Key Center, WA, United States
Key Center, WA, United States

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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.

Twardowski P.W.,City of Hope Comprehensive Cancer Center | Twardowski P.W.,Southwest Oncology Group | Mack P.C.,Southwest Oncology Group | Mack P.C.,University of California at Davis | And 2 more authors.
Clinical Genitourinary Cancer | Year: 2014

Papillary renal cell carcinoma (pRCC) represents the second most common histologic variant of kidney cancer. It exhibits a different molecular signature than clear-cell carcinoma and is typically not associated with mutations in the VHL (von Hippel-Lindau) tumor suppressor gene. pRCC is less responsive to modern drugs introduced in the management of kidney cancer in the past decade. In this article, the heredity and biology of 2 main variants of pRCC are outlined. New targets that are being explored in the treatment of this disease are discussed, with particular emphasis on inhibition of mesenchymal epithelial transition (MET) and epidermal growth factor receptor (EGFR) pathways. We discuss preclinical data providing rationale for the combination of MET and EGFR inhibitors and review recently completed and ongoing clinical trials that attempt to expand our therapeutic options for this important subset of kidney cancer. © 2014 Elsevier Inc.

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.

Schroen A.T.,University of Virginia | Petroni G.R.,University of Virginia | Hongkun Wang,University of Virginia | Gray R.,University of Virginia | And 7 more authors.
Clinical Trials | Year: 2010

Background A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. Purpose We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. Methods A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Results Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (<35% actual/predicted accrual rate) were consistently closed due to insufficient accrual. Limitations This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Conclusion Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining accrual benchmarks for early trial termination or redesign is feasible, but better accrual prediction methods are critically needed. Future studies should focus on identifying trial factors that allow more accurate accrual predictions and strategies that can salvage open trials experiencing slow accrual. © The Author(s), 2010.

Sosman J.A.,Vanderbilt University | Moon J.,Southwest Oncology Group | Tuthill R.J.,Cleveland Clinic | Warneke J.A.,University of Arizona | And 6 more authors.
Cancer | Year: 2011

BACKGROUND: On the basis of retrospective experience at individual centers, it appears that patients with stage IV melanoma who undergo complete resection have a favorable outcome compared with patients with disseminated stage IV disease. The Southwest Oncology Group (SWOG) performed a prospective trial in patients with metastatic melanoma who were enrolled before complete resection of their metastatic disease and provided prospective outcomes in the cooperative group setting. METHODS: Based on their physical examination and radiologic imaging studies, patients with a stage IV melanoma judged amenable to complete resection underwent surgery within 28 days of enrollment. All eligible patients were followed with scans (computed tomography or positron emission tomography) every 6 months until relapse and death. RESULTS: Seventy-seven patients were enrolled from 18 different centers. Of those, 5 patients were ineligible; 2 had stage III disease alone; and 3 had no melanoma in their surgical specimen. In addition, 8 eligible patients had incompletely resected tumor. Therefore, the primary analysis included 64 completely resected patients. Twenty patients (31%) had visceral disease. With a median follow-up of 5 years, the median relapse-free survival was 5 months (95% CI, 3-7 months) whereas median overall survival was 21 months (95% CI, 16-34 months). Overall survivals at 3 and 4 years were 36% and 31%, respectively. CONCLUSIONS: In a prospective multicenter setting, appropriately selected patients with stage IV melanoma achieved prolonged overall survival after complete surgical resection. Although median relapse-free survival was only 5 months, patients could still frequently undergo subsequent surgery for isolated recurrences. This patient population is appropriate for aggressive surgical therapy and for trials evaluating adjuvant therapy. Cancer 2011;. © 2011 American Cancer Society. One of the only prospective analyses of surgery for metastatic disease in patients with stage IV disease, this article reports on a multicenter cooperative group trial with enrollment of patients from 18 different institutions. Incorporating consistent monitoring is a hallmark of cooperative group trials. Copyright © 2011 American Cancer Society.

Von Mehren M.,Chase Medical | Rankin C.,Southwest Oncology Group | Goldblum J.R.,Cleveland Clinic | Demetri G.D.,Dana-Farber Cancer Institute | And 5 more authors.
Cancer | Year: 2012

BACKGROUND: Patients with advanced soft tissue sarcomas (STS) have limited therapeutic options. Sorafenib (BAY 43-9006) is a multitargeted tyrosine kinase inhibitor of raf, vascular endothelial growth factor receptors 1 (VEGFR1) through 3, platelet-derived growth factor B, fms-like tyrosine kinase 3, and c-kit, and some of these may be relevant in STS. METHODS: The authors tested sorafenib at a dose of 400 mg twice daily in patients with advanced vascular sarcoma (VS), high-grade liposarcomas, and leiomyosarcomas who had received 0 or 1 previous regimens for advanced disease. RESULTS: Fifty-one patients were accrued to the study, and 37 were evaluable for toxicity and response. There were no unexpected side effects and no confirmed responses. The median progression-free survival was 3 months, and the median overall survival was 17 months. Six of 8 patients in the VS cohort had prolonged clinical benefit (stable disease or better), resulting in a median progression-free survival of 5 months compared with 2 to 3 months for the patients who had liposarcoma and leiomyosarcomas. CONCLUSIONS: Sorafenib at the dose and schedule studied did not result in any responses in the VS, liposarcoma, or leiomyosarcoma cohort according to Response Evaluation Criteria in Solid Tumors. © 2011 American Cancer Society.

Ludwig H.,Center for Oncology and Hematology | Durie B.G.M.,Southwest Oncology Group | McCarthy P.,Roswell Park Cancer Institute | Palumbo A.,University of Turin | And 23 more authors.
Blood | Year: 2012

Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/eventfree survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established.

Powell B.L.,Cancer and Leukemia Group B | Moser B.,Cancer and Leukemia Group B | Stock W.,Cancer and Leukemia Group B | Gallagher R.E.,Eastern Cooperative Oncology Group | And 10 more authors.
Blood | Year: 2010

Arsenic trioxide (As2O3) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age ≥ 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As2O3 consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine. Ninety percent of patients on each arm achieved remission and were eligible to receive their assigned consolidation therapy. Event-free survival, the primary end point, was significantly better for patients assigned to receive As2O3 consolidation, 80% compared with 63% at 3 years (stratified logrank test, P < .0001). Survival, a secondary end point, was better in the As2O3 arm, 86% compared with 81% at 3 years (P = .059). Disease-free survival, a secondary end point, was significantly better in the As2O3 arm, 90% compared with 70% at 3 years (P < .0001). The addition of As2O3 consolidation to standard induction and consolidation therapy significantly improves event-free and disease-free survival in adults with newly diagnosed APL. This trial was registered at (NCT00003934). © 2010 by The American Society of Hematology.

PubMed | Southwest Oncology Group
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

6513 Background: Although adults with AML containing CBF translocations [t(8;21) or inv(16)/t(16;16)] have a high complete response (CR) rate and improved overall survival (OS) compared to other AML patients (pts), not everyone does well.In order to better understand the spectrum of CBF-associated AML, we analyzed 373 pts with newly diagnosed CBF-related AML treated on SWOG, ECOG or MDA protocols.Pts ranged in age from 16-83 (median 39) with a slight male predominance (56%). Overall, 53% of pts had inv(16) or t(16;16) while 47% had t(8;21); 58% had chromosomal abnormalities in addition to the CBF translocation. Pts with t(8;21) tended to be younger (p=0.03), have lower white counts (p<0.0001) and more often have additional chromosomal abnormalities (p<0.0001). CR was achieved in 86% of pts (95% confidence interval [CI] 82-89%) and the estimated resistant disease (RD) rate was 8% (CI 5-12%). Increasing age was the major factor associated with a decreased CR rate (p=0.0029) and increased incidence of RD (p=0.0014). OS at 10 years was 43% (CI 38-49%), and was significantly lower in older pts (p<0.0001) and those with higher peripheral blast percentage (p=0.0001). Relapse-free survival (RFS) was 40% (CI 34-46%) at 10 years and likewise was associated with age and peripheral blast percent. The treatment results did not differ significantly between pts with t(8:21) versus inv(16) and were not significantly influenced by the presence of additional chromosomal abnormalities.Although pts with CBF-associated AML do relatively well with 43% 10-year OS, considerable improvement is needed, particularly in older patients and those presenting with a higher percent of blasts in their peripheral blood. No significant financial relationships to disclose.

PubMed | Southwest Oncology Group
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

6014 Background: Analyses of 1993-1996 SWOG therapeutic trials showed adequate accrual of African Americans and women, but substantial underrepresentation of older patients (65).(Hutchins NEJM 1999) We updated these analyses and added Hispanic and Asian/Pacific Islander (Asian/PI) race/ethnicity categories to determine if heightened national awareness and Medicare coverage of clinical trial costs impacted these rates.Female, African American, Hispanic American, Asian/PI and older patient (65) incidence rates were computed for 1997-2000, with additional analysis of age from 2001-July 2002. Corresponding population rates were derived from projected 1998 US Census data and 1997-1998 NCI SEER data. SWOG and SEER rates were compared within 15 different disease sites.14,632 patients were accrued from 1997-2000 (and 5,645 from 2001- July 2002). In the analysis by sex, non-gender-specific diseases (and non-military/VA affiliation) were studied (n=8,450). Overall, female SWOG accrual was 41% compared to 44% in SEER. Adequate representation was also found in African Americans (9.3% v 9.5% SEER), Hispanic Americans(4.1% v 3.8% SEER), and Asian/PIs (2.2% v 1.7% SEER). Patients 65 accounted for 31% of enrollments in SWOG trials (37% in 2001-July 2002), compared to 61% in SEER (prior analysis: 25% SWOG v 63% SEER). Rates for the common cancers are shown in the table.There was adequate representation of women, African Americans, Hispanic Americans, and Asian/PIs in SWOG clinical trials. Older patients continue to be substantially underrepresented, but the overall trend is promising. However, rates in common tumors remain significantly below SEER estimates, except for prostate cancer. These results mandate increased national attention to this issue and prospective study of accrual barriers. [Figure: see text] No significant financial relationships to disclose.

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