tbuckley/cabot-search huggingface dataset:
Association of gender and passive smoking with epidermal growth factor receptor mutations in never-smokers with non-small cell lung cancer: A prospective study based on detailed passive smoking questionnaire.
Authors: T. Kawaguchi, M. Ando, A. Kubo, M. Takada, S. Atagi, K. Okishio, K. Asami, A. Matsumura, K. Tsujino, H. Sasaki
Journal: Journal of Clinical Oncology (2010)

7558 Background: Epidermal growth factor receptor (EGFR) mutations occurred frequently in never smokers with non-small cell lung cancer (NSCLC). However, cause of the mutations is unclear. Methods: A total of 126 patients with NSCLC were prospectively included in this study who smoked less than 100 cigarettes during lifetime. Detailed passive smoking information was obtained through questionnaire including exposure period, place (household or work place) and duration. Cumulative dose of passive smoking (CDP) was evaluated as sum of the number of the exposure year per place. EGFR and K-ras mutations were examined using real time polymerase chain reaction amplification (genotyping). Results: One hundred and twenty four patients (98.4%) had the passive smoking history, and the CDP ranged from 0 to 118 (median=50). EGFR mutations were detected in the 83 of 126 patients (36 in-frame deletions in exon 19, 43 mutations in codon 858 in exon 21) and K-ras in the two of 98 patients. The incidence of EGFR mutations was significantly higher in female than in male (70.3%, 33.3%; p = 0.0046), and increased proportionally in the tertile groups separated based on CDP (low group: 56.4%, middle: 60.5%, high: 79.6%; p=0.0250). In the multivariate logistic regression model including gender, CDP and family history of lung cancer, both gender and CDP were significantly associated with the incidence of EGFR mutations; the odds ratio for EGFR mutations were 2.07 (95%CI: 1.17 to 3.85; p = 0.0145) for gender, 1.02 (95%CI: 1.00-1.04; p = 0.0298) for each 1-year increment in CDP, and 1.02 (95%CI: 0.36-3.11; p = 0.9705) for family history of lung cancer. Conclusions: Female gender and longer duration of passive smoking closely associated with epidermal growth factor receptor mutations in never smokers with NSCLC. No significant financial relationships to disclose.
FOLFOX4 as adjuvant therapy in elderly patients (pts) with colon cancer (CC): Subgroup analysis of the MOSAIC trial.
Authors: C. Tournigand, T. Andre, j. Bachet, L. Teixeira, C. Boni, P. R. Clingan, T. Hickish, J. Tabernero, A. De Gramont
Journal: Journal of Clinical Oncology (2010)

3522 Background: In elderly CC pts, adjuvant 5FU-based chemotherapy increases overall survival (OS) and disease-free survival (DFS) (Sargent, NEJM 2001). FOLFOX4 improved DFS and OS in stage III (André, JCO 2009). In a pooled analysis of NSABP-C07 and MOSAIC trials, oxaliplatin/5FU-based chemotherapy was not superior to 5FU/LV in pts ≥ 70 years (Jackson Mc Cleary, ASCO 2009). Methods: We performed a subgroup analysis of pts aged ≥ 70 yrs in the MOSAIC trial, reviewing clinical characteristics, comorbidities according to Adult Comorbidity Evaluation-27, SAEs, 2nd cancer and cause of death. Results: 315 pts ≥ 70 yrs were randomized between FOLFOX4 (155 pts) and LV5FU2 (160 pts). Median follow-up was 6 yrs. DFS hazard ratio (HR) was 0.91; 95% confidence interval (CI) 0.62 to 1.34 and OS HR was 1.10; 95% CI 0.73 to 1.65. No imbalance was observed for initial characteristics. In the FOLFOX4 arm and the LV5FU2 arm, 59 and 66 pts were stage II, 38 and 42 high risk stage II (pT4 and/or < 12 lymph nodes), 96 and 94 pts were stage III, 24 and 29 N2, 85 and 93 pts had grade 1-2 comorbidities, including 74 and 75 pre-existing cardiovascular disease, respectively. 30 pts had a SAE (treatment related 9, cardiovascular 4 and other 19) with FOLFOX4 compared to 15 pts (treatment 3, cardiovascular 2, other 10) with LV5FU2 (p = 0.02). Less patients had surgery of metastases (9 vs. 22; p = 0.01) and irinotecan- or oxaliplatin-based therapy (16 vs. 30; p = 0.01) at relapse in the FOLFOX4 than in the LVFU2 arm. More deaths not CC-related occurred with FOLFOX4 than with LV5FU2 (22 vs. 11; p = 0.043), including second cancer deaths, 9 vs. 1 pts, respectively (p = 0.02). Conclusions: The DFS benefit of FOLFOX4 in elderly pts could be of less magnitude than in the younger population. Lack of OS benefit is not related to initial tumor characteristics or comorbidities, but to different management or outcome of relapses or second cancers. More pts died of second malignancy in FOLFOX4 arm. Higher occurrence of SAEs and difficulties in treatment of relapses argue to reduce the FOLFOX4 duration (IDEA study). An ongoing update and a 10-year follow up will allow the further evaluation of these findings. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Baxter International, Roche, sanofi-aventis Baxter International, Pfizer, Roche, sanofi-aventis sanofi-aventis Roche, sanofi-aventis
Tandem high-dose chemotherapy (HDCT) and peripheral stem cell rescue (PSCR) in patients (pts) with advanced soft tissue sarcomas (STS), Ewing’s/PNET (ES) and rhabdomyosarcoma (Rhabdo)
Authors: F. Valdes, J. H. Doroshow, W. Chow, L. Leong, K. Margolin, R. Morgan, P. Twardowski, Z. Al-Kadhimi, P. Frankel, G. Somlo
Journal: Journal of Clinical Oncology (2005)

9065 Background: To improve progression-free (PFS) and overall survival (OS) a trial of HDCT was conducted in pts with primary high-risk or responding metastatic sarcomas. Methods: Thirteen pts (10 males, 3 females) with ES (7), rhabdo (4), leiomyosarcoma (1) and malignant fibrous histiocytoma (MFH) (1) were accrued from 2/95 through 9/99. Pts initially received induction or salvage chemotherapy with regimens consisting of doxorubicin (D), ifosfamide (I), cyclophosphamide (Cyc), cisplatin (P), vincristine, etoposide, dacarbazine, as well as debulking surgery (9) and radiation therapy (RT) (10). Pts received G-CSF 10μg/kg to procure 14x108 mononuclear cells/kg. Cycle (C) 1 of HDCT consisted of I 14gm/m2 and D 150 mg/m2 administered over 96 hours as an IV infusion, followed by PSCR. C2 consisted of melphalan (M) 75 mg/m2and P 100 mg/m2 on days (d) -11 and -4 followed by PSCR. Results: Eleven of 13 pts completed both cycles of HDCT; 2 pts received C1 only due to reduction in pulmonary function tests and osteomyelitis. No pt died from HDCT. All pts required narcotics for grade 3 mucositis with C1, developed grade 4 neutropenia and required platelet (plt) transfusions. All pts developed neutropenic fever with C1, and 9/11 with C2. The median number of d to neutrophil and plt recovery was 9 (5–18) and 8 (4–31) following C1 and 12 (9–15) and 9 (5–17) following C2. Of the 13 pts enrolled, 2 with advanced ES and 1 with metastatic MFH are alive and free of disease 111, 84 and 60 months post PSCR. The pt with leiomyosarcoma relapsed at 38 months, but was subsequently treated with surgery and RT and is alive at 98 months. The median PFS and OS were 8 and 12 months for pts with rhabdo, and 10 and 22 months for pts with ES. Conclusions: HDCT with D/I followed by M/P is feasible. Although HDCT is unlikely to benefit pts with rhabdo, its role as consolidation therapy in pts with other STS and ES should be assessed in prospective randomized studies. [Supported by NCI Cancer Center Support Grant CA62505] No significant financial relationships to disclose.
Treatment of high-grade astrocytic tumors with the humanized anti-EGF-R antibody h-R3 and radiotherapy
Authors: T. Crombet Ramos, J. Figueredo, M. Catala, S. Gonzalez, J. C. Selva, C. Toledo, O. Torres, R. Perez, A. Lage
Journal: Journal of Clinical Oncology (2005)

2554 The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. EGFR is one of the most widely explored target in cancer. h-R3 is a humanized monoclonal antibody that recognized the EGFR external domain with high affinity. In order to evaluate the safety and preliminary efficacy of h-R3, we conducted a Phase I/II trial using h-R3 in combination with radiotherapy in 24 high-grade astrocytic tumors patients. The primary endpoint of the trial was safety of h-R3 when used at multiple doses in combination with radiation. Secondary endpoint was the preliminary evaluation of the clinical response. This was an open label, uncontrolled, multi-centric Phase I/II clinical trial, in which patients received 6 weekly infusions of h-R3 at the dose of 200 mg in combination with external beam radiotherapy. Immunoscintigraphic studies were done after treatment to evaluate treatment response. Twenty-four patients, were enrolled in the trial. Primary tumors corresponded to glioblastoma multiforme (15 patients) and anaplastic astrocytoma (9 patients). All patients underwent debulking surgery or biopsy before entering the trial. No evidences of grade 3/4 adverse events were detected. One patient developed a serious adverse event that consisted in grade 2 dysphasia and sensory alteration. No acneiform rash was detected. In this patient set, 4 subjects (16.7%) have achieved complete response while 5 patients (20.8 %) have reached partial response. In total, 20 patients (87.5%) achieved disease stabilization or an objective response. Overall survival from trial inclusion has increased after the combined therapy in comparison with the historical figures for standard radiation regimen and chemoradiation schemes. With a median follow up time from treatment beginning to the closeout date of 10.3 months (range 2.57 to 26.13 months), the mean and median survival for all the patients is 16.76 and 14.77 months. No significant financial relationships to disclose.
Relationship between biological and self-reported measures of stress among informal caregivers of patients with prostate cancer
Authors: W. P. Witt, S. Pickard, T. Kuzel, T. McDade, S. Perry, S. Hung, J. Zagory, H. Lin, S. Costello, K. Colella, C. L. Bennett
Journal: Journal of Clinical Oncology (2006)

18506 Background: Informal caregivers of prostate cancer patients often experience chronic psychological stress that may adversely impact their physical and mental health, and their ability to care for their families and the patient. This study aims to determine the association between perceived and biological stress among informal caregivers of prostate cancer patients. Methods: A total of 24 informal caregivers of prostate cancer patients were recruited from both the Jesse Brown VA Center (Lakeside and Westside, Chicago) and the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. Caregivers completed self-reported measures of stress, somatization, life events, burden, health status (SF-36) and mental health. Capillary blood spot samples from caregivers were used to examine two measures of biological stress, Epstein-Barr virus antibody titer and C-reactive protein. Results: Informal caregivers had a mean age of 63 years and were mostly female and spouses of patients with prostate cancer. Many had preexisting co-morbidities, including 45.8% with hypertension, 45.8% with arthritis, and 33.3% with diabetes. Nearly 30% had been hospitalized in the last 12 months. 33.3% of caregivers experienced at least one major life event in the last year and 62.5% had symptoms of somatization illness. Caregivers with symptoms of somatization illness had higher mean Epstein-Barr antibody titers as compared with those without symptoms (Mean EBV antibody titer: 198.3 versus 141.8, respectively (p &lt; 0.05)). Caregiver-reported measures were not correlated with C-reactive protein levels. Caregivers with higher levels of strain perceived more stress in their lives (p &lt; 0.05), but showed relatively high self-esteem (mean = 30.6, SD = 2.8, on a 7–35 scale). Conclusions: These preliminary findings suggest that informal caregivers who report symptoms of somatization illness exhibit signs of relative suppression of the cell-mediated immune processes as a result of the reactivation of the Epstein-Barr virus. Final analyses will be conducted that control for potential confounders and will further elucidate if caregiver stress is associated with suppression of the immune system. No significant financial relationships to disclose.
Phase II trial evaluating concomitant docetaxel and samarium (TAXAM) in patients with hormone refractory metastatic prostate cancer
Authors: A. Widmark, H. Modig, M. Johansson, L. Franzen, L. Johansson, I. Turesson, A. Laurell
Journal: Journal of Clinical Oncology (2005)

4736 Background: New treatment modalities for metastasized hormone refractory prostate cancer are warrented, despite the new data on docetaxel (Taxotere). The publication by Tu and co-workers in Lancet in 2001 indicates astonishing effect by the combination of radioisotope and chemotherapy. To further evaluate the combination of radioisotopes (153Sm; Quadramet) and chemotherapy (docetaxel; Taxotere) we have performed a phase II study to evaluate the combination TAXSAM in HRPC. Methods: Thirty progressing HRPC patients were included in the study. Treatment was given with docetaxel 30 mg/m2 iv. 30 minutes weekly for 5 weeks. 18–24 hours prior to the 4th week treatment with docetaxel, 37 MBq/kg of samarium was injected i.v. The 2nd TAXSAM treatment was repeated at PSA and/or clinical progression. Results: Among 20/30 patients 14 has received the 2:n cycle of treatment, with a median time of 6 months from start of the 1st treatment until start of 2nd treatment. Among the first 20 patients during and after the 1st TAXSAM cycle Grade 3 neutropenia was seen in 2 patients, week 2 and 4 after 153Sm and 1 patient had Grade 4 on week 2 after 153Sm. 1 patient had grade 2 thrombocytopenia 4 weeks after 153Sm. PSA and time to progression and survival will be reported. Conclusions: The result of this phase II study of TAXSAM (5–1) x 2 show low toxicity with good palliative effect lasting 5 months after the 1st cycle. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Beampoint AB, Novartis, Schering AG Aventis, Schering AG
Outcome of allogenic SCT in patients with low left ventricular ejection fraction
Authors: S. Qureshi, F. Bukhari, R. M. Saliba, C. Hosing, R. E. Champlin, S. A. Giralt, M. J. De Lima, S. W. Yusuf, M. H. Qazilbash
Journal: Journal of Clinical Oncology (2007)

7099 Background: High-dose therapy and allogeneic stem cell transplantation (allo SCT) is a potentially curative treatment for patients with hematologic malignancies. Due to a high risk of regimen-related toxicity, only patients with excellent organ-system function are considered eligible for this treatment. A low left ventricular ejection fraction (LVEF) of ≤ 45% is considered to be a major risk factor for post-transplant cardiac toxicity and nonrelapse mortality. However, several patients with advanced hematologic malignancies and low LVEF can potentially benefit from this therapy. To address this issue, we studied the incidence of cardiac toxicity and non-relapse mortality (NRM) in 56 patients with low LVEF undergoing allo SCT. Methods: We performed a retrospective analysis on 56 patients with impaired cardiac function, who underwent an allo SCT between January 2000 and February 2006 at our institution. Pre-transplant evaluation included bidimensional echocardiogram and an electrocardiogram. Cardiac toxicity was defined as congestive heart failure (CHF), atrial / ventricular arrhythmia or acute myocardial ischemia. Twenty-two patients received a myeloablative (16 busulfan-based, 6 TBI-based), while 34 patients received a fludarabine-based reduced-intensity preparative regimen. Results: Twenty-three patients (41%) received allo SCT from an unrelated donor. Acute leukemia was the reason for allo SCT in 32 (57%) patients. Baseline LVEF, within 30 days prior to allo SCT, ranged from 20 to 45%. After a minimum of 6-month follow up, cardiac toxicity was seen in 7 (12%) patients. That included CHF in 4 (7%) and atrial fibrillation (AF) in 4 (7%). One patient had both CHF and AF. There were no documented episodes of acute myocardial ischemia. Cumulative incidence of NRM at 100 days was 12%, none of the deaths being attributable to a cardiac cause. These were comparable to allo SCT performed in patients with normal LVEF. Age, degree of left vetricular dysfunction, type of transplant or the underlying disease did not emerge as significant predictors of post-transplant cardiac toxicity or NRM. Conclusions: Allogeneic SCT is feasible in patients with hematologic malignancies and low LVEF. A prospective study with stratification for cardiac risk factors is warranted in patients with low LVEF. No significant financial relationships to disclose.
A phase II study of gefitinib in combination with FOLFOX-4 (IFOX) in patients with metastatic colorectal cancer
Authors: G. A. Fisher, T. Kuo, C. D. Cho, J. Halsey, C. N. Jambalos, E. J. Schwartz, R. V. Robert, R. H. Advani, H. A. Wakelee
Journal: Journal of Clinical Oncology (2004)

3514
Bioavailability of sorafenib tablets administered as a liquid suspension
Authors: J. T. Lettieri, R. Dubowy, C. Xia, C. Rotolo, M. A. Zinny
Journal: Journal of Clinical Oncology (2009)

e14549 Background: Sorafenib is a multikinase inhibitor currently approved by the FDA for the treatment of advanced renal-cell carcinoma (RCC) and unresectable hepatocellular carcinoma (HCC), and by the EMEA for the treatment of HCC and advanced RCC. Sorafenib is available as a tablet formulation. Some patients who are unable to swallow tablets have suspended sorafenib tablets in a liquid for ease of administration. We performed a study to assess whether this process alters the bioavailability of sorafenib. Methods: Twenty-six healthy male volunteers were enrolled. Utilizing a randomized, crossover design, subjects received either two 200-mg intact tablets (IT) with 8 ounces water, or two 200-mg tablets disintegrated over 10 minutes in 2 ounces of water (ST), with an additional 6 ounces of water swallowed as a rinse of the dosing vessel. Doses were separated by a 10- to 14-day washout period. Following each dose, blood samples were collected at designated times up to 144 hours after dosing for measurement of sorafenib plasma concentrations. Sorafenib was assayed by a validated liquid chromatography/mass spectrometry method. The pharmacokinetic parameters area under the curve (AUC), maximum concentration (C max ) and time to C max (T max ) were assessed by noncompartmental analysis. Results: Geometric mean (percentage coefficient of variation) or median results for these pharmacokinetic assessments are shown in the table. Conclusions: The pharmacokinetics of sorafenib, when administered as a liquid suspension of tablets in water, were similar to the pharmacokinetics of tablets swallowed whole. [Table: see text] [Table: see text]
Community-based trial of pentostatin, cyclophosphamide, and rituximab (PCR) in chronic lymphocytic leukemia (CLL) and small B-cell lymphocytic lymphoma (SLL)
Authors: R. O. Dillman, M. T. Schreeder, J. K. Hon, C. Depriest, P. S. Kennedy, R. J. Green
Journal: Journal of Clinical Oncology (2005)

6685 Background: The alkylating agent cyclophosphamide (C), the purine nucleoside analogues pentostatin (P), and fludarabine (F) and the anti-CD20 monoclonal antibody rituximab (R) are active in CLL and may be synergistic. Single institution combination therapy trials produced response rates of 75% in previously treated CLL for FC and PC, and 90% for FCR and PCR in untreated CLL. Methods: We initiated a multi-center PCR trial with P at 4 mg/m2, C at 600 mg/m2, and R at 375 mg/m2 (all iv) for up to 6 cycles at 3-week intervals. Patients were not eligible if they had prior therapy with combination alkylating agent or monoclonal antibody with a purine analogue or prior P. Allopurinol, hematopoietic growth factors, bacterial and viral prophylaxis were strongly recommended as supportive therapy. NCI criteria were used to assess response rates and toxicity. Results: 21 patients (median age 69 years), completed therapy after receiving an average of 4 cycles of PCR. 15 patients completed the first 3 cycles; 8 completed all 6 cycles. After 3 cycles there were 2 CR, 7 PR, 6 SD, and 0 PD. One SD became a PR after 6 cycles for an overall objective response rate of 48%. The response rate was 8/12 in patients who had received no prior therapy and 2/9 in patients who had received prior therapy for CLL. 4 patients were removed from study early because of possible therapy-related toxicity: death from pneumococcal sepsis after cycle 2 in a 76 y/o M who was not neutropenic; heart failure attributed to a silent myocardial infarction in a 65 y/o F after cycle 2, renal insufficiency after cycle 1 in a 77 y/o M, and acute renal failure and eventual death after cycle 2 in a 73 y/o F. One patient who had experienced no toxicity withdrew after 2 cycles, and one patient was removed from study after one cycle because of non-compliance. Only 2 patients had grade 4 hematologic toxicity (granulocytopenia). Highest average toxicity grade was 1.96 for nausea/vomiting. Conclusions: This treatment regimen is tolerable and active in CLL, but should be used with caution in elderly patients, with special attention to the increased risk of P-related toxicity associated with decreased urinary clearance. [Supported by SuperGen, Inc.] No significant financial relationships to disclose.
Denying the incredible: unexplained deaths in a Veterans Administration hospital
Authors: P Kroll, K Silk, K Chamberlain, R Ging
Journal: American Journal of Psychiatry (1977)

During July and August 1975 a large number of patients at the Ann Arbor Veterans Administration Hospital experienced unexplained respiratory arrests, and there were six deaths. These were later shown to be due to the deliberate injection of pancuronium bromide, a muscle relaxant. A questionnaire survey of the reactions of the hospital patients and staff to the deaths revealed that the patients had more confidence in the hospital and their medical treatment than did the staff, and those patients who were theoretically most vulnerable used denial to cope with the unprecedented and frightening situation.