In 2000, using National Institutes of Health/National Cancer Institute (NIH/NCI) U54 funds, a clinical trials shared resource was established at Nashville General Hospital at Meharry to attract more African Americans to national cancer clinical trials. This Report from the Field describes the model used to achieve this end.
Between 1991 and 1999, 67 patients with acute non-lymphocytic leukemia (ANLL) in complete remission received high dose cytarabine (HiDAC) 3 gm/m2 q12h x 12 doses followed by daunorubicin 45 mg/m2/day x 3 days as consolidation therapy. Five year actuarial event free survival (EFS) was 34% +/- 6%. Age was significantly associated with EFS. EFS was 60% +/- 15% in patients age 20 to 29, 48% +/- 16% in patients age 30 to 39, 23% +/- 10% in patients age 40 to 49, 31% +/- 11% in patients age 50 to 59, and 0% in patients age > or = 60. Contrary to other reports which have used different HiDAC regimens, we found no relationship between cytogenetics and EFS. Cytogenetics were defined as favorable risk: t(8;21), inv (16), and del (16); neutral risk: normal or t(15;17); and unfavorable risk: any abnormality not included in favorable risk or neutral risk. EFS was 29% +/- 17% in patients with favorable cytogenetics, 37% +/- 14% in patients with neutral cytogenetics, and 31% +/- 12% in patients with unfavorable cytogenetics. These differences were not statistically significant. Because of the successful use of allogeneic transplantation at relapse in patients with matched related donors, five year actuarial survival (S) in this series was 40% +/- 6%. Five year actuarial survival was 57% +/- 9% for patients age < or = 44 and 25% +/- 8% for patients age > or = 45. This difference is statistically significant, p < .025. Clinicians should be cautious about making clinical decisions regarding consolidation therapy of ANLL on the basis of the presence or absence of cytogenetic abnormalities as the importance of cytogenetics may depend on the specific therapy which is employed.
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.
tion of intracranial tumours are, however, somewhat become therapists; Dr. Ruttenberg, who runs a day- repetitive.The index is satisfactory.The bibliography care unit inspired by the no longer fashionable confines itself to a short list of more advanced texts.psycho-analytic explanations for childhood autism;The purpose and presentation of the book is Dr. Michael Rutter, of the Maudsley Hospital, didactic, so that it is not primarily addressed to London; members of the Indiana team themselves; research workers or to the practical pathologist and Dr. Grey Walter of the Burden Neurological seeking the finer points of neuropathological diagno-Institute, Bristol.His discovery of the EEG con- sis.It will be of considerable value to medical stu-tingent negative variation (CNV) or 'expectancy dents and to pathologists in training, to whom it can wave', which accompanies the anticipation of having be recommended.to act in response to a sensory cue or of receiving a C. S. TREIP second stimulus following a first, points to a new way of exploring the deficits of perception and
6017 Background: Clinical trials (CT) provide the basis for standards of care. However, the rate of accrual to adult cancer CT is 3% and even lower for minorities. The lack of minority patients on CT results in difficulty ascribing standards to these groups. Proposed obstacles for inadequate accrual for ethnic minority participation are speculated to be socio-economic such as an unwillingness to participate in research and a fear of experimentation. We hypothesized that obstacles to accrual on CT for minority populations are predominantly disease-related and not socio-economic. Methods: An NCI funded CT shared resource was established between a comprehensive cancer center and a public hospital serving ethnic minority and economically disadvantaged patients. Over a 3-year period, all patients were screened to determine eligibility for a cooperative or institutional CT. A dedicated team, including nurses experienced in CT, undertook extensive interaction with all patients to facilitate accrual. Results: 462 patients were screened with 134 (29%) having an identified study available. Screened patients included 238 (56%) African Americans (AA), 165 (39%) Caucasians (C), and 20 (5%) Hispanics (H). 73 subjects, 54% of eligible and 16% of all patients, were accrued to a CT. Ethnicity on CT was: AA = 61%, C = 37%, and H = 2%. These accrual rates far exceed the national norm. Reasons eligible patients did not enter a CT were: medical co-morbidities (25%), not meeting eligibility criteria (21%) and inadequate performance status (10%). Only three patients (5%) indicated they did not wish to participate in research. Conclusion: This experience documents how a dedicated research team can enter ethnic minority and low-income patients onto CT. The largest group of patients not entered was due to a study not being available. All ethnic groups were proportionately accrued to CT. Strategies to improve applicability of CT may require design of studies for patients with co-morbidities or advanced disease. No significant financial relationships to disclose.
Abstract: Metastatic breast cancer is an incurable disease even with high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT). Even though phase III studies have not shown a survival advantage for this group as a whole, it is possible that a small subset of patients may benefit from HDC/ASCT with careful patient selection. A total of 198 patients from three different institutions were treated with HDC/ASCT. After complete staging, patients with central nervous system or bone marrow involvement were excluded. The HDC regimen consisted of: Carboplatin 600 mg/m2 IV infusion over 48 hours, Thiotepa 300 mg/m2 IV infusion over 2 hours, and Cytoxan 60 mg/kg IV infusion given over 2 hours ×3 days. The median age at the time of transplant was 46 (24–62) years and median follow-up was 20 months. Hormone receptor status was known in 148 patients, of whom 84 had estrogen receptor (ER) and/or progestrone receptor (PgR)-positive tumors. Eighty patients had no evidence of disease at the time of HDC/ASCT (CR1). At the completion of HDC and ASCT, complete responses (CR) were seen in an additional 57 patients (CR2). Using Kaplan–Meier analysis, the median relapse-free survival (RFS) for the entire group was 15 months and overall survival (OS) was 27 months. The patients in CR1 had a median RFS and OS of 20.7 and 50.6 months, respectively. This was very similar to the RFS and OS in patients achieving CR2 after HDC/ASCT (p < 0.001; median: 19 and 40 months, respectively). In contrast, the patients with persistent residual disease had an RFS and OS of 7 and 12 months (p < 0.001). These data show that patients achieving a CR after HDC/ASCT have a better relapse-free and OS, when compared to patients with persistent residual disease after HDC/ASCT. This study suggests that a subset of patients with residual metastatic breast cancer after standard chemotherapy can achieve CR with HDC and ASCT which may result in better long-term outcome.
