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Jatoi A.,Mayo Medical School | Dakhil S.R.,Wichita Community Clinical | Sloan J.A.,Mayo Medical School | Kugler J.W.,Illinois Oncology Research Association | And 6 more authors.
Supportive Care in Cancer | Year: 2011

Purpose: Previous studies suggest tetracycline and other antibiotics lessen the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This study sought to confirm such findings. Methods: Patients starting an EGFR inhibitor were eligible for this randomized, double-blinded, placebo-controlled study and had to be rash-free. They were then randomly assigned to tetracycline 500 mg orally twice a day for 28 days versus a placebo. Rash development and severity (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events were monitored during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of grade 2 or worse rash between study arms; 32 patients per group provided a 90% probability of detecting a 40% difference in incidence with a type I error rate of 0.05 (two-sided). Results: Sixty-five patients were enrolled, and groups were balanced on baseline characteristics. During the first 4 weeks, healthcare provider-reported data found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%), respectively (p=0.62). Comparable grade 2+ rash rates were observed during weeks 5 through 8 as well as with patient-reported rash data throughout the study period. Quality of life was comparable across study arms, and tetracycline was well tolerated. Conclusion: Although previous studies suggest otherwise, this randomized, double-blinded, placebo-controlled study did not find that tetracycline lessened rash incidence or severity in patients who were taking EGFR inhibitors. © 2010 Springer-Verlag.


Eaton B.R.,Emory University | Pugh S.L.,Data Management | Bradley J.D.,University of Washington | Masters G.,Christiana Care Helen Graham Medical Center | And 9 more authors.
Journal of the National Cancer Institute | Year: 2016

Background: The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non-small cell lung cancer (LA-NSCLC) on a phase III trial. Methods: Patients with LA-NSCLC were randomly assigned to 60 Gy or 74 Gy radiotherapy (RT) with concurrent carboplatin/paclitaxel +/- cetuximab on NRG Oncology RTOG 0617. Participating institutions were categorized as low-volume centers (LVCs) or high-volume centers (HVCs) according to the number of patients accrued (≤3 vs > 3). All statistical tests were two-sided. Results: Range of accrual for LVCs (n = 195) vs HVCs (n = 300) was 1 to 3 vs 4 to 18 patients. Baseline characteristics were similar between the two cohorts. Treatment at a HVC was associated with statistically significantly longer overall survival (OS) and progression-free survival (PFS) compared with treatment at a LVC (median OS = 26.2 vs 19.8 months; HR = 0.70, 95% CI = 0.56 to 0.88, P =. 002; median PFS: 11.4 vs 9.7 months, HR = 0.80, 95% CI = 0.65-0.99, P =. 04). Patients treated at HVCs were more often treated with intensity-modulated RT (54.0% vs 39.5%, P =. 002), had a lower esophageal dose (mean = 26.1 vs 28.0 Gy, P =. 03), and had a lower heart dose (median = V5 Gy 38.2% vs 54.1%, P =. 006; V50 Gy 3.6% vs 7.3%, P <. 001). Grade 5 adverse events (AEs) (5.3% vs 9.2%, P =. 09) and RT termination because of AEs (1.3% vs 4.1%, P =. 07) were less common among patients treated at HVCs. HVC remained independently associated with longer OS (P =. 03) when accounting for other factors. Conclusion: Treatment at institutions with higher clinical trial accrual volume is associated with longer OS among patients with LA-NSCLC participating in a phase III trial. © 2016 The Author 2016. Published by Oxford University Press. All rights reserved.


Bepler G.,Barbara Ann Karmanos Cancer Institute | Zinner R.G.,University of Houston | Moon J.,Statistical Center | Calhoun R.,University of California at Davis | And 8 more authors.
Cancer | Year: 2014

BACKGROUND This cooperative group adjuvant phase 2 trial in patients with completely resected stage I non-small cell lung cancer with tumor diameters measuring ≥ 2 cm was designed to assess the feasibility and preliminary efficacy of assigning patients to therapy or observation using a molecularly based decision algorithm. METHODS At least a lobectomy and sampling of recommended mediastinal lymph node stations, good Zubrod performance status, adequate organ function, and a formalin-fixed and paraffin-embedded tumor specimen were required. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were analyzed using immunofluorescence-based in situ automated quantitative image analysis and categorized as high or low using prespecified cutoff values. Patients with high ERCC1 and RRM1 were assigned to observation and all others to 4 cycles of cisplatin and gemcitabine. Feasibility was defined as treatment assignment within 84 days from surgery in > 85% of patients. Secondary objectives were to estimate the 2-year survival. RESULTS Treatment assignment met the feasibility criteria in 88% of eligible patients (71 of 81 patients). The collective 2-year disease-free and overall survival rates were 80% and 96%, respectively. Protein levels for RRM1 fell within the previously established range, ERCC1 levels were slightly lower than expected, and they were significantly correlated (correlation coefficient, 0.4). The rates of assignment of patients to observation (22%) and chemotherapy (78%) were as expected. CONCLUSIONS Gene expression analysis for treatment assignment is feasible. Survival results are encouraging and require future validation. Real-time performance of quantitative in situ ERCC1 and RRM1 analysis requires further development. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.


PubMed | Wichita Community Clinical Oncology Program, Toledo Community Hospital Oncology Program CCOP, Michigan Cancer Research Consortium, Meritcare Hospital CCOP and 4 more.
Type: Clinical Trial, Phase II | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016

Carboplatin (C) and paclitaxel (P) are standard treatments for carcinoma of unknown primary (CUP). Everolimus, an mTOR inhibitor, exhibits activity in diverse cancer types. We did a phase II trial combining everolimus with CP for CUP. We also evaluated whether a gene expression profiling (GEP) test that predicts tissue of origin (TOO) could identify responsive patients.A tumor biopsy was required for central confirmation of CUP and GEP. Patients with metastatic, untreated CUP received everolimus (30 mg weekly) with P (200 mg/m(2)) and C (area under the curve 6) every 3 weeks. The primary end point was response rate (RR), with 22% needed for success. The GEP test categorized patients into two groups: those having a TOO where CP is versus is not considered standard therapy.Of 45 assessable patients, the RR was 36% (95% confidence interval 22% to 51%), which met criteria for success. Grade 3 toxicities were predominantly hematologic (80%). Adequate tissue for GEP was available in 38 patients and predicted 10 different TOOs. Patients with a TOO where platinum/taxane is a standard (n = 19) tended to have higher RR (53% versus 26%) and significantly longer PFS (6.4 versus 3.5 months) and OS (17.8 versus 8.3 months, P = 0.005), compared with patients (n = 19) with a TOO where platinum/taxane is not standard.Everolimus combined with CP demonstrated promising antitumor activity and an acceptable side-effect profile. A tumor biomarker identifying TOO may be useful to select CUP patients for specific antitumor regimens.NCT00936702.


PubMed | Washington University in St. Louis, The Ottawa Hospital Cancer Center, Michigan Cancer Research Consortium, Ford Motor Company and 13 more.
Type: Clinical Trial, Phase III | Journal: JAMA oncology | Year: 2016

A recent randomized radiation dose-escalation trial in unresectable stage III non-small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy.The primary QOL hypothesis predicted a clinically meaningful decline in quality of life (QOL) via the Functional Assessment of Cancer Therapy (FACT)-Lung Cancer Subscale (LCS) in the high-dose RT arm at 3 months.The RTOG 0617 trial was a randomized phase 3 study (conducted from November 2007 to November 2011) in stage III NSCLC using a 2 2 factorial design and stratified by histology, positron emission tomography staging, performance status, and irradiation technique (3-dimensional conformal RT [3D-CRT] vs intensity-modulated RT [IMRT]). A total of 185 institutions in the United States and Canada took part. Of 424 eligible patients with stage III NSCLC randomized, 360 (85%) consented to QOL evaluation, of whom 313 (88%) completed baseline QOL assessments.Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab.The QOL data were collected prospectively via FACT Trial Outcome Index (FACT-TOI), calculated as the sum of the following measures: Physical Well Being (PWB), Functional Well Being (FWB), and the LCS. Data are presented at baseline and 3 and 12 months via minimal clinically meaningful changes of 2 points or more for PWB, FWB, and LCS or 5 points or more for TOI.Of the 313 patients who completed baseline QOL assessments, 219 patients (70%) completed the 3-month QOL assessments, and 137 of the living patients (57%) completed the 12-month assessment. Patient demographics and baseline QOL scores were comparable between the 74-Gy and 60-Gy arms. Significantly more patients in the 74-Gy arm than in the 60-Gy arm had clinically meaningful decline in FACT-LCS at 3 months (45% vs 30%; P = .02). At 12 months, fewer patients who received IMRT (vs 3D-CRT) had clinically meaningful decline in FACT-LCS (21% vs 46%; P = .003). Baseline FACT-TOI was associated with overall survival in multivariate analysis.Despite few differences in clinician-reported toxic effects between treatment arms, QOL analysis demonstrated a clinically meaningful decline in QOL in the 74-Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival.clinicaltrials.gov Identifier: NCT00533949.


Leal A.D.,Mayo Medical School | Qin R.,Alliance Statistics and Data Center | Atherton P.J.,Alliance Statistics and Data Center | Haluska P.,Mayo Medical School | And 7 more authors.
Cancer | Year: 2014

BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. METHODS In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m 2 glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup. CONCLUSIONS The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN. © 2014 American Cancer Society.


Loprinzi C.L.,Alliance Statistics and Data Center | Qin R.,Alliance Statistics and Data Center | Dakhil S.R.,Wichita Community Clinical Oncology Program | Fehrenbacher L.,Kaiser Permanente | And 6 more authors.
Journal of Clinical Oncology | Year: 2014

Purpose: Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy. Intravenous calcium and magnesium have been extensively used to reduce oxaliplatin-induced neurotoxicity. This trial was designed to definitively test whether calcium/magnesium decreases oxaliplatin-related neurotoxicity. Patients and Methods: In all, 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to intravenous calcium/magnesium before and after oxaliplatin, a placebo before and after, or calcium/magnesium before and placebo after. The primary end point was cumulative neurotoxicity measured by the sensory scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy- Induced Peripheral Neuropathy 20 tool. Results: There were no statistically significant neuropathy differences among the study arms as measured by the primary end point or additional measures of neuropathy, including clinician-determined measurement of the time to grade 2 neuropathy by using the National Cancer Institute Common Terminology Criteria for Adverse Events scale or an oxaliplatin-specific neuropathy scale. In addition, calcium/magnesium did not substantially decrease oxaliplatininduced acute neuropathy. Conclusion: This study does not support using calcium/magnesium to protect against oxaliplatin-induced neurotoxicity. © 2013 by American Society of Clinical Oncology.


News Article | December 22, 2016
Site: www.eurekalert.org

Portland, Oregon, Dec. 21, 2016 - The addition of bortezomib to a standard two-drug regimen for multiple myeloma patients significantly lengthened the time before their cancer returned, and significantly lengthened their lives, according to clinical trial results in The Lancet. Investigators from SWOG, the international cancer clinical trials network funded by the National Cancer Institute (NCI), compared the effectiveness of two drug regimens in newly diagnosed patients undergoing their first round of treatment for multiple myeloma, a type of bone marrow cancer. One regimen used in the study was lenalidomide with dexamethasone, a standard first-line treatment. The other drug regimen also included bortezomib, a second-line drug typically given to myeloma patients whose cancer progresses after initial therapy. SWOG researchers found that the addition of bortezomib made a significant difference for myeloma patients, giving them about another year of remission and another year of life. Patients receiving bortezomib, along with lenalidomide and dexamethasone, in their first six months of treatment had a median remission time of 43 months compared to a median remission of 30 months for patients who received lenalidomide and dexamethasone alone. Researchers also found that patients who received bortezomib lived a median of 75 months, or about six years, after their initial treatment. Patients who received the standard two-drug treatment lived a median of 64 months, or about five years, after initial treatment. "There's a lot of excitement about these research findings and this treatment option, which helps myeloma patients stay healthier longer and gives them more time to spend with people they love," said SWOG study principal investigator Brian G.M. Durie, M.D., a physician at Cedars-Sinai Outpatient Cancer Center in Los Angeles and chairman of the board at the International Myeloma Foundation. "Because the research was so solid, and the findings so strong, we're looking at a potential new standard of care." Results of the SWOG study, S0777, first gained attention in December 2015 at the 57th Annual Meeting of the American Society of Hematology (ASH) held in Orlando, Florida. Myeloma is the second most common blood cancer in the world. According to NCI statistics, in 2016 an estimated 30,330 new cases of myeloma will be diagnosed and 12,650 people will die of the disease in the U.S. In recent years, new drugs have brought new hope, and life expectancy for people diagnosed with multiple myeloma is slowly rising. SWOG researchers enrolled 471 eligible and consented adult patients in S0777 between February 2008 and February 2012 at 139 institutions throughout the National Cancer Trials Network (NCTN), the nation's oldest and largest publicly funded cancer research network. The NCTN includes SWOG, the Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, and NRG Oncology, which all enrolled patients to S0777, as well as the Children's Oncology Group, which focuses on pediatric cancers. S0777 patients ranged in age from 28 to 87, had active myeloma, and had not had a stem-cell transplant or any prior treatment for their disease. Patients were randomized into two groups. One group received the standard two-drug treatment for six cycles over six months. That includes lenalidomide, an immunomodulating therapy marketed as Revlimid by Celegene Corporation. The other group received a three-drug combination that included bortezomib, a proteasome inhibitor marketed as Velcade by Millennium Pharmaceuticals. These patients received the triple combination therapy for eight cycles over six months. Despite the increased remission and longevity, the three-drug combination did have a drawback: Patients who received bortezomib were much more likely to experience sensory neuropathy, or tingling, pain, numbness or weakness in their hands and feet. The NCI provided primary grant funding for S0777 and was the sponsor of the study. Millennium Pharmaceuticals, Inc., The Takeda Oncology Company, and Celgene Corporation provided the study drugs under their respective Cooperative Research and Development Agreements with the NCI. A national team of SWOG researchers led S0777. Along with Durie, they include: Antje Hoering, Ph.D, of Cancer Research And Biostatistics; S. Vincent Rajkumar, M.D., of Mayo Clinic; Muneer H. Abidi, M.D., of Spectrum Health and Michigan State University; Joshua Epstein, DS.c, of University of Arkansas for Medical Sciences; Stephen P. Kahanic, M.D., of Souixland Regional Cancer Center; Mohan C. Thakuri, M.D., of Southeast Clinical Oncology Research Consortium NCORP; Frederic J. Reu, M.D., of Cleveland Clinic; Christopher M. Reynolds, M.D., of Michigan Cancer Research Consortium NCORP; Rachael Sexton, M.S., of Cancer Research And Biostatistics; Robert Z. Orlowski, M.D., Ph.D, of MD Anderson Cancer Center; Bart Barlogie, M.D., Ph.D, of University of Arkansas for Medical Sciences; and Angela Dispenzieri, M.D., of Mayo Clinic. SWOG is a global network of researchers that design and conduct cancer clinical trials, and, as part of the Nation Cancer Institute's National Clinical Trials Network, is a major part of the cancer research infrastructure in the U.S. and the world. The group's goal is to change medical practice so it improves the lives of people with cancer. Founded in 1956, SWOG's 1,300 trials have led to the approval of 14 cancer drugs, changed the standard of cancer care more than 100 times, and saved more than 2 million years of human life. Learn more at swog.org.


Kottschade L.A.,Mayo Medical School | Sloan J.A.,Mayo Medical School | Mazurczak M.A.,Siouxland Hematology Oncology | Johnson D.B.,Wichita Community Clinical Oncology | And 6 more authors.
Supportive Care in Cancer | Year: 2011

Background Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a substantial problem for many cancer patients. Pursuant to promising appearing pilot data, the current study evaluated the use of vitamin E for the prevention of CIPN. Methods A phase III, randomized, double-blind, placebocontrolled study was conducted in patients undergoing therapy with neurotoxic chemotherapy, utilizing twice daily dosing of vitamin E (400 mg)/placebo. The primary endpoint was the incidence of grade 2+ sensory neuropathy (SN) toxicity (CTCAE v 3.0) in each treatment arm, analyzed by chi-square testing. Planned sample size was 100 patients per arm to provide 80% power to detect a difference in incidence of grade 2+ SN toxicity from 25% in the placebo group to 10% in the vitamin E group. Results Two-hundred seven patients were enrolled between December 1, 2006 and December 14, 2007, producing 189 evaluable cases for analysis. Cytotoxic agents included taxanes (109), cisplatin (8), carboplatin (2), oxaliplatin (50), or combination (20). There was no difference in the incidence of grade 2+ SN between the two arms (34%- vitamin E, 29%-placebo; P=0.43). There were no significant differences between treatment arms for time to onset of neuropathy (P=0.58), for chemotherapy dose reductions due to neuropathy (P=0.21), or for secondary endpoints derived from patient-reported neuropathy symptom assessments. The treatment was well tolerated overall. Conclusions Vitamin E did not appear to reduce the incidence of sensory neuropathy in the studied group of patients receiving neurotoxic chemotherapy. © Springer-Verlag 2010.


Pruthi S.,Mayo Medical School | Qin R.,Mayo Medical School | Terstreip S.A.,Meritcare Hospital Community Clinical Oncology Program | Liu H.,Mayo Medical School | And 9 more authors.
Menopause | Year: 2012

OBJECTIVE: Preliminary data suggest that flaxseed, a rich source of dietary lignans, may be a potentially effective treatment of hot flashes. A phase III, randomized, placebo, controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes. METHODS: Postmenopausal women with or without breast cancer were randomly assigned to a flaxseed bar (providing 410 mg of lignans) for 6 weeks versus a placebo bar. Participants completed daily, prospective, hot flash diaries during the baseline week, and then ate one study bar per day for 6 weeks while recording their daily hot flashes. The intraparticipant difference in hot flash activity between baseline and the last treatment week was the primary endpoint. Adverse effects were evaluated through a self-report and the Common Terminology Criteria assessment. RESULTS: A total of 188 women were enrolled in this trial. The mean hot flash score was reduced 4.9 in the flaxseed group and 3.5 in the placebo group (P = 0.29). In both groups, slightly more than a third of the women received a 50% reduction in their hot flash score. Only one adverse effect was significantly different between groups, grade 1 pruritus, which was more common in the placebo group (8% vs 1%). Both groups reported abdominal distension, flatulence, diarrhea, and nausea. Adherence and ability to detect treatment assignment did not differ between groups. CONCLUSIONS: The results of this trial do not support the use of 410 mg of lignans for the reduction of hot flashes. The bars were fairly well tolerated, with both groups reporting gastrointestinal effects, probably due to the fiber content.

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