tbuckley/cabot-search huggingface dataset:
Etoposide and mitoxantrone in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy with cytarabine and idarubicin
Authors: W. M. McHayleh, R. Redner, R. Sehgal, A. Raptis, M. Agha, J. Natale, T. Luong, J. J. Schlesselman, K. Foon, M. Boyiadzis
Journal: Journal of Clinical Oncology (2009)

7073 Background: The goal of induction chemotherapy in acute myeloid leukemia (AML) is complete remission with restoration of normal bone marrow. If residual leukemia is present after the first course of induction therapy, patients receive a second course identical to the first or receive a non-cross resistant antileukemic regimen. Methods: In a retrospective study of adult patients with newly-diagnosed AML treated at the University of Pittsburgh Cancer Institute between December 2002 and May 2008, we evaluated the efficacy and toxicity of mitoxantrone (10 mg/m 2 /d) and etoposide (100 mg/m 2 /d), both administered intravenously within 5 days as second course therapy of patients not responding to first-course induction therapy with cytarabine and idarubicin. Univariate and multivariate associations between patient characteristics and complete response (CR) were assessed by logistic regression, with overall- and relapse-free survival estimated by Kaplan-Meier analysis. Results: 74 AML patients (mean age 56 years, range: 18–73 years) completed treatment with etoposide and mitoxantrone; 29 (39%) achieved CR. Lower CR rate was associated with unfavorable cytogenetic risk status at diagnosis and higher percent blasts prior to treatment with mitoxantrone and etoposide. Ten (14%) patients died due to infectious complications. No grade 3 or 4 hepatic toxicities were observed. One patient developed grade 3 cardiac toxicity. Median duration of neutrophil recovery following therapy in patients achieving CR was 29 days. Median overall survival was 9.0 months (95% CI 5.8–14.9 months). The 29 patients who achieved CR received postremission therapy: 16 of these eventually relapsed, while 4 others died without evidence of relapse. Median duration of relapse-free survival in these 29 patients was 11.0 months (95% CI: 9.0–19.3 months). Conclusions: Our study suggests that the combination of etoposide and mitoxantorne is an active and well-tolerated regimen as second-course therapy in newly diagnosed AML patients who have persistent leukemia after a first course of induction therapy with cytarabine and idarubicin. No significant financial relationships to disclose.
Prognostic significance of primary extranodal diffuse large B-cell lymphoma (DLBCL) in patients treated with R-CHOP
Authors: B. R. Proctor, D. Hui, J. Donaldson, K. J. Savage, T. N. Shenkier, P. J. Hoskins, R. Klasa, G. Randy, C. Joseph, L. H. Sehn
Journal: Journal of Clinical Oncology (2008)

8583 Background: Previous studies in the pre-rituximab era have identified important clinical differences between nodal and primary extranodal DLBCL. We have examined the prognostic significance of primary extranodal DLBCL in the post-rituximab era. Methods: Using the Lymphoid Cancer Database of the British Columbia Cancer Agency, all patients ≥18 years of age diagnosed with DLBCL between January 1999 and May 2006 and treated with an R-CHOP regimen were included for analysis. Patients were excluded if they were HIV positive, presented with disease in the testicular or central nervous system, or had known coincident indolent lymphoma. Primary extranodal DLBCL was defined as disease confined to one or more localized extranodal sites, with no or minimal nearby nodal involvement. Results: 513 patients were identified with the following characteristics: median age 62 y (range 19–93), male 59.1%, stage III/IV 53.8%, elevated LDH 49.5%, and performance status ≥2 38.2%. While 350 (68.2%) had at least some degree of extranodal involvement, only 133 (25.9%) had primary extranodal DLBCL. Among patients with primary extranodal disease, 70 (52.6%), 37 (27.8%) and 26 (19.6%) had 1, 2 and ≥3 extranodal sites, respectively. The most commonly involved extranodal sites included bone (33.1%), soft tissue (28.6%), stomach (15.0%), intestine (12.8%), and sinus (10.5%). Thirty-two percent, 20%, 0% and 48% of patients with primary extranodal DLBCL had stage I, II, III, and IV, respectively. This is in contrast to 11%, 34%, 26% and 29% for the nodal DLBCL group. Primary extranodal DLBCL was less commonly associated with an elevated LDH (37.6% vs. 53.7%, p=0.001). The distribution of International Prognostic Index scores was similar between the two groups. With a median follow-up of 2.8 years, no significant difference in overall survival was detected between primary extranodal DLBCL and nodal DLBCL analyzed either as a group or by individual stages. Furthermore, we did not identify any specific primary extranodal sites that confer a worse prognosis. Conclusion: In the post-rituximab era, the previously identified survival difference in primary extranodal DLBCL is no longer observed in this large cohort. No significant financial relationships to disclose.
Clinico-pathologic features of lung cancer with EML4-ALK translocation.
Authors: T. Mitsudomi, K. Suda, K. Tomizawa, Y. Yatabe
Journal: Journal of Clinical Oncology (2010)

10598 Background: A small subset of human lung cancer harbors the fusion of the gene for echinoderm microtubule-associated protein-like 4 (EML4) and the gene for anaplastic lymphoma kinase (ALK), resulting from a small inversion within chromosome 2p. A phase I dose escalation trial for ALK tyrosine kinase inhibitor showed promising activity against these tumors. We examined our cohort of patients for EML4-ALK translocation and tried to concentrate this rare type of lung cancer according to the clinico-pathologic background of the patients. Methods: Methods We studied 345 patients with lung cancer who underwent pulmonary resection in our hospital (adenocarcinoma 314, large cell carcinoma 5, small cell carcinoma 1, squamous cell carcinoma 21, adenosquamous cell carcinoma 4) after obtaining appropriate informed consent from the patients. EML4-ALK translocation was detected by RT-PCR and direct sequencing. Results: We found 10 EML4-ALK translocations (3%). Seven were variant 1, two variant 2 and one variant 1. All were adenocarcinoma. Eight patients were female and 7 were never-smokers. None of the tumors harbored either of EGFR, KRAS, HER2 or TP53 mutation. The incidence of ALK fusion was 10 of 97 (10%) without any of four mutations. Median age of patients with ALK fusion was 56 that was significantly younger than that of entire cohort (63) or those with EGFR mutation (64) or KRAS mutation (65). Histopathologically, most of the tumors with ALK fusion were solid-acinar type with cribriform pattern. Conclusions: Lung caners with ALK fusion tended to occur in younger female patients with acinar type adencoarcinoma devoid of EGFR, KRAS, HER2 or TP53 mutations. Although this type of lung cancer is rare, we have to establish efficient screening method because genotype-based therapy would be possible in the near future. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
A phase I study of imexon in combination with docetaxel (DOC) for the treatment of patients with breast, lung and prostate cancer
Authors: S. L. Moulder, N. Dhillon, D. S. Hong, C. S. Ng, L. H. Camacho, E. M. Hersh, K. A. Grenier, M. L. Boytim, R. T. Dorr, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

3589 Background: Imexon (IMX) is a 111 mw cyanoaziridine which induces pro-oxidative apoptotic cell death and is synergistic with several classes of agents including taxanes. Methods: A phase I dose escalation study was conducted in 29 previously treated breast (10), lung (9) and prostate (10) cancer patients (Pts), 10 were previously treated with DOC/DOC adjuvant; 4 also had paclitaxel. DOC dose was 75 mg/m2 on day 1 and escalating doses of IMX from 390–1700 mg/m2 were given on days 1–5 Q3W to cohorts of 3–6 patients. Results: Median age was 61.2 years and median # of prior regimens was 4.1 (1–10). The MTD was 75 mg/m2 DOC and 1,300 mg/m2 IMX. Dose limiting toxicity at 1,700 mg/m2 IMX was transient, grade 3–4 non cardiac chest pain (w/o enzyme elevations or EKG changes) in 3/3 pts with pulmonary metastases. Other toxicities due to DOC were nausea, vomiting and neutropenia. Of the 29 pts 22 were evaluable for response with a PR rate of 14% (2 pts with NSCLC, 1 pt with prostate). 1 pt with breast cancer has had a near PR (26% reduction) and 8 pts have had stable disease up to 7 months. Of 6 pts with prior DOC one withdrew consent, 2 had PD and 3 had SD as best response. Conclusions: IMX can be used at 1300 mg/m2 with full dose DOC to patients with advanced previously treated solid tumors. No increase in toxicity of DOC was noted with addition of IMX. Responses and stable disease were seen in all 3 disease categories including patients who had prior paclitaxel and docetaxel. Further phase II trials of this combination are warranted in these disease categories. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amplimed Amplimed Amplimed Amplimed Amplimed
Randomized, open label, phase III trial of figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC).
Authors: J. Jassem, C. J. Langer, D. D. Karp, T. Mok, R. J. Benner, S. J. Green, K. Park, S. Novello, J. Strausz, A. Gualberto
Journal: Journal of Clinical Oncology (2010)

7500 Background: The Insulin-like growth factor type I receptor (IGF-IR) plays an important role in normal cellular growth and development and is implicated in the regulation of tumor growth. A phase III study was conducted to test the efficacy of the combination of paclitaxel, carboplatin, and figitumumab (CP-751871), a monoclonal antibody targeting the IGF-IR, as first-line treatment of advanced NSCLC. Methods: Eight hundred twenty pts were to be randomized 1:1 to receive paclitaxel (200 mg/m2), carboplatin (AUC = 6), and figitumumab (20 mg/Kg) (PCF) or paclitaxel and carboplatin alone (PC) q3weeks for up to 6 cycles. The primary study endpoint was overall survival (90% power, one sided 0.025 alpha, hazard ratio [HR] 0.77). Results: Accrual has been permanently suspended at 681 pts (median age 62 years, 77% male, 86% squamous cell carcinoma, 88% stage IV, 42% current smokers) enrolled based on a planned interim analysis at 225 events with a HR that crossed the prespecified futility boundary of 1.1 favoring PC. Serious adverse events in the PCF arm included dehydration, hyperglycemia, and hemoptysis. The potential relationship with early death (within 42 days of randomization) of a series of clinical and laboratory parameters was investigated. Low pre-treatment body mass index (p = 0.003) and creatinine clearance (p = 0.1) were predictive of early death for patients receiving figitumumab. Furthermore, PFC/PC survival HR estimates favored PC in pts with low baseline IGF-1 (minimum p = 0.006 for IGF1 < 120 ng/mL; HR 1.6) and PCF in those with high baseline IGF-1 (minimum p = 0.13 for IGF1 > 145 ng/mL; HR = 0.62). Conclusions: Potential subsets of pts with differential safety and efficacy profiles on figitumumab treatment were identified. Additional analyses will be submitted as a late breaking abstract. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer
HIV-associated prostate cancer
Authors: G. C. Bohac, B. J. Dezube, T. P. Cooley, D. Aboulafia, L. Pantanowitz
Journal: Journal of Clinical Oncology (2008)

16089 Background: HIVpositive men being treated with highly active antiretroviral therapy (HAART) are living longer. As a result, these ageing patients are more likely to develop non-AIDS defining cancers such as prostate cancer. The aim of this study was to characterize HIV-infected patients diagnosed and treated for prostate carcinoma. Methods: A retrospective, multi-institutional study involving HIV positive men with concomitant prostate carcinoma. We caputred data on demographics, HIV status, PSA level, symptoms/signs, radiologic findings, Gleason score, stage, cancer treatment, and outcome (response, survival). Data was analyzed using descriptive statistics. Results: 17 patients (8 White, 3 Black, 2 Hispanic, 1 Haitian, 2 unknown race) with HIV-associated prostate carcinoma that were of mean age 59 years (range, 46 to 79). Mean CD4 count was 336 cells/mm3 (range 24 to 759) and mean HIV viral load 17,319 copies/ml (range, undetectable to >100,000). 14 (82%) of these men were receiving HAART. Most patients were diagnosed with carcinoma following an abnormal screening PSA. Mean PSA in this group was 30 ng/mL (range, 4.5 to 77; median 20). Only 6 (35%) men had an abnormal prostate on exam. The mean Gleason score was 6.8 (range 6 to 8), and in most cases cancer was confined to the prostate gland (stage T1 in 64%; 1 case had bone metastases). Most patients were amenable to curative treatment with either hormonal therapy (used alone in 2 cases), radiation (brachytherapy only in 3 cases), and/or prostatectomy (resection alone in 3 cases). Besides hot flushes in 4 men after hormonal therapy, there were no serious side effects. One patient remained untreated. All treated patients had a complete response (undetectable PSA). Most patients were long term survivors. Documented death in 5 cases was unrelated to prostate cancer. Conclusion: Management of HIV-positive men with prostate carcinoma in is becoming increasingly important. Our data shows that in men receiving HAART, their age, PSA levels, clinical presentation, management, and outcome from treated prostate carcinoma does not appear to be significantly altered by HIV status. Therefore, we recommend that patients with prostate cancer and well controlled HIV viremia be managed like their HIV negative counterparts. Further research related to screening for prostate cancer in this setting is required. No significant financial relationships to disclose.
Impact of cyclooxygenase-2 expression on the survival of glioblastoma multiforme
Authors: Y. Choi, D. Kim, H. Lee, W. Hur, K. Kim, Y. Song, S. Choi
Journal: Journal of Clinical Oncology (2007)

12505 Background: Expression of cyclooxygenase-2 (COX-2) protein in glioma patients increased proportionally to the pathologic grade. The extent of COX-2 expression is reported to have an inverse relation to survival rate in glioblastoma multiforme (GBM) patients, but the degree of COX-2 expression in the GBM specimens is variable from study to study. In order to evaluate the degree of COX-2 expression and its effect on survival in GBM patients, we conducted this study. Methods: Between 1997 and 2006, thirty consecutive patients of GBM who were treated with surgery and postoperative radiotherapy (range : 44 ∼ 65.1 Gy, median : 61.2 Gy) were included after exclusion of 3 patients who discontinued radiotherapy before 40 Gy due to mentality deterioration. Expression of COX-2 protein on surgical specimen was examined by immunohistochemistry. Survival analysis and verification were performed in respect to sex, age, resection extent, radiotherapy dose, and degree of COX-2 expression with Kaplan-Meier method and log rank test. Results: The median length of follow up was 13.25 months (6 ∼ 83 months). COX-2 was stained in all patients and COX-2 positives over 75% of tumor cells were found in 24 patients: positive in less than 25% of tumor cells, N = 3 (10.0%); 25 to 50%, 1 (3.3%); 50 to 75%, 2 (6.7%); 75 to 100%, 24 (80.0%). Median survival and 2-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (60 Gy or greater) (p &lt; 0.05). Median survivals of patients with COX- 2 positive in either more than 75% of tumor cells or at most 75% of tumor cells were 13.0 and 15.5 months, respectively (p&gt;0.05), and the 2- year survivals of them were 13.3 and 33.3%, respectively (p&gt;0.05). Conclusions: Eighty percent of the GBM patients were COX-2 positive in more than 75% of their tumor cells. The degree of COX-2 expression in the GBM patients had not a significant impact on survival, but the high positive rate of COX-2 in GBM could be a potential selective target for treatment. No significant financial relationships to disclose.
Re-establishing oncologic care after a major disaster.
Authors: M. A. Sheen, G. Lang-Mims, C. A. Leissinger, R. Kruse-Jarres, M. Barnhill, M. Blaya
Journal: Journal of Clinical Oncology (2010)

e16541 Background: The Medical Center of Louisiana–New Orleans (MCLNO) Hematology/Oncology Clinic closed after Hurricane Katrina from 09/2005 to 10/2007. The clinic reopened in September 2007. We were curious about the patients who presented in the first two years of the clinic reopening. Methods: Information was obtained through IRB-approved chart review of all patients on appointment census for the clinic within the time period. Patients were included if they had documentation of being seen in clinic and were evaluated for sex, age, diagnosis, date of diagnosis, stage at presentation, treatment (if any), date of first post-Katrina clinic visit, number of visits within the time period, number of missed appointments, insurance status, citizenship, and status of displacement after Katrina. Lab, radiology, and chemotherapy visits were omitted from the total number of visits. Results: Over the following dates, an indicated number of patients were seen in clinic: Sept 2007-Nov 2007: 28; Dec 2007-Feb 2008: 56; Mar 2008-May 2008: 63; Jun 2008-Aug 2008: 63; Sept 2008-Nov 2008: 49; Dec 2008-Feb 2009: 46; Mar 2009-May 2009: 59; Jun 2009-Aug 2009: 84. Patient sex: Female: 243 and Male: 205. Diagnoses: Solid Tumor: 286, Malignant Hematology: 59, Benign Hematology: 103. Of the solid tumor diagnoses: Breast: 98, Lung: 58, GI: 46. Patients were staged as: Stage 0: 17, Stage I: 38, Stage II: 51, Stage III: 59, Stage IV: 108, Unstaged/Remission: 67, Other: 5. Insurance status was: Medicaid /Medicare: 211, Free care/ Self Pay: 212, Private: 16, Prisoner: 9. Clinic patients' displaced statuses: Not displaced: 7, Displaced: 31, Unknown: 74, Dx Post-Katrina: 336. The average number of visits per patient was 5.27. Patients failed to show for one of every 2 visits scheduled. Twenty-three patients were undocumented aliens. Conclusions: Over the course of 2 years, the MCLNO Hematology/Oncology clinic saw a large volume of patients. Seventy-five percent of patients were diagnosed after Katrina. The majority of patients who were followed in the clinic before the storm did not return. Based on the above results, improvements for the future of the clinic should focus on follow-up and encouraging early diagnosis and screening. Data collection will continue to determine future trends. No significant financial relationships to disclose.
Final results of randomized study of gemcitabine (G) plus cisplatin (P) versus etoposide (E) plus cisplatin in locally advanced or metastatic non small cell lung cancer (NSCLC)
Authors: A. Bousahba, F. Bereksi-Reguig, F. Seghier, A. Boukerche, A. Dali-Youcef, L. Djellali
Journal: Journal of Clinical Oncology (2008)

19006 Background: We conducted a randomized monocentric study to compare the treatment response of two chemotherapy doublets GP versus EP. Time to disease progression, survival time and toxicity were the secondary endpoints. Methods: Patients with non-operable stage IIIB/IV histological or cytological proven NSCLC, ECOG PS ≤ 2, were randomized to: (A) gemcitabin 1250 mg/m2 on d 1, 8 plus cisplatin 80 mg/m2 on d1 q3w for 6 cycles or (B) cisplatin at same dose followed by etoposid 100 mg/m2 on d 1, 2, 3 q3w. The sample size was estimated at 64 patients per treatment arm to provide a power of 0.80 to detect a 20% difference in response rate between the two groups at the 5% level. Treatment assignments were randomized within two strata on the basis of stage (IIIB vs IV) and performance status (0–1 versus 2). Results: One hundred thirty two chemonaïve patients were enrolled (A: 67, B: 65), median age 59.3 years (arm A) and 58.3 years (arm B), stage IIIB (43.3% A vs 41.5% B), PS 0–1 (71.6% A, 72.3% B). A total of 443 cycles were administered 238 (A) and 205 (B) with a median of 3 cycles per patient in each group. One hundred twenty one patients were evaluable for toxicity, 112 for response (59 pts in A and 53 pts in B). Treatment response in intent to treat principle were respectively in arms A and B: complete response (1.6% - 0%), partial responses (34.8% and 20.3%). The objective response rate was 36.4% (95% CI 24.8%-47.9%) in A, 20.3% (95% CI 10.5%-30.1%) in B, no change (31.8% and 35.9%) and progressive disease (18.2% and 31.3%). Median time to progression: 6.7 months (A) and 6.2 months (B). Median survival: 12.6 months (A) and 9.3 months (B). Incidences of grade 3–4 toxicities were respectively in arms A and B: nausea-vomiting (39.1%-15.8%, p=0.004), alopecia (7.8%-43.9%, p<0.001), neutropenia (11%-40.4%, p=0.0001), thrombopenia (0–1.8%), anemia (10.9–7%). Febril neutropenia occurred in 1.6% (A) and 7% (B). One toxic death occurred in arm B. Conclusions: Compared with etoposid-cisplatin, gemcitabin-cisplatin had a higher activity and a better toxicity profile. No significant financial relationships to disclose.