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A Randomized Phase II Study of Cetuximab Every 2 Weeks at Either 500 or 750 mg/m2 for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Cancer
Authors: Matthew G. Fury MD, PhDa, Eric Sherman MDa, Donna Lisa BAa, Neeraj Agarwal MDa, Kenneth Algazy MDa, Bruce Brockstein MDa, Corey Langer MDa, Dean Lim MDa, Ranee Mehra MDa, Sandeep K. Rajan MDa, Susan Korte BSa, Brynna Lipson BSa, Furhan Yunus MDa, Tawee Tanvetyanon MDa, Stephanie Smith-Marrone MDa, Kenneth Ng MDa, Han Xiao MDa, Sofia Haque MDa, and David G. Pfister MDa
a From the Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah; University of Pennsylvania Health System, Philadelphia, Pennsylvania; NorthShore University Health System, Chicago, Illinois; Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; City of Hope, Duarte, California; Fox Chase Cancer Center, Philadelphia, Pennsylvania; University of Nebraska Medical Center, Omaha, Nebraska; University of Tennessee Cancer Institute, Memphis, Tennessee; H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida; Memorial Sloan-Kettering Cancer Center, Sleepy Hollow, New York; Memorial Sloan-Kettering Cancer Center, Rockville Center, New York; Memorial Sloan-Kettering Cancer Center, Basking Ridge, New Jersey; and Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Cetuximab is typically administered on a weekly schedule for patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). This study explores cetuximab administered every 2 weeks (q2w). In this multicenter randomized prospective phase II study, eligible patients (≤2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease; ECOG performance status ≤2) were randomized to receive cetuximab q2w at 500 mg/m2 (Group A) or 750 mg/m2 (Group B). The primary end point was response rate (RECIST 1.0). Sixty-one patients were enrolled: 35 in Group A and 26 in Group B, which was closed early for lack of efficacy. Confirmed partial response rates were 11% for Group A (4/35) and 8% for Group B (2/26) according to intention to treat analysis. Partial responses occurred only among patients whose primary tumors were in the oral cavity or larynx. Median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 2.2 and 2.0 months; OS, 7.0 and 9.4 months; Groups A and B, respectively). The most common cetuximab-related adverse events (all grades) among treated subjects included rash, fatigue, and hypomagnesemia. Cetuximab, 500 mg/m2, q2w achieves similar efficacy as conventional dosing for patients with recurrent or metastatic HNSCC. Escalating the dose to 750 mg/m2 q2w offers no obvious therapeutic advantage.
The epidermal growth factor receptor (EGFR) is expressed on virtually all head and neck squamous cell cancer (HNSCC) tumors, and high levels of expression have been associated with unfavorable clinical prognosis.1,2 Cetuximab is a chimeric IgG1 monoclonal antibody that binds to the extracellar domain of EGFR and inhibits ligand binding.3,4 In patients with recurrent or metastatic HNSCC, weekly cetuximab (initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2 intravenously) has been evaluated both as monotherapy and in combination with cytotoxic chemotherapy.5
Cetuximab weekly monotherapy for patients with advanced platinum-refractory HNSCC yielded objective radiographic responses rates of 10% to 13% in phase II studies.6,7 In a randomized phase III study for patients who had not received any prior chemotherapy for recurrent or metastatic HNSCC, subjects received either cetuximab plus cisplatin or placebo plus cisplatin. The objective response rate favored the cetuximab arm (26% vs. 10%; P=.03). However, progression-free survival (PFS) and overall survival (OS) did not differ significantly between the groups.8
The addition of standard weekly cetuximab to platinum-based chemotherapy was evaluated in the EXTREME trial. Subjects (n=442) with recurrent or metastatic HNSCC were randomized to receive cisplatin (or carboplatin, per investigator's choice) plus 5-fluorouracil with or without weekly cetuximab. No prior therapy for recurrent or metastatic disease was allowed. The addition of cetuximab to the platinum plus 5-fluorouracil doublet was associated with significant improvements in response rate (36% vs. 20%), PFS (5.6 vs. 3.3 months), and OS (10.1 vs. 7.4 months).9
The early studies that established weekly dosing of cetuximab did not establish a maximum-tolerated dose,10,11 and subsequent studies explored other doses and schedules of cetuximab. These dose exploration studies were performed in patients with advanced colorectal cancer. One question was whether anti-tumor efficacy could be improved with dose escalation. A second issue was tolerability of every-2-week (q2w) dosing.
In pharmacokinetic studies of q2w dosing of cetuximab in patients with metastatic colorectal cancer, cetuximab doses of 400 to 700 mg/m2 q2w were well tolerated and the maximum tolerated dose was not reached.12 Pharmacokinetic analysis showed that trough levels for the 500 mg/m2 q2w, 600 mg/m2 q2w, and 250 mg/m2 weekly regimens were comparable.12,13 Pharmacodynamic studies, in which subjects underwent skin biopsies at baseline and at week 4 showed that all cetuximab dose levels yielded comparable changes in the expression of phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), Ki67, p27, and phosphorylated signal transducers and activators of transcription 3 (pSTAT3) as detected with immunohistochemistry.14 Based on this work and similar studies,15,16 cetuximab at 500 mg/m2 q2w was identified as a convenient and feasible dose for patients with advanced colorectal cancer.
This study evaluates 2 doses of q2w cetuximab monotherapy, 500 and 750 mg/m2, for patients with recurrent or metastatic HNSCC.
Study Objectives
The primary objective of this study was to evaluate the response rate of 2 separate doses of cetuximab as monotherapy in patients with recurrent or metastatic HNSCC. The secondary objectives of this study were to determine the disease control rate, OS, PFS, safety, and tolerability
Patients aged 18 years or older were eligible if they had histologically or cytologically confirmed HNSCC that was recurrent or metastatic, measurable disease as defined by RECIST,17 ECOG performance status of 2 or less, and adequate hematologic (absolute neutrophil count ≥1200/μL, platelet count ≥100,000/μL), hepatic (total bilirubin ≤1.5 mg/dL and transaminases and alkaline phosphatase ≤5 times the upper limit of normal), and renal function (serum creatinine ≤1.5 times the upper limit of normal or calculated creatinine clearance >40 mL/min). Key exclusion criteria included prior cetuximab therapy in the setting of recurrent or refractory disease, more than 2 prior cytotoxic chemotherapy regimens for metastatic/recurrent disease, uncontrolled central nervous system metastases, or other active invasive malignancies (other than nonmelanoma skin cancers or in situ cervical cancer).
This was a multicenter, open-label, randomized, phase II study for patients with recurrent and/or metastatic HNSCC. The study was approved by the Institutional Review Boards at each of the participating institutions, and all subjects provided written informed consent.
Patients were randomized to receive cetuximab on Group A (500 mg/m2 over 2 hours) or Group B (750 mg/m2 over 3 hours) on day 1 and 15 of each 28-day cycle. Patients continued to receive treatment until disease progression or until other withdrawal criteria were met.
Toxicity Management and Response Assessment
Adverse events were graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Physical examination with assessment of adverse events was required at the start of each 4-week cycle. Toxicity management guidelines included dose delays for grade 3 adverse events (for up to 21 days), and removal from study for any attributable grade 4 toxicity or any hypersensitivity reaction of grade 3 or higher. Patients who maintained active follow-up were followed for at least 30 days after last cetuximab therapy. Radiologic imaging for RECIST assessment17 of indicator lesions was performed every 2 cycles (typically every 8 weeks) and/or after the final study treatment. All reported major responses were reviewed by the Department of Radiology at the lead site, Memorial Sloan-Kettering Cancer Center.
Statistical Considerations
Up to 70 patients total could be randomized to either Group A or Group B (up to 35 patients per group). The response rate for each group was tested against the historical control of 10%.18 A 2-stage Simon optimal design was used in each arm individually to test the null hypothesis that the response rate would be at most 10% versus the alternative that it would be 25% or greater (88.6% power for detection of a 25% response rate in each group). The study had a 12.4% overall type I error. The null hypothesis would be rejected if 6 or more tumor responses occurred among 35 patients in a group.
OS and PFS were analyzed using the Kaplan-Meier method, from which median times were estimated. OS was defined as the time from randomization until death, and PFS was defined as the time from randomization until progression or death. Primary analyses of response rate and survival followed the principle of intention-to-treat (ITT).
The study contained an early stopping rule for lack of efficacy. If 1 or fewer responses were observed after 18 patients per cohort were accrued and evaluated, then the null would be accepted and accrual to the group would be terminated early. Accrual to a given group was allowed to continue without interruption until 18 patients were evaluable in that group. The chance of early stopping under the null hypothesis was 45%, and the chance of early stopping under the alternative (eg, in error) was 4%. Because of the interval between enrollment and response evaluation, accrual beyond 18 subjects in a group was anticipated (and allowed) to occur, until enough patients (n=18) were evaluable for response and/or criteria were met for continued accrual beyond 18 subjects in the group.
Patients who were removed from the study before completing 2 cycles of treatment because of toxicity (or withdrawal of consent, or noncompliance) would not be considered evaluable for the efficacy-based early stopping rule. The early stopping rule for efficacy was based on the first 18 patients in each arm who completed at least 2 cycles of therapy. However, patients removed from the study because of disease progression during cycle 1 or 2 were counted toward the early stopping rule for efficacy.
To optimize patient safety, the protocol also contained an early stopping rule for safety that was independent of the efficacy-based early stopping rule. The early stopping rule for safety held that if 3 or more of the first 18 patients (each group treated separately) experienced a dose-limiting toxicity (as defined in the protocol) during cycle 1 or 2, that group would be closed because of excess toxicity.
The study enrolled 61 patients from 10 cancer centers across the United States. The first subject began treatment on February 8, 2008, and the final subject was registered on November 27, 2009. Thirty-five patients were enrolled in Group A and 26 patients were enrolled in Group B, which was closed early in accordance with the early stopping rule. Patient disposition is summarized in Figure 1. Table 1 summarizes baseline characteristics for all enrolled patients. Median age (59 years in Group A and 61 years in Group B), gender distribution (80% male in Group A and 92% male in Group B), and median performance status (ECOG 1 in Groups A and B) were similar between the groups. Oropharynx was the most common primary tumor site in both groups. Two patients, both in Group B, were enrolled but did not receive any study treatment. These 2 untreated patients are not included in the subsequent safety analyses. The cutoff date for this analysis was May 24, 2011.
Treatment Delivery and Acute Adverse Events
The median number of treatment cycles delivered was 2 for both groups (ranges, <1–13 for Group A; <1–15 for Group B). The most common cetuximab-related adverse events (all grades) among treated subjects included rash, fatigue, and hypomagnesemia. Table 2 presents nonhematologic toxicities that occurred in greater than one-third of patients (regardless of grade) in either group, or which were scored as grade 3 or worse in at least 1 patient and believed to be possibly, probably, or definitely related to cetuximab. The incidence of hypomagnesemia (all grades) was higher in Group B (75%) than in Group A (40%). Of the 11 hypersensitivity reactions, 6 occurred at one site (Moffitt Cancer Center in Florida).
Consolidated Standards of Reporting Trials (CONSORT) diagram.
In Group A, the confirmed partial response rate was 11% (95% CI, 4.5%–26%) according to ITT analysis (4 partial responses among 35 subjects). One additional Group A patient had an unconfirmed partial response. In Group B, the confirmed response rate was 8% (95% CI, 2.1%–24.1%) according to ITT analysis (2 partial responses among 26 subjects). Group B was closed early because of insufficient efficacy according to the stopping rule, because only 1 partial response was observed among the first 18 patients who underwent radiologic response evaluation in Group B.
Table 3 summarizes the best response data for each group. The disease control rate (defined as response plus stable disease rate at the end of cycle 2) was 38% (95% CI, 26.6%–50%) for the entire study population according to ITT analysis. The disease control rate was 46% in Group A (16/35 patients) and 27% in Group B (7/26 patients). No complete responses according to RECIST 1.0 were seen in either group.
The median follow-up for all patients was 24.5 months. Thirty-two deaths occurred in Group A and 20 in Group B. Median OS for patients was 7 months for patients in Group A (range, <1–26+ months; 95% CI for median, 6.1–8.1 months) and 9.4 months for patients in Group B (range, <1–32+ months; 95% CI for median, 3.9–10.6 months). Kaplan-Meier plots for OS are shown in Figure 2.
Median PFS was 2.2 months in Group A (range, <1–9.6 months; 95% CI for median, 1.8–3.7 months) and 2.0 months in Group B (range, <1–14.8 months; 95% CI for median, 1.8–5.3 months). Kaplan-Meier plots for PFS are shown in Figure 3. Survival analyses in Figures 2 and 3 are according to ITT (Group A, n=35; Group B, n=26).
Among the 6 patients with confirmed partial responses, the median duration from randomization until radiologic progression of disease or removal from study was 5.8 months (range, 5.5–13.5 months). Three patients experiencing response had primary tumors of the oral cavity, and 3 had primary tumors of the glottic larynx. Another patient in Group B with a tobacco history of 70 pack-years and base-of-tongue squamous cell cancer that had metastasized to the liver remained on treatment with stable disease (best response, 23% tumor reduction) for 14.6 months. No verified partial responses were observed among 25 patients with oropharynx primaries.
The central finding of this study is that cetuximab at 500 mg/m2 q2w (Group A) is well tolerated as palliative monotherapy for patients with recurrent or metastatic HNSCC, and efficacy (11% confirmed partial response rate) is comparable to that seen with conventional dosing of cetuximab in this patient population. Based on response rate, further escalation of cetuximab dose did not appear likely to increase efficacy for rejection of the null hypothesis. Therefore, Group B (8% confirmed partial response rate) was closed in accordance with the efficacy-based early stopping rule.
In Group A, acneiform rash was the most common toxicity of any grade (66%), and rash was also the most common grade 3 toxicity (11%). These findings are similar to the skin toxicity experiences reported in prior studies of standard weekly or 500 mg/m2 q2w dosing of cetuximab. Among patients with advanced HNSCC receiving standard weekly cetuximab plus 5-fluorouracil in the EXTREME study, the incidence of grade 3 or higher skin reactions was 9%.9 In a retrospective study of biweekly cetuximab among patients (n=88) with advanced colorectal cancer, the incidence of grade skin toxicity was 15%.19
The 6 patients who experienced partial responses in this study all had primary tumor sites in either the oral tongue or glottic larynx. The nonoropharynx primary sites suggest that the tumors were unlikely to be human papillomavirus (HPV)–related,20 although HPV testing of tumors was not required in this protocol. The results suggest a hypothesis that the efficacy of anti-EGFR antibodies against recurrent or metastatic HNSCC may be associated with factors such as primary tumor site and/or HPV status. This hypothesis should be directly tested in a prospective clinical study in which knowledge of tumor HPV status is a required study inclusion criterion.
Patient Baseline Characteristics
Cetuximab-Related Adverse Events
For future studies, either response rate or OS could be appropriate primary end points. OS was at least comparable, if not superior, in Group B. However, the CIs for survival estimates in this study are wide, and Group B was closed early because of low response rate. The experience in this study suggests that further cetuximab dose escalation beyond 500 mg/m2 q2w is unlikely to be associated with clinical benefit in this patient population. Because the study was not powered to evaluate OS as the primary end point, firm conclusions cannot be drawn regarding survival between the groups. Studies centering on survival as a primary end point and evaluating dose escalation to 750 mg/m2 q2w or higher could be justified.
Kaplan-Meier plots for overall survival (OS) in Group A and Group B (orange lines) with 95% CIs (blue and green lines).
This study does not address the combination of cetuximab at 500 mg/m2 q2w with other cytotoxics in HNSCC, although these combinations have been evaluated in other solid tumor types.13,21,22 However, the efficacy and tolerability of cetuximab at 500 mg/m2 q2w in this study for patients with advanced HNSCC, and the pharmacokinetic/pharmacodynamic similarities of q2w and conventional dosing described by others,12,14 suggest that it should be feasible to study this q2w cetuximab regimen in combination with cytotoxic chemotherapy in patients with head and neck cancer. Off-protocol, cetuximab monotherapy at 500 mg/m2 q2w is an appropriate palliative option for some patients with advanced HNSCC (eg, in those for whom exposure to the EXTREME regimen is not believed to be clinically indicated).
Kaplan-Meier plots for progression-free survival (PFS) in Group A and Group B (orange lines) with 95% CIs (blue and green lines).
For patients with recurrent or metastatic HNSCC, cetuximab monotherapy at 500 mg/m2 q2w appears similar to conventional weekly cetuximab in efficacy and tolerability, but further studies are needed to test equivalence directly. Future clinical studies in HNSCC also should seek to explore the combination of q2w cetuximab with radiation therapy and/or other chemotherapy regimens, and to evaluate whether HPV status impacts the efficacy of cetuximab among patients with recurrent or metastatic disease.
The authors wish to thank Dr. Michael Szarek, formerly of Bristol-Myers Squibb, for assistance with the statistical design of the study, and Prabhu Bhagavatheeswaran of Bristol-Myers Squibb for statistical review of the data in the final manuscript.
This study was approved and funded by NCCN from general research support provided by Bristol-Myers Squibb (BMS) Company and ImClone Systems, Incorporated. The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
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Correspondence: Matthew G. Fury, MD, PhD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Department of Medicine, Box 532, New York, NY 10021. E-mail: JNCCN@nccn.org
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text:
Risk, Courage, and Women
Contemporary Voices in Prose and Poetry
Karen A. Waldron (Editor), Janice H. Brazil (Editor), Laura M. Labatt (Editor)
Paperback (8/7/2007)
This unique collection of narratives, essays, and poems includes an original interview with Maya Angelou and pieces by Naomi Shihab Nye, Pat Mora, Rosemary Catacalos, and many others. Each work relates how women have demonstrated courage by taking a risk that has changed their lives.
The Introduction explores courage not as a battlefield quality, but as the result of thoughtful choices demonstrating integrity and self-awareness. Each section opens with a description of its organization and the significance of individual pieces. Themes include sustenance for living, faith in the unknown, the courage of choice, the seams of our lives, and crossing borders. The book begins with a conversation with Dr. Maya Angelou, the embodiment of a courageous woman. She urges readers to "Envision" and concludes the book with the wish "Good morning," inviting all to join her in a new day reflecting "The Power of One." Voices of racial and ethnic diversity speak throughout the work, underscoring both difference and unity in the female experience.
Including role models for university audiences and powerful reflections of life experiences for older readers, this work serves many purposes: a textbook in Literature or Women's/Gender Studies classes, a focus for book study groups, and a source for providing perspective during quiet moments. All net proceeds from book sales will go to the WINGS nonprofit organization, recipient of Oprah's Angel Network award, providing uninsured women with free breast cancer surgery, radiation, counseling, and follow-up treatments such as chemotherapy.
University of North Texas Press, 9781574412338, 384pp.
Karen A. Waldron is Professor Emeritus of Education and former Director of Special Education at Trinity University, San Antonio, Texas. She holds M.S. and Ph.D. degrees from Syracuse University and has supported the education of women and families throughout Europe, the Middle East, Australia, New Zealand, and Hong Kong.
Janice H. Brazil is a widely published poet with involvements in Girl Scouts, Amnesty International, and hospice in Massachusetts, Illinois, and Texas.
Laura M. Labatt has served as president of the Bexar County Women's Center. She focuses her efforts on literacy, career development, and hospice.

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Real Journalism Now
Select Stories, Articles, Reviews, Commentaries and Opinions in These Times of Bad & Fake News, COVID-19 Resurgences, Attacks on Democracy & Other Apocalyptic Menaces
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U.S. Senate Needs to Commence Hearings and Vote on Judge Merrick Garland
by The WORD • July 24, 2016
So says Lawyers' Committee for Civil Rights Under Law.
Edited by Gregg Morris
Lawyers' Committee Releases Report Evaluating Supreme Court Nominee Judge Merrick Garland's Full Record on Civil Rights Cases and Issues Statement to U.S. Senate Urging Immediate Hearing and a Vote
More than 150 Attorneys Across Country Sign Statement Urging Senate to Immediately Commence Hearings Following Passage of 50 Days Since President Identified Court Nominee
WASHINGTON, D.C. – Early in May, the Lawyers' Committee for Civil Rights Under Law released its report evaluating the full civil rights record of Supreme Court nominee Chief Judge Merrick Garland. The report provides an examination of his record on cases concerning voting rights, employment, housing, criminal justice, education and access to justice issues – matters central to the Lawyers' Committee's mission.
As Judge Garland has served on the U.S. Court of Appeals for the District of Columbia Circuit for 18 years, the analysis is based primarily on the opinions he has authored or joined as a judge on that court.
In addition to the report, the Lawyers' Committee also issued a statement joined by more than 150 members of its Board of Directors located across the country to Senate Majority Leader Mitch McConnell, urging the Senate to fulfill its constitutional role and grant Judge Garland fair consideration and a full Senate vote. The statement also expresses concern regarding the current stalemate at the Supreme Court, which impairs the Court's ability to resolve some of the most significant civil rights cases and controversies that routinely come before the Court.
"The Supreme Court occupies a central place in American democracy as the arbiter of some of the most complex and impactful cases that typically arise across our country," said Lawyers' Committee President and Executive Director Kristen Clarke. "However, the ability of the Court to effectively resolve the complex cases that come before it is undermined when elected officials use politics as a reason to prolong the vacancy created in the wake of Justice Scalia's death. We believe that Judge Garland possesses the exceptional competence necessary to serve on the Court and urge the Senate to move forward with hearings to give the public an opportunity to learn more about his commitment to fair interpretation of civil rights laws."
Since its creation in 1963 at the urging of President John F. Kennedy, the Lawyers' Committee has been devoted to the recognition and enforcement of civil rights in the United States. While we have seen significant progress, the challenges of unlawful discrimination remain. Recognizing the Supreme Court's critical role in civil rights enforcement and the central role that the Court plays in our democracy, the Lawyers' Committee has long reviewed the record of nominees to the Court to determine if the nominee demonstrates views that are consistent with the core civil rights principles for which we have long advocated.
In evaluating nominees to the Court, the Lawyers' Committee has employed a rigorous standard with two distinct components: (1) exceptional competence to serve on the Court based on education, experience and engagement in the legal system at the highest levels of responsibility, and (2) profound respect for the importance of protecting the civil rights afforded by the Constitution and the nation's civil rights laws based on a large body of civil rights opinions or comparable information from statements and activities other than service on the bench.
"While Judge Garland does not have an extensive body of opinions in civil rights cases, his decisions have been consistent with core civil rights principles," Clarke added.
Highlights of Judge Garland's Civil Rights Record:
Judge Garland's authored opinions in civil rights cases show him to be fair but moderate and generally careful in going no further than the relevant statutes and precedent warrant.
Most of the civil rights opinions he has authored are in employment cases. He has shown a tendency in those cases to side with discrimination plaintiffs in overcoming motions to dismiss. This suggests his support for the notion that cases alleging actionable discrimination should advance at least to the discovery stage.
In other categories of civil rights cases – housing, voting, education and environmental justice – Judge Garland does not have as many written opinions, but those he has written are consistent with his opinions in employment cases.
He supports claims to the extent they are actionable under the relevant statute and binding precedent. There is no hint in Judge Garland's written opinions of a political agenda or an interest in advancing his personal judicial philosophy. He is guided by the statutory text and clear precedent and, in cases of unsettled questions that require statutory interpretation, the statute's remedial purpose and Congressional intent.
With respect to the criminal justice issues currently in center focus for the Lawyers' Committee – racial disparities in arrest, conviction and sentencing rates, clemency for nonviolent offenders, barriers to reentry, right to counsel, debtors' prisons, etc. – Judge Garland has not written any opinions directly on point. With respect to the scores of opinions he has written in criminal appeals, however, he appears to lean toward an understanding of the cases from the perspective of the prosecutor. In cases involving claims by prisoners, he has shown a willingness to carefully examine the facts of the case and allow the claims to be heard fully and fairly.
About the Lawyers' Committee
The Lawyers' Committee for Civil Rights Under Law (Lawyers' Committee), a nonpartisan, nonprofit organization, was formed in 1963 at the request of President John F. Kennedy to involve the private bar in providing legal services to address racial discrimination. Formed over 50 years ago, we continue our quest of "Moving America Toward Justice." The principal mission of the Lawyers' Committee is to secure, through the rule of law, equal justice under law, particularly in the areas of fair housing and community development; employment; voting; education; environmental justice; and criminal justice. For more information about the Lawyers' Committee, visit www.lawyerscommittee.org.
Gregg Morris can be reached at gmorris@hunter.cuny.edu
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We've gotten a good look at the HTC 10 already thanks to several leaks last week, but a new round of renders give us a look at more color variants HTC is prepping. We have the usual stable of your greys, whites and blacks here, with a nice deviation from the status quo to introduce a muted gold option. One of the white variants also ditches a black front panel to match the rear side.
They look fantastic. But even more interesting is the fact that we learned even more from last week's renders: the April 19th date the device shows isn't just random — @evleaks claims that's the date HTC is scheduled to push the HTC 10 to the masses.
It's not uncommon for device manufacturers to quietly leak the date in this manner, and with April being a fond month for HTC when it comes to flagship launches we have no reason to believe it can't be true. We'll be keeping that date circled on our calendar for sure.


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Neil Patrick Harris plays an extremely devoted gamer in new holiday HBO hit
Ryan Galloway Nov 29, 2021 10:02 pm Nov 29, 2021 10:05 pm
It's the holiday season and there is a ton of film content to check out across all streaming services, whether it vintage hits or potential future classics. HBO Max has just added a Christmas film for the whole family and its currently climbing the service's charts.
8-Bit Christmas, a family comedy starring Neil Patrick Harris is now available to stream. The movie centers on the story of ten-year-old Jake Doyle adventuring to score the newest, best video game system as their Christmas gift: the Nintendo Entertainment System.
The festive film is told from the perspective of a now-adult Jake Doyle, Patrick Harris, as he tells the story to his daughter of how he was able to get the new Nintendo system back in the day by defying all the odds.
The film is set in the 1980s and is packed with ton of nostalgia for other holiday films set in that time. Currently, the film is sitting at number two on HBO Max in the US and other countries. 8-Bit Christmas has also performed well on the critic side of things garnering a 73 percent Rotten Tomatoes Tomatometer and a 74 percent audience score.
If you're after something with holiday spirit that the whole family can enjoy, then check out 8-Bit Christmas. Unfortunately, some regions may not be able to stream the film at this time, but Christmas requires patience.
Right now if you want to catch this new holiday adventure you'll need to check it out on HBO Max.


text:
Do you really want to send LX a message saying you like their work?
(thing) by clockwork Sat Nov 13 1999 at 9:12:34
A record is a recorded sound medium. It's a vinyl disc (usually 7 or 12 inches) with tiny grooves on it that can be played with a turntable. As the needle of the turntable passes through the grooves on the record, the needle vibrates and those vibrations are amplified to recreate the sound pressed on the record. Records were popular from their introduction up through the mid-80's when CDs came out, but have recently come back into fashion with the popularity of DJs.
(idea) by LX Thu May 10 2001 at 17:26:16
In database management, a self-contained entity within a database of one or (usually) several records of mutually similar and/or diverse nature. The record represents a data entry and is (usually) made up of fields. Records can be visualized as rows in a table of one or more columns.
(thing) by fhayashi Tue Jul 24 2001 at 15:18:48
The name of Campagnolo's top-of-the-line bicycle component group.
The Campagnolo Record started out as a cotterless crankset in 1958. The Record group was first introduced in 1960, but it contained many Gran Sport parts. The complete Record gruppo was released in 1968.
Many snobby road bike racers only ride Campy Record-equipped bikes.
The 2001 10-speed gruppo is available forabout $1329.99, by mail order. It contains much titanium and carbon fiber.
(thing) by Noung Mon Dec 17 2001 at 21:10:35
In a database, a record is a set of self-contained data pertaining to one entity in the database. Records are made up of fields, which contain data of a certain type.
Imagine a database of students at a school. Each record would correspond to a student, and be made up of the fields name, address, telephone number, date of birth and a list of subjects the student is studying. You can imagine this as tables of data in a file.
Records may be fixed-length or variable-length. Fixed-length records stay a constant size at all times and therefore can be traversed quickly. For instance, if I know that each record in a database is 200 bytes long, then I can jump straight to record number 4 by jumping 800 bytes into a file. This is called direct access (or random access). Variable-length records allow more flexibility in the size of a file (minimising it, but also allowing it to grow larger if it needs to be done) but means that when accessing the file each record will need to be iterated through on its own, which is slower.
(idea) by ravy Sun Mar 23 2003 at 10:32:33
A police record of one's previous arrests and convictions.
- american underworld dictionary - 1950
(definition) by Webster 1913 Wed Dec 22 1999 at 2:31:09
Re*cord" (r?*k?rd"), v. t. [imp. & p. p. Recorded; p. pr. & vb. n. Recording.] [OE. recorden to repeat, remind, F. recorder, fr. L. recordari to remember; pref. re- re- + cor, cordis, the heart or mind. See Cordial, Heart.]
To recall to mind; to recollect; to remember; to meditate.
[Obs.] "I it you record."
Chaucer.
To repeat; to recite; to sing or play.
They longed to see the day, to hear the lark
Record her hymns, and chant her carols blest.
Fairfax.
To preserve the memory of, by committing to writing, to printing, to inscription, or the like; to make note of; to write or enter in a book or on parchment, for the purpose of preserving authentic evidence of; to register; to enroll; as, to record the proceedings of a court; to record historical events.
Those things that are recorded of him . . . are written in the chronicles of the kings.
1 Esd. i. 42.
To record a deed, mortgage, lease, etc., to have a copy of the same entered in the records of the office designated by law, for the information of the public.
© Webster 1913.
Re*cord", v. i.
To reflect; to ponder.
Praying all the way, and recording upon the words which he before had read.
Fuller.
To sing or repeat a tune.
Whether the birds or she recorded best.
W. Browne.
Rec"ord (r?k"?rd), n. [OF. recort, record, remembrance, attestation, record. See Record, v. t.]
A writing by which same act or event, or a number of acts or events, is recorded; a register; as, a record of the acts of the Hebrew kings; a record of the variations of temperature during a certain time; a family record.
2. Especially:
An official contemporaneous writing by which the acts of some public body, or public officer, are recorded; as, a record of city ordinances; the records of the receiver of taxes.
An authentic official copy of a document which has been entered in a book, or deposited in the keeping of some officer designated by law.
An official contemporaneous memorandum stating the proceedings of a court of justice; a judicial record.
The various legal papers used in a case, together with memoranda of the proceedings of the court; as, it is not permissible to allege facts not in the record.
Testimony; witness; attestation.
John bare record, saying. John i. 32.
That which serves to perpetuate a knowledge of acts or events; a monument; a memorial.
That which has been, or might be, recorded; the known facts in the course, progress, or duration of anything, as in the life of a public man; as, a politician with a good or a bad record.
That which has been publicly achieved in any kind of competitive sport as recorded in some authoritative manner, as the time made by a winning horse in a race.
Court of record (pron. r*krd" in Eng.), a court whose acts and judicial proceedings are written on parchment or in books for a perpetual memorial. -- Debt of record, a debt which appears to be due by the evidence of a court of record, as upon a judgment or a cognizance. -- Trial by record, a trial which is had when a matter of record is pleaded, and the opposite party pleads that there is no such record. In this case the trial is by inspection of the record itself, no other evidence being admissible. Blackstone. -- To beat, ∨ break, the record Sporting, to surpass any performance of like kind as authoritatively recorded; as, to break the record in a walking match.
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Brought down as White, kept down as Black, brought up as None, left with me