scholarly journals Racial Differences in Advanced Colorectal Cancer Outcomes and Pharmacogenetics: A Subgroup Analysis of a Large Randomized Clinical Trial

2009 ◽  
Vol 27 (25) ◽  
pp. 4109-4115 ◽  
Author(s):  
Hanna K. Sanoff ◽  
Daniel J. Sargent ◽  
Erin M. Green ◽  
Howard L. McLeod ◽  
Richard M. Goldberg
Keyword(s):  
Colorectal Cancer ◽  
Racial Differences ◽  
Subgroup Analysis ◽  
Dna Analysis ◽  
Performance Status ◽  
Dose Intensity ◽  
Small Sample ◽  
Black And White ◽  
Response To Chemotherapy ◽  
White Patients

Purpose Racial disparities in colorectal cancer (CRC) survival are documented, but there are few data on comparative response to chemotherapy. A subgroup analysis of a multisite National Cancer Institute–sponsored trial (N9741) was performed comparing outcomes of black and white patients with metastatic CRC receiving uniform treatment. Patients and Methods Adverse events (AEs), response rate (RR), time to progression (TTP), overall survival (OS), and dose-intensity were examined as a function of self-reported race in 1,412 patients treated with irinotecan/fluorouracil, fluorouracil/oxaliplatin, or irinotecan/oxaliplatin. Pharmacogenetic analysis was performed on 486 patients with blood available for germline DNA analysis. Results OS was 1.5 months shorter and TTP was 0.6 months shorter in black than white patients (OS: hazard ratio [HR] = 1.13; 95% CI, 0.90 to 1.42; TTP: HR = 0.91, 95% CI, 0.73 to 1.13); neither difference was statistically significant. RR was significantly higher in whites (41%) than blacks (28%; P = .008). Grade 3 or greater AEs were also higher in whites (48%) than blacks (34%; P = .004). These relationships were maintained in multivariate models adjusting for arm, age, sex, and performance status. There was no difference in dose-intensity of delivered therapy. Significant racial differences in prevalence of pharmacogenetic variants were observed, although small sample size precluded investigating the relationship between treatment, race, and genotype. Conclusion OS and TTP are similar in black and white patients treated per protocol with standardized therapy for metastatic CRC. However, RR and AEs vary considerably by race. The marked racial differences in relevant pharmacogenetics, a potential explanation for differing RR and AEs, are worthy of future study.

Racial differences in long-term outcomes among black and white patients with drug-eluting stents

2019 ◽  
Vol 214 ◽  
pp. 46-53
Author(s):  
Lonnie T. Sullivan ◽  
Hillary Mulder ◽  
Karen Chiswell ◽  
Linda K. Shaw ◽  
Tracy Y. Wang ◽  
...  
Keyword(s):  
Racial Differences ◽  
Drug Eluting Stents ◽  
Long Term Outcomes ◽  
Black And White ◽  
Drug Eluting ◽  
White Patients

scholarly journals Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer Aged at Least 75 Years: A Post-Hoc Subgroup Analysis of Three Phase II Trials

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 578 ◽  
Author(s):  
Gerardo Rosati ◽  
Stefano Cordio ◽  
Giorgio Reggiardo ◽  
Giuseppe Aprile ◽  
Alfredo Butera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Subgroup Analysis ◽  
Performance Status ◽  
Phase Ii Trials ◽  
Younger Patients ◽  
Three Phase ◽  
Post Hoc

Patients older than 75 years of age are usually excluded from metastatic colorectal cancer studies based on a combination chemotherapy containing oxaliplatin. Our group conducted three phase II trials in elderly patients in recent years. A post-hoc subgroup analysis of 67 patients aged at least 75 years was included in this study. Oxaliplatin was combined with capecitabine in two trials and with uracil-tegafur (UFT) plus folinic acid in the third trial. In one study, bevacizumab was also added to chemotherapy. The median age of patients was 77 years, and all had a good performance status (0 to 1). The observed overall response rate was 45%, comparable to younger patients (51%, p = 0.49). The estimated median progression-free survival (PFS) time and overall survival (OS) time were 8.7 and 19.3 months, respectively. These results did not significantly differ from those in younger patients (8.0 months for PFS (p = 0.58) and 19.7 months for OS (p = 0.94), respectively). The most common grade 3–4 adverse events included diarrhea (13%), fatigue (13%), peripheral neuropathy (10%), and neutropenia (7%). Moreover, the toxicity was never statistically different from that in younger patients. The efficacy of oxaliplatin-based combination was maintained in fit elderly patients ≥75 years.

Racial differences in molecular subtypes between black and white patients with endometrial cancer

2017 ◽  
Vol 145 ◽  
pp. 11-12
Author(s):  
E.A. Dubil ◽  
C. Tian ◽  
G. Wang ◽  
N.W. Bateman ◽  
D.A. Levine ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Racial Differences ◽  
Molecular Subtypes ◽  
Black And White ◽  
White Patients

Racial differences in the pattern of hematologic toxicity in the treatment of colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 679-679
Author(s):  
Olalekan O. Oluwole ◽  
William Wu ◽  
Steven N. Wolff ◽  
Kenneth R. Hande
Keyword(s):  
Colorectal Cancer ◽  
Racial Differences ◽  
Statistical Significance ◽  
Dihydropyrimidine Dehydrogenase ◽  
Univariate Analysis ◽  
Small Sample ◽  
Categorical Variables ◽  
Hematological Toxicity ◽  
Hematologic Toxicity ◽  
Grade 3

679 Background: 5-fluorouracil (5-FU), a synthetic fluoropyrimidine, is a critical component of chemotherapy in many cancers. Its metabolites inhibit Thymidylate Synthetase (TS) causing cessation of DNA synthesis and are misincorporated into DNA and RNA causing ineffective DNA repair and faulty mRNA splicing. The rate limiting step in the catabolism of 5-FU is by the Dihydropyrimidine Dehydrogenase enzyme (DPD) which catabolizes over 80% of 5-FU. Patients with near total DPD enzymatic deficiency develop life threatening toxicity after a single administration and those with less severe deficiency will have delayed elimination of 5-FU and slowly accumulate active metabolites leading to toxicities. Methods: We conducted a pilot retrospective cohort study of African American (AA) and Caucasian patients treated for colorectal cancer over a 9 year period, 2000 – 2008, in this IRB approved study. The primary outcome of interest was the rate of development of grade 3 or 4 neutropenia (Absolute Neutrophil Count <1000/uL = grade 3 and <500/uL = grade 4). Descriptive and univariate analysis were done. To test for differences between AA and Caucasians, we computed independent t-test for continuous and Fisher’s exact test for categorical variables. Relative Risk (RR) and p-values were computed. All statistics were done with SPSS v19 software. Results: There were 66 evaluable patients (40 men, 26 women), 40 AA, 24 Caucasians and 2 of other races. Thirty-eight patients (15 Caucasians and 23 AA) received 5-FU containing chemotherapy. The two groups were comparable in baseline characteristics. AA were more likely to develop grade 3-4 hematological toxicity. Nine of 23 AA (39.1%) and one of 15 Caucasians (6.7%) developed grade 3-4 hematological toxicity. RR 8.56, 95% confidence interval 0.95 – 421.06 (p-value of 0.0561) Conclusions: These results suggest that AA were more likely than Caucasians to have severe hematologic toxicity with the use of 5-FU containing chemotherapy. This difference did not meet statistical significance due to small sample size and few numbers of events in the Caucasian arm. A larger prospective study is needed to further evaluate the observed difference.

Hepatic arterial embolization adopting polyvinyl alcohol microspheres preloaded with irinotecan versus systemic chemotherapy for hepatic metastases from colorectal cancer: A phase III clinical research trial of activity and quality of life.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 587-587 ◽  
Author(s):  
Giammaria Fiorentini ◽  
Camillo Aliberti ◽  
Massimo Tilli ◽  
Paolo Coschiera ◽  
Andrea Mambrini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Performance Status ◽  
Hepatic Metastases ◽  
Dose Intensity ◽  
Arterial Embolization ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Radical Resection ◽  
Phase Iii ◽  
Clinical Research Trial

587 Background: Patients with liver metastases (LM) from colorectal cancer (CRC) have a severe prognosis with the 5-year survival of 25% after radical resection; for not operable metastases the survival is poor. Embolization using polyvinil alcohol microspheres loaded with IRI 200 mgr (D) is a feasible procedure. FOLFIRI (CT) is active for the treatment of CRC. We planned this phase III study to assess survival as primary endpoint to increase median survival (MS) by 40% at 2-y (HR=0.72). QoL, responses, progression-free survival (PFS) and safety are secondary endpoints. Methods: Between December 2006 and December 2008, 74 pts were randomized, 37 patients to D and 37 to CT. Two D patients had early progression and two CT patients refused. 70 cycles of D were administered in 35 pts, with a dose intensity (DI) of 99%, and 292 CT cycles were delivered to 35 pts with a DI of 90%. Results: At a median follow up of 30 months ( 18-42) we reported (D vs CT): MS 48% vs 28%, Response Rate 70% vs 20%, Acute Toxicity 70% vs 20%, Late Toxicity 20% vs 80%, QoL improvement 65% vs 25%, Costs for each pt: 7,000 vs 24,000 euro. Conclusions: D increased the 30-Months MS difference of 20% compared to CT. D improved responses, Performance Status and reduced costs. D reported higher immediate toxicity, mainly fever and abdominal pain, than CT. Late toxicity, mainly haematological, diarrhoea, asthenia and alopecia, was more common in CT. We conclude that D compared to CT increases survival and palliative results in patients with LM from CRC.

An observational study of a team management approach for first-line XELOX therapy in patients with advanced/recurrent colorectal cancer: The SMILE study (the study of metastatic colorectal cancer to investigate impact of learning effect).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 554-554
Author(s):  
Michio Nakamura ◽  
HIroshi Matsuoka ◽  
Yoshihisa Shibata ◽  
Yoshinori Munemoto ◽  
Hiroyuki Okuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Observational Study ◽  
Small Sample Size ◽  
Depression Scale ◽  
Dose Intensity ◽  
Small Sample ◽  
Management Approach ◽  
First Line ◽  
Fighting Spirit ◽  
Supportive Interventions

554 Background: Although oral chemotherapies such as XELOX are widely favored for convenience and flexibility, these have several disadvantages such as drug non-compliance and delayed discovery of adverse events. So we designed a multicenter, prospective, observational study to evaluate the efficacy of supportive interventions in first-line XELOX for colorectal cancer (CRC) patients (pts). Methods: CRC pts undergoing first-line XELOX (+Bevacizumab) therapy practicing one or more of supportive interventions as follows: 1) a telephone follow-up (TF), 2) instruction on dosage and administration by a pharmacist, 3) skin care instruction by a nurse, and 4) pts education by a doctor were eligible. The objective was to evaluate the incident rate of grade 2 or worse hand-foot syndrome (HFS), QoL, safety, and efficacy. QoL was assessed at baseline, 2, 4, 5 and 8 cycles after the treatment started, using the Hospital Anxiety and Depression Scale (HADS) and the Mental adjustment to cancer scale (MAC). Results: From April 2011 to September 2012, 80 pts were enrolled from 14 institutes. The characteristics were as follows: male/female: 46/34, age median: 63 (36-75), and supportive intervention 1)/2)/3)/4): 36/68/73/78. The incidence of grade 2 or worse HFS during 6 months were 11.1% (n=4) for those received TF (n=36), and 20.5% (n=9) for those received other intervention except TF (n=44). Relative dose intensity (RDI) was 75.7% (TF+/-: 77.7/74.3%) in oxaliplatin and 77.5% (TF+/-: 80.2/75.3%) in capecitabine, respectively. Although a tendency of the QoL score improvement about anxiety, fighting spirit and helplessness in a TF group was observed during the periods from start of therapy to 4 courses, there were no significant differences compared to other interventions except TF. Conclusions: We confirmed that HFS incidence was mitigated in a TF group. In regard to QoL, although we could not show the statistical differences due to some limitations of this study such as small sample size and non-randomized, it was indicated that TS had the potential to improve several QoL about anxiety, fighting spirit, and helplessness. Clinical trial information: UMIN000007185.

scholarly journals Racial Differences in Pain Treatment and Empathy in a Canadian Sample

2012 ◽  
Vol 17 (6) ◽  
pp. 381-384 ◽  
Author(s):  
Kimberley A Kaseweter ◽  
Brian B Drwecki ◽  
Kenneth M Prkachin
Keyword(s):  
Racial Differences ◽  
Facial Expressions ◽  
Undergraduate Students ◽  
Pain Treatment ◽  
Black And White ◽  
Racial Biases ◽  
Patient Race ◽  
Black Patients ◽  
Treatment Bias ◽  
White Patients

BACKGROUND: Evidence of inadequate pain treatment as a result of patient race has been extensively documented, yet remains poorly understood. Previous research has indicated that nonwhite patients are significantly more likely to be undertreated for pain.OBJECTIVE: To determine whether previous findings of racial biases in pain treatment recommendations and empathy are generalizable to a sample of Canadian observers and, if so, to determine whether empathy biases mediate the pain treatment disparity.METHODS: Fifty Canadian undergraduate students (24 men and 26 women) watched videos of black and white patients exhibiting facial expressions of pain. Participants provided pain treatment decisions and reported their feelings of empathy for each patient.RESULTS: Participants demonstrated both a prowhite treatment bias and a prowhite empathy bias, reporting more empathy for white patients than black patients and prescribing more pain treatment for white patients than black patients. Empathy was found to mediate the effect of race on pain treatment.CONCLUSIONS: The results of the present study closely replicate those from a previous study of American observers, providing evidence that a prowhite bias is not a peculiar feature of the American population. These results also add support to the claim that empathy plays a crucial role in racial pain treatment disparity.

A multinational, randomized, phase III trial of XELIRI (+bevacizumab) versus FOLFIRI (+bevacizumab) as the second-line chemotherapy for metastatic colorectal cancer: Asian XELIRI project (AXEPT).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS780-TPS780 ◽  
Author(s):  
Kei Muro ◽  
Tae Won Kim ◽  
Young Suk Park ◽  
Hiroyuki Uetake ◽  
Tomohiro Nishina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Dose Intensity ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Clinical Trial Information ◽  
Line Chemotherapy

TPS780 Background: Life-prolonging systemic therapy such as chemotherapy (FOLFOX, XELOX, FOLFIRI, 5-FU/LV) with / without molecular targeted agents (bevacizumab, afilibercept, cetuximab, panitumumab) are important treatment for metastatic colorectal cancer (mCRC). On the other hand, it is required to establish an evidence of convenient therapy including oral anticancer agent which is expected lower risk of safety. XELIRI was already examined by various doses in this decade, and result of AIO 0604 was regarded as one of the most appropriate regimen. The BIX phase II study showed the tolerability and promising efficacy of the AIO regimen for Japanese mCRC patients (Hamamoto Y, et al. Oncologist 2014). Methods: Asian XELIRI Project (AXEPT) is an East Asian collaborated, open label, randomized phase III clinical trial designed to demonstrate the non-inferiority of XELIRI (+bevacizumab) to the standard of care FOLFIRI (+bevacizumab) as the second-line chemotherapy in patients with mCRC. The primary endpoint is median overall survival. The secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, relative dose intensity, safety, correlation between UGT1A1 polymorphisms (*28, *6) and safety. Eligible patients were 20 years of age and older, had histologically proven CRC, ECOG performance status 0-2, adequate organ function, progression or difficult to continue after first line regimen. Patients were randomized 1:1 to standard FOLFIRI (+bevacizuamb 5mg/kg day1), repeated every 14 days (Group A) or XELIRI, Irinotecan 200mg/m2 day1, and capecitabine 1600mg/m2 day 1-14 (+bevacizumab 7.5mg/kg day1), repeated every 21 days (Group B). A Total of 464 events were needed to show non-inferiority with a two-sided α of 0·05 and a power of 80%, a target sample size of 600 patients was required. (The 95% CI upper limit of the hazard ratio was pre-specified as less than 1.3.). Enrollment has started in December 2013. As of August 2015, 98 centers in the Japan, South Korea and China are participating in this trial. Clinical trial information: NCT01996306. UMIN000012263. Clinical trial information: NCT01996306.

Validation of the Glasgow Microenvironment Score in patients with colon cancer: A pathology-based prognostic tool.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 206-206
Author(s):  
Peter G Alexander ◽  
Antonia K. Roseweir ◽  
Kathryn AF Pennel ◽  
Hester Catharina Van Wyk ◽  
Arfon GMT Powell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Subgroup Analysis ◽  
Small Sample Size ◽  
Prognostic Score ◽  
Venous Invasion ◽  
Small Sample ◽  
Inflammatory Cell Infiltrate ◽  
Emergency Presentation ◽  
Node Positive Disease

206 Background: The Glasgow Microenvironment Score (GMS), comprised of assessment of the tumour inflammatory cell infiltrate (using Klintrup-Mäkinen (KM) grade) and tumour-associated stroma (TSP), has been reported as a stage-independent prognostic score in patients with colorectal cancer. The present study aims to validate the GMS and examines its prognostic utility in the context of stage and MMR status. Methods: Patients who had undergone resection of stage I-III colon cancer were included ( n= 495). GMS was scored by combining KM and TSP as follows: high KM scores 0; low KM with low TSP scores 1; low KM and high TSP scores 2. Cancer specific (CSS) and overall survival (OS) were primary endpoints. Subgroup analysis was performed to assess the utility of GMS according to TNM, venous invasion and MMR status. Results: There were 30% of patients with GMS 0, 56% with GMS 1 and 14% with GMS 2. Five-year survival for GMS 0, 1 and 2 across the whole cohort were 89%, 74% and 66%, respectively. GMS was associated with age, mode of presentation, TNM, venous invasion and MMR status. On multivariate analysis, GMS was independently associated with CSS (HR 1.35, 95% CI: 1.02-1.79, p= 0.04) and OS (HR 1.23, 95% CI: 1.02-1.48, p= 0.03); this was independent of emergency presentation ( p< 0.01), T-stage ( p= 0.03) and N-stage ( p< 0.001) for CSS. Subgroup analysis found that GMS was able to stratify CSS regardless of node-negative or node-positive disease (both p< 0.01), venous invasion ( p< 0.05), elective presentation ( p< 0.01) and MMR-proficient tumours ( p< 0.001), although it was not able to stratify emergency presentation ( n= 154) or MMR-deficient disease ( n= 102) due to small sample size. Universally, the prognosis for GMS 0 was good, but was poor for GMS 2. The prognosis for GMS 1 varied depending on MMR and nodal status. Conclusions: This study validates the use of the GMS as an independent prognostic pathology-based tool for stratification of colon cancer. It could be readily applied to routine clinical practice and may be used to aid decision making regarding adjuvant treatments in colorectal cancer. It should be further validated in prospective randomised trials.

Bolus Fluorouracil and Leucovorin With Oxaliplatin as First-Line Treatment in Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (10) ◽  
pp. 2545-2550 ◽  
Author(s):  
Alberto Ravaioli ◽  
Maurizio Marangolo ◽  
Enzo Pasquini ◽  
Andrea Rossi ◽  
Dino Amadori ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Performance Status ◽  
Initial Dosage ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Bolus Administration ◽  
First Line ◽  
First Line Therapy ◽  
Duration Of Response

PURPOSE: A phase II trial investigated the activity and toxicity of a bolus administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV) therapy in patients with untreated advanced colorectal cancer. PATIENTS AND METHODS: Forty-five patients in this multicenter, open, nonrandomized study received oxaliplatin 130 mg/m2 on the first day of each course and 5-FU and LV 350 mg/m2 and 20 mg/m2, respectively, as a daily bolus for 5 days, every 21 days, for a maximum of six courses. RESULTS: Partial responses occurred in 18 patients, giving an intent-to-treat response rate of 40.0%. Median time to response was 12.7 weeks; median duration of response was 18.4 weeks. Median progression-free survival was 5.9 months; median survival was 14 months. The independent prognostic factors for improved overall survival were good performance status and negative carcino-embryonic antigen blood level. Incidences of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m2. Reversible neurologic toxicity occurred in 44.4% of patients. CONCLUSION: Bolus administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated advanced colorectal cancer is efficacious and safe. In addition to a more favorable safety profile, the 300 mg/m2 dosage offered improved dose-intensity compared with the initial dosage.

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