (95%CI: 109 to 216) and median survival was 386 days (95% CI: 278 to NR). Best objective response was known and evaluable in 13 patients: 9 had stable disease, 1 had no evidence of disease and 3 had early progression.Toxicity is acceptable at the current doses of erlotinib plus RT. Accrual continues on both arms with the addition of concurrent and adjuvant temozolomide in conjunction with erlotinib and RT. No significant financial relationships to disclose.

PubMed | North Central Cancer Treatment Group
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

22119 Background: The Epidermal Growth Factor Receptor (EGFR, ErbB-1) is a cellular transmembrane receptor that regulates cell growth and survival, and is a therapeutic target. We determined whether EGFR activation, as indicated by EGFR phosphorylation (p-EGFR), is a more clinically important prognostic marker than is EGFR expression.Archival TNM stage II and III primary colon carcinomas (n=303) from patients treated in 5-fluorouracil-based adjuvant therapy trials conducted by the Mayo Clinic/North Central Cancer Treatment Group were studied. Immunohistochemical analysis of p-EGFR (Tyr-1173) and EGFR (Dako phramDx kit) were performed using tissue microarrays. Staining for Ki-67 and caspase-3 proteins was also performed. Protein expression was correlated with clinicopathological variables and patient survival rates.Membranous EGFR was detected in 214 (70.6%) colon cancers and of these, p-EGFR expression was found in 44 of 139 (31.7%) tumors examined. Increased p-EGFR and EGFR intensity were associated with higher proliferation as indicted by a higher median number of Ki-67-positive tumor cells (p= 0.0058 and p< 0.001, respectively). p-EGFR correlated with proximal tumor site (p=0.0331), but not with other clinicopathological variables. Increased EGFR intensity was correlated with apoptosis, analyzed by caspase-3 (p=0.02), and with poor tumor differentiation (p=0.02). In a univariate analysis, tumor stage and number of involved lymph nodes were significantly associated with disease-free and overall survival (OS). Histologic grade was also associated with OS. Neither p-EGFR nor EGFR expression was prognostic by univariate or multivariate analysis.Activated EGFR (p-EGFR) was detected in nearly one-third of primary colon cancers and was associated with increased tumor cell proliferation. However, neither p- EGFR nor EGFR confered prognostic information. No significant financial relationships to disclose.

Loading North Central Cancer Treatment Group collaborators
Loading North Central Cancer Treatment Group collaborators