Purpose: We tested whether 18 polymorphisms in 16 genes (GSTP1, COX2, IL10, EGFR, EGF, FGFR4, CCDN1, VEGFR2, VEGF, CXCR2, IL8, MMP3, ICAM1, ERCC1, RAD51, and XRCC3) would predict disease-free survival (DFS), overall survival (OS), and toxicity in the INT0144 trial, which was designed to investigate different postoperative regimens of 5-fluorouracil (5-FU)-based chemoradiation (CRT) in locally advanced rectal cancers: Arm 1 consisted of bolus 5-FU followed by 5-FU protracted venous infusion (PVI) with radiotherapy; arm 2 was induction and concomitant PVI 5-FU with radiotherapy and arm 3 was induction and concomitant bolus 5-FU with radiotherapy.
Experimental Design: DNA from 746 stage II/III rectal patients enrolled in the Southwest Oncology Group (SWOG) S9304 phase III trial was analyzed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue.
Background: Recurrence and toxicity occur commonly among patients with rectal cancer who are treated with 5-fluorouracil (5-FU). The authors hypothesized that genetic variation in folate-metabolizing genes could play a role in interindividual variability. The objective of the current study was to evaluate the associations between genetic variants in folate-metabolizing genes and clinical outcomes among patients with rectal cancer treated with 5-FU.
View Article and Find Full Text PDFCancer
October 2014
Background: Targeting a single pathway in pancreatic adenocarcinoma (PC) is unlikely to affect its natural history. We tested the hypothesis that simulataneous targeting of the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor-1 (IGF-1R) pathways would significantly improve progression-free survival (PFS) by abrogating reciprocal signaling that promote drug resistance
Methods: This was a phase Ib/II study testing cixutumumab, combined with erlotinib and gemcitabine (G) in patients with untreated metastatic PC. The control arm was erlotinib plus G.
Purpose: 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.
Methods: Trials were predefined as old versus newer era using initial accrual before or after 1995.
Purpose: Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up.
View Article and Find Full Text PDFIntroduction: The specific aims of the study were to evaluate the 2-year overall survival (OS) and progression-free survival (PFS), toxicity profile, and best objective response rate in patients with locally advanced, clinically unresectable esophageal cancer receiving cetuximab, cisplatin, irinotecan, and thoracic radiotherapy (TRT) within a multi-institutional cooperative-group setting.
Methods: Eligible patients (cT4 M0 or medically unresectable, biopsy proven, and noncervical esophageal cancer) were to receive four 21-day cycles of cetuximab 400 mg/m (day 1, cycle 1), cetuximab 250 mg/m (day 8, 15, cycle 1; then days 1, 8, and 15 for subsequent cycles), cisplatin 30 mg/m (days 1 and 8, all cycles), and irinotecan 65 mg/m (days 1 and 8, all cycles). TRT was administered at 1.
J Clin Oncol
December 2011
Purpose: Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40% with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival.
Patients And Methods: Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m(2) on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m(2)/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.
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.
Methods: We assessed 14,611 patients (1218 black and 13,393 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.
Background: Research on barriers to accrual has typically emphasized factors influencing participation after trial activation.
Purpose: We sought to identify factors influencing trial design and accrual predictions prior to trial activation associated with sufficient accrual.
Methods: A 30-question web-based survey was sent to the study chair and lead statistician for all 248 phase III trials open in 1993-2002 by five Clinical Trials Cooperative Groups.
Neuroendocrine tumors (NETs) arise from a variety of anatomic sites and share the capacity for production of hormones and vasoactive peptides. Because of their perceived rarity, NETs have not historically been a focus of rigorous clinical research. However, the diagnosed incidence of NETs has been increasing, and the estimated prevalence in the United States exceeds 100,000 individuals.
View Article and Find Full Text PDFPurpose: This study was undertaken to examine five possible prognostic factors in patients with recurrent stage II and III colon cancer: time from randomization on an adjuvant therapy clinical trial to tumor recurrence (< 1 year, 1 to 2 years, 2 to 3 years, 3 to 4 years, > 4 years), initial stage (II v III), initial adjuvant treatment (fluorouracil [FU]-based v surgery alone), the era in which the patient entered an adjuvant therapy clinical trial (1978 to 1985, 1986 to 1992, 1993 to 1999), and patient age at recurrence.
Methods: The Adjuvant Colon Cancer End Points (ACCENT) data set was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study.
Results: 5,722 (32.
Background: Some, but not all, studies using registry data have suggested a small but significant long-term survival advantage following a curative surgical resection of gastric cancer at hospitals where the volume of such surgeries is high. However, because such data may be significantly influenced by the impact of postoperative mortality, and may be imbalanced for factors important to survival, the true nature of this relationship remains uncertain.
Methods: We conducted a nested volume-outcome study in a sample of 448 surgical survivors with stage IB through IV (M0) gastric and gastroesophageal junction adenocarcinoma, previously randomized to adjuvant chemoradiation after surgery or surgery alone, to measure the effect of hospital surgical volume, as assessed by Medicare claims data, on overall survival and gastric cancer recurrence.
Purpose: A phase II trial of the oral epidermal growth factor receptor (EGFR) inhibitor erlotinib in patients with gastroesophageal adenocarcinomas stratified according to primary tumor location into two groups: gastroesophageal junction (GEJ)/cardia and distal gastric adenocarcinomas.
Patients And Methods: Patients with a histologically proven diagnosis of adenocarcinoma of the GEJ or stomach (ST) that was unresectable or metastatic; presence of measurable disease; no prior chemotherapy for advanced or metastatic cancer; Zubrod performance status (PS) of 0 to 1; and adequate renal, hepatic, and hematologic function were treated with erlotinib 150 mg/d orally. Patient characteristics were median age, GEJ-63 years, ST-64 years; sex, GEJ-84% male and 16% female, ST-60 male and 40 female; Zubrod PS, GEJ-25 had a PS of 0 and 18 had a PS 1, ST-13 had a PS of 0 and 12 had a PS of 1.
Purpose: Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens.
Patients And Methods: After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT).
Purpose: A traditional end point for colon adjuvant clinical trials is overall survival (OS), with 5 years demonstrating adequate follow-up. A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice.
Methods: Individual patient data were pooled from 18 randomized phase III colon cancer adjuvant clinical trials.
Background: Building on results from Southwest Oncology Group trial 8905, this trial was designed to compare low-dose continuous infusion (LDCI) of 5-fluorouracil (5-FU) versus intermittent high-dose infusion (HDI) of 5-FU in disseminated colorectal cancer (CRC) for evidence of survival advantage based on dose intensity. A companion trial was funded to assess molecular parameters associated with fluoropyrimidine response or resistance and toxicity from these treatments.
Patients And Methods: Eligibility included histologic diagnosis of disseminated CRC, measurable or evaluable disease, no previous therapy for metastatic disease, performance status of 0-2, and adequate renal, hepatic, cardiac, and hematologic function.
Purpose: Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer.
Patients And Methods: After surgery, patients were randomly assigned to CIFU 250 mg/m(2)/d for 56 days every 9 weeks for three cycles or FU 425 mg/m(2) and LV 20 mg/m(2) daily for 5 days every 28 to 35 days for six cycles.
Purpose: The purpose of this phase II multi-institutional study was to define the efficacy and toxicity of infusional 5-FU in combination with PALA and leucovorin in patients with advanced colorectal cancer.
Patients And Methods: Patients were required to have histologically confirmed colorectal cancer with distant metastases. The treatment regimen consisted of 5-FU 2600 mg/m(2) as a 24-hours continuous infusion given once a week, concurrently with leucovorin (LV) at 500 mg/m(2) as a 24-hour continuous infusion.
Purpose: Experimental data, both in vivo and in vitro, suggest that the combination of gemcitabine and cisplatin acts synergistically. Within the Southwest Oncology Group, we designed a Phase II trial to test this chemotherapy combination for patients with esophageal cancer.
Experimental Design: Patients with metastatic or recurrent esophageal cancer were treated with gemcitabine 1000 mg/m(2) on days 1, 8, and 15, and cisplatin 100 mg/m(2) on day 15.