A phase III study of xilonix in refractory colorectal cancer patients with weight loss.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 685-685 ◽  
Author(s):  
George A. Fisher
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Human Monoclonal Antibody ◽  
Well Being ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Risk Of Death ◽  
Increased Risk ◽  
Median Change

685 Background: Xilonix, an anti-interleukin-1α true human monoclonal antibody is being assessed as cancer therapy to improve overall survival (OS) in advanced colorectal cancer (CRC) patients. Methods: An open label multicenter randomized comparator controlled study to evaluate efficacy and safety of Xilonix in CRC complicated with cachexia. Eligible patients had metastatic CRC, failed oxaliplatin or irinotecan based chemotherapy, and lost ≥5% total body weight in the previous 6 months (m). Patients were 1:1 randomized to Xilonix (3.75 mg/kg intravenously every two weeks) or megestrol acetate (MA, oral 800 mg daily) until progression. Primary endpoint was OS. Secondary endpoints included assessment of patient well-being using the EORTC QLQ-C30 questionnaire. Platelets support tumor growth and metastasis and platelet counts increase during cancer progression. IL-1α on platelets may be a target of Xilonix and thus platelet count was a key pharmacodynamic measure. Results: 40 patients were enrolled between March 2013 and July 2014, at which time the study was halted to revise inclusion criteria to reduce screen failures. An eligibility violation excluded 1 Xilonix patient from analysis (Xilonix n=19, MA n=20). MA treatment arm had a 39% shorter median OS (2.0 versus 2.8 months) and a trend in increased risk of death (hazard ratio 2.17, p=0.17). Physical and role function worsened in patients receiving megesterol (median change of -13.3 (p=0.02), -16.7 (p=0.02) respectively), whereas in Xilonix treated patients these functions did not decline during therapy (median change 0, p=0.88 and 0, p=0.69, respectively). Xilonix patients had treatment-related reduction in platelets compared to the MA group (median -60,000/mm3, vs 10,000/mm3, p=0.03). No infusion reactions, no discontinuations due to adverse events (AEs) and no related SAEs were reported for Xilonix. Conclusions: The trend in OS for Xilonix patients was encouraging and consistent with improved function and intended pharmacodynamic activity. An amended Phase III protocol has been developed to simplify enrollment for an ongoing study of Xilonix in an advanced CRC population. (NCT01767857) Clinical trial information: NCT01767857.

scholarly journals Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer

2012 ◽  
Vol 30 (17) ◽  
pp. 2102-2111 ◽  
Author(s):  
Maura L. Gillison ◽  
Qiang Zhang ◽  
Richard Jordan ◽  
Weihong Xiao ◽  
William H. Westra ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Tobacco Smoking ◽  
Oropharyngeal Cancer ◽  
Radiation Therapy Oncology Group ◽  
Phase Iii ◽  
Tobacco Exposure ◽  
Primary Tumors ◽  
Risk Of Death ◽  
Oropharynx Cancer ◽  
Increased Risk

Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and Methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models. Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026). Conclusion Risk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment.

scholarly journals PRECIOUS: PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke. Rationale and design of a randomised, open, phase III, clinical trial with blinded outcome assessment

2018 ◽  
Vol 3 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Hendrik Reinink ◽  
Jeroen C de Jonge ◽  
Philip M Bath ◽  
Diederik van de Beek ◽  
Eivind Berge ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Acute Stroke ◽  
Outcome Assessment ◽  
Complete Recovery ◽  
Primary Outcome Measure ◽  
Phase Iii ◽  
Open Label ◽  
Risk Of Death ◽  
Increased Risk

Background Elderly patients are at high risk of complications after stroke, such as infections and fever. The occurrence of these complications has been associated with an increased risk of death or dependency. Hypothesis: Prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first four days after stroke onset will improve functional outcome at 90 days in elderly patients with acute stroke. Design International, 3 × 2-factorial, randomised-controlled, open-label clinical trial with blinded outcome assessment (PROBE) in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated to any combination of oral, rectal, or intravenous metoclopramide (10 mg thrice daily); intravenous ceftriaxone (2000 mg once daily); oral, rectal, or intravenous paracetamol (1000 mg four times daily); or usual care, started within 24 h after symptom onset and continued for four days or until complete recovery or discharge from hospital, if earlier. Outcome: The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression. Summary: This trial will provide evidence for a simple, safe and generally available treatment strategy that may reduce the burden of death or disability in patients with stroke at very low costs. Planning: First patient included in May 2016; final follow-up of the last patient by April 2020. Registration: ISRCTN, ISRCTN82217627, https://doi.org/10.1186/ISRCTN82217627

scholarly journals Prediagnostic Plasma Folate and the Risk of Death in Patients With Colorectal Cancer

2008 ◽  
Vol 26 (19) ◽  
pp. 3222-3228 ◽  
Author(s):  
Brian M. Wolpin ◽  
Esther K. Wei ◽  
Kimmie Ng ◽  
Jeffrey A. Meyerhardt ◽  
Jennifer A. Chan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Cox Proportional Hazards ◽  
Folate Intake ◽  
Health Study ◽  
Recent Trial ◽  
Risk Of Death ◽  
Plasma Folate ◽  
Increased Risk ◽  
Overall Mortality

Purpose Although previous studies have demonstrated an inverse relationship between folate intake and colorectal cancer risk, a recent trial suggests that supplemental folic acid may accelerate tumorigenesis among patients with a history of colorectal adenoma. Therefore, high priority has been given to research investigating the influence of folate on cancer progression in patients with colorectal cancer. Patients and Methods To investigate whether prediagnostic levels of plasma folate are associated with colorectal cancer–specific and overall mortality, we performed a prospective, nested observational study within two large US cohorts: the Nurses' Health Study and Health Professionals Follow-Up Study. We measured folate levels among 301 participants who developed colorectal cancer 2 or more years after their plasma was collected and compared participants using Cox proportional hazards models by quintile of plasma folate. Results Higher levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality. Compared with participants in the lowest quintile of plasma folate, those in the highest quintile experienced a multivariable-adjusted hazard ratio for colorectal cancer–specific mortality of 0.42 (95% CI, 0.20 0.88) and overall mortality of 0.46 (95% CI, 0.24 0.88). When the analysis was limited to participants whose plasma was collected within 5 years of cancer diagnosis, no detrimental effect of high plasma folate was noted. In subgroup analyses, no subgroup demonstrated worse survival among participants with higher plasma folate levels. Conclusion In two large prospective cohorts, higher prediagnostic levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality.

A randomized trial of denosumab (AMG 162) versus intravenous (IV) bisphosphonates (BP) in cancer patients (pts) with bone metastases (BM) on established IV BP and evidence of elevated bone resorption

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8562-8562 ◽  
Author(s):  
T. Suarez ◽  
K. Fizazi ◽  
Y. Rahim ◽  
J. Wilson ◽  
M. Fan ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Human Monoclonal Antibody ◽  
Osteoclast Differentiation ◽  
Controlled Study ◽  
Tumor Type ◽  
Open Label ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Skeletal Related Events ◽  
And Function

8562 Background: Pts on established (≥ 8 weeks) IV BP who have elevated bone resorption markers, especially urinary N-telopeptide (uNTx), are at increased risk for skeletal related events (Coleman, J Clin Oncol 2005). Denosumab, a fully human monoclonal antibody, inhibits osteoclastic bone resorption by binding and neutralizing RANK ligand, a key mediator of osteoclast differentiation and function. Denosumab efficacy and safety were evaluated in a phase 2, randomized, open label, active-controlled study in advanced cancer pts with BM and elevated levels of uNTX despite established IV BP therapy. We report preliminary results from an interim analysis of 49 pts at week 13. Methods: Eligible pts (≥18 yrs old with solid tumor [except lung] or multiple myeloma [MM]; confirmed BM; screening uNTx > 50 nM BCE/mM creatinine [Cr]; on IV BP for ≥ 8 weeks before randomization) are stratified by baseline uNTx (50–100, >100) and tumor type. Pts are randomized to 1 of 3 arms: IV BP every 4 weeks (Q4W) or 180 mg denosumab given subcutaneously Q4W or Q12W. The primary endpoint is the proportion (%) of pts with uNTx < 50 nM BCE/mM Cr at week 13. Enrollment is ongoing (planned N = 135). Results: The mean (range) age of all pts in the analysis (33 denosumab; 16 BP) was 62.5 (39, 81) yrs; 96% had > 2 BM. The median time on prior IV BP (mostly zoledronic acid) was 5.1 months. Tumors included prostate (n = 24), breast (n = 20), other/MM (n = 5). The % of pts with uNTx < 50 nM BCE/mM Cr at week 13 was greater with denosumab (pooled arms) than IV BP: 76% (95% CI: 60.3, 91.2) vs 38% (95% CI: 18.5, 61.4; P = .015 Cochran-Mantel-Haenzel), respectively. No treatment-related serious adverse events (SAEs) were reported. Commonly reported AEs in the denosumab arms included nausea, peripheral edema, anemia, bone pain, and constipation. At data cutoff, 10 deaths (6/33 denosumab, 4/16 BP) had occurred on-study. Conclusions: These interim data suggest that denosumab normalizes uNTx more frequently than IV BP in pts with elevated uNTx despite 8 weeks of IV BP, across all tumor types. The AE profile of denosumab appeared similar to that of cancer pts undergoing treatment. [Table: see text]

Impact of Diabetes Mellitus and Insulin Use on Survival After Colorectal Cancer Diagnosis: The Cancer Prevention Study-II Nutrition Cohort

2012 ◽  
Vol 30 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Ahmed N. Dehal ◽  
Christina C. Newton ◽  
Eric J. Jacobs ◽  
Alpa V. Patel ◽  
Susan M. Gapstur ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Cancer Prevention ◽  
Cox Proportional Hazards ◽  
Prevention Study ◽  
Men And Women ◽  
Risk Of Death ◽  
Increased Risk ◽  
Specific Mortality ◽  
Insulin Use

Purpose To examine the association between type 2 diabetes mellitus (T2DM) and survival among patients with colorectal cancer (CRC) and to evaluate whether this association varies by sex, insulin treatment, and durations of T2DM and insulin use. Patients and Methods This study was conducted among 2,278 men and women diagnosed with nonmetastatic colon or rectal cancer between 1992 and 2007 in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of cancer incidence. In 1992 to 1993, participants completed a detailed, self-administrated questionnaire. Vital status and cause of death were ascertained through the end of 2008. Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression. Results Among the 2,278 men and women with nonmetastatic CRC, there were 842 deaths by the end of follow-up (including 377 deaths from CRC and 152 deaths from cardiovascular disease [CVD]). Among men and women combined, compared with patients without T2DM, patients with CRC and T2DM were at higher risk of all-cause mortality (RR, 1.53; 95% CI, 1.28 to 1.83), CRC-specific mortality (RR, 1.29; 95% CI, 0.98 to 1.70), and CVD-specific mortality (RR, 2.16; 95% CI, 1.44 to 3.24), with no apparent differences by sex or durations of T2DM or insulin use. Insulin use, compared with no T2DM, was associated with increased risk of death from all causes (RR, 1.68; 95% CI, 1.22 to 2.31) and CVD (RR, 3.87; 95% CI, 2.12 to 7.08) but not from CRC (RR, 0.58; 95% CI, 0.28 to 1.19). Conclusion Patients with CRC and T2DM have a higher risk of mortality than patients with CRC who do not have T2DM, especially a higher risk of death from CVD.

Symptomatic Treatment With Lanreotide Microparticles in Inoperable Bowel Obstruction Resulting From Peritoneal Carcinomatosis: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

2012 ◽  
Vol 30 (35) ◽  
pp. 4337-4343 ◽  
Author(s):  
Pascale Mariani ◽  
Joëlle Blumberg ◽  
Alain Landau ◽  
Daniela Lebrun-Jezekova ◽  
Estelle Botton ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Bowel Obstruction ◽  
Well Being ◽  
Symptomatic Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Parallel Group ◽  
Intent To Treat

Purpose To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. Patients and Methods In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles (n = 43) or placebo (n = 37) in a 10-day, double-blind, parallel-group phase. The primary end point was the proportion of patients responding on day 7 (one or fewer episodes of vomiting per day or no vomiting recurrence after NGT removal [for ≥ 3 consecutive days in both cases]). Vomiting frequency/NGT secretion volumes, nausea, abdominal pain, well-being, and safety were also assessed. Patients could then enter an open-label lanreotide-only phase. The study was conducted at 22 European hospitals. Results More patients receiving lanreotide than placebo were responders; this difference was not statistically significant for the intent-to-treat (ITT) population on the basis of diary cards (primary analysis; 41.9% [18 of 43] v 29.7% [11 of 37], respectively; odds ratio, 1.75; 95% CI, 0.68 to 4.49; P = .24) but was statistically significant for the corresponding supportive per protocol analysis (57.7% [15 of 26] v 30.4% [seven of 23]; P < .05) and ITT analysis, on the basis of investigators' assessments (50.0% [19 of 38] v 28.6% [10 of 35]; P < .05). Improvements in well-being were significantly greater with lanreotide on days 3, 6, and 7. No significant differences were observed for other secondary end points. Only two (mild/moderate) treatment-emergent adverse events were considered related to lanreotide. Conclusion These results show that lanreotide has some efficacy and is safe in the symptomatic treatment of patients with inoperable bowel obstruction due to peritoneal carcinomatosis.

scholarly journals Colorectal cancer survival among Ministry of National Guard-Health Affairs (MNG-HA) population 2009–2017: retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mesnad Alyabsi ◽  
Fouad Sabatin ◽  
Majed Ramadan ◽  
Abdul Rahman Jazieh
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Cancer Survival ◽  
National Guard ◽  
Population Based ◽  
Risk Of Death ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Cox Proportional Hazard Models

Abstract Background Colorectal cancer (CRC) is the most diagnosed cancer among males and third among females in Saudi Arabia, with up to two-third diagnosed at advanced stage. The objective of our study was to estimate CRC survival and determine prognostic factors. Methods Ministry of National Guard- Health Affairs (MNG-HA) registry data was utilized to identify patients diagnosed with CRC between 2009 and 2017. Cases were followed until December 30th, 2017 to assess their one-, three-, and five-year CRC-specific survivals. Kaplan-Meier method and Cox proportional hazard models were used to assess survival from CRC. Results A total of 1012 CRC patients were diagnosed during 2009–2017. Nearly, one-fourth of the patients presented with rectal tumor, 42.89% with left colon and 33.41% of the cases were diagnosed at distant metastasis stage. The overall one-, three-, and five-year survival were 83, 65 and 52.0%, respectively. The five-year survival was 79.85% for localized stage, 63.25% for regional stage and 20.31% for distant metastasis. Multivariate analyses showed that age, diagnosis period, stage, nationality, basis of diagnosis, morphology and location of tumor were associated with survival. Conclusions Findings reveal poor survival compared to Surveillance, Epidemiology, and End Results (SEER) population. Diagnoses at late stage and no surgical and/or perioperative chemotherapy were associated with increased risk of death. Population-based screening in this population should be considered.

Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report

2021 ◽  
Author(s):  
Patrick J. Leavey ◽  
Nadia N. Laack ◽  
Mark D. Krailo ◽  
Allen Buxton ◽  
R. Lor Randall ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Tumor Volume ◽  
Phase Iii ◽  
Pelvic Bone ◽  
Experimental Therapy ◽  
Survival Outcomes ◽  
Primary Tumors ◽  
Risk Of Death ◽  
Increased Risk ◽  
To Receive

PURPOSE The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.

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