tbuckley/cabot-search huggingface dataset:
A phase I study of docetaxel and bexarotene
Authors: R. Suresh, W. Read, P. M. Fracasso, R. Govindan
Journal: Journal of Clinical Oncology (2004)

3200 Background: Docetaxel has activity against wide range of tumors and bexarotene is a specific ligand for the retinoid X receptor (RXR) approved for use in cutaneous T cell lymphoma. The combination of vinorelbine, cisplatin and bexarotene has been shown to have encouraging activity in non-small cell lung cancer (NSCLC). Methods: We are conducting the phase 1 study of docetaxel and bexarotene in patients with advanced resistant malignancies to define the maximum tolerated dose of bexarotene that could be administered daily in combination with weekly docetaxel. Patients receive docetaxel 25mg/m2intravenously (IV) every week for 3 weeks followed by one-week rest every 28 days. Bexarotene dose was started at 200mg/m2 orally (PO) once a day beginning d1 and continued for the entire duration of study in the absence of significant toxicity or disease progression. All patients received atorvastatin at 10 mg/day starting day 1 of the study or before. Atorvastatin doses were adjusted based on weekly triglyceride levels using an established algorithm. Our plan is to escalate only the doses of bexarotene in three cohorts (cohort 1: 200 mg/m2, cohort 2: 300 mg/m2 and cohort 3: 400 mg/m2) using the modified Fibonacchi scheme. Results: We have enrolled 6 patients, three each in cohorts 1 and 2 without experiencing any dose limiting toxicity. Patient Characteristics: Median age 54 years, Female 4, histological type: NSCLC 3, renal cell cancer 1, gastric cancer 1, and angiosarcoma 1. Median number of previous chemotherapy regimens 1 (Range 1–2). Median cycle of treatment delivered 2 (range 2–3) Toxicities: No dose limiting toxicities have been experienced so far. Only grade 3 toxicity: hypertriglyceridemia 1 pt. Response: objective response none, stable disease 1, disease progression 3, patient withdrawal 1. Conclusion: Combination of docetaxel and bexarotene is well tolerated and accrual to the final cohort is continuing. Updated results will be presented at the annual meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Pharmaceuticals Aventis; Bristol-Myers Squibb; Lilly; Ligand; Pfizer
Carboplatin (C) plus paclitaxel (P) versus carboplatin plus pegylated liposomal doxorubicin (PLD) in patients with advanced ovarian cancer (AOC): Final analysis of the MITO-2 randomized multicenter trial.
Authors: S. Pignata, G. Scambia, A. Savarese, R. Sorio, E. Breda, F. Legge, V. Gebbia, P. Musso, C. Gallo, F. Perrone
Journal: Journal of Clinical Oncology (2010)

LBA5033 Background: CP is standard first-line chemotherapy for AOC. MITO-2 (Multicentre Italian Trials in Ovarian Cancer) is an academic multicenter randomized phase III study, testing whether C-PLD is more effective than CP. Methods: AOC chemo-naïve patients (pts), stage IC-IV, aged≤75, ECOG PS≤2, were randomized to CP (C AUC5 + P 175 mg/m 2 ,d1q3w) or to C-PLD (C AUC5 + PLD 30 mg/m 2 ,d1q3w), both for 6 cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate, toxicity and quality of life (QoL). To have 80% power in detecting a 0.80 HR in PFS, with 2-sided α error 0.05, 632 events were needed and 820 pts were planned. Response rate and toxicity have been reported at ASCO 2009 (abs #LBA5508). All analyses are based on intention to treat. Results: From Jan ’03 to Nov ’07, 820 pts were randomized, 410 to each arm. Median age was 57 yrs (range 21-77). Stage III (60%) and IV (21%) were prevalent. A plateau in PFS events was reached before obtaining the planned number. Thus, following an IDMC recommendation, the final analysis was done with 556 events occurred as of December 31, 2009. This size is consistent with HR to be detected equal to 0.79, with 80% power. With a median follow-up of 40.2 months, median PFS was 19.0 and 16.8 months with C-PLD and CP, respectively (HR 0.95, 95%CI 0.81-1.13, log-rank p value=0.58). Lack of significant difference was confirmed (HR 0.96, 95%CI 0.81-1.14) at multivariable analysis adjusted by stage, PS, residual disease, age and size of the institution. There was no heterogeneity of treatment effect among major subgroups. With 313 deaths recorded, median OS was 61.6 and 53.2 months with C-PLD and CP, respectively (HR 0.89, 95%CI 0.72-1.12, log-rank p value=0.32). QoL data will be presented at the meeting. Conclusions: In the MITO-2 trial, C-PLD was not found to be superior to CP, which remains the standard first-line chemotherapy for AOC.However, given the observed confidence interval and the different toxicity profile, C-PLD could be considered an alternative to standard therapy. Study was partially supported by Schering-Plough. [Table: see text]
A retrospective study on surveillance behavior and prophylaxis after genetic testing for hereditary breast and ovarian cancer in Hong Kong Chinese families.
Authors: A. Kwong, A. T. Chu, C. T. Wu, C. H. Wong, E. Y. Tsui
Journal: Journal of Clinical Oncology (2010)

e12017 Background: Studies in the West have shown that the uptake rates of surveillance and prophylaxis may be different in BRCA mutation carriers and non carriers and this may vary between different ethnicities. To date there is no data available for the behavioural pattern of Asian cohorts. The present study is the first to investigate the behavioural impact and medical compliance in Hong Kong Chinese high risk families who had undergone BRCA1 and BRCA2 genetic testing up to 1 year after genetic testing. Methods: 61 individuals who had BRCA1 and BRCA2 genetic testing previously performed by the Hong Kong Hereditary Breast Cancer Family Registry were surveyed by a face-to-face or telephone interview. Sociodemographic information, genetic test results, pre-and post-testing surveillance, medical regimes, and attitudes towards clinical management were obtained by interviews and retrieval of medical records using a prospective database. Results: 35 carriers and 26 noncarriers of a BRCA 1/2 mutations were interviewed. 71.4% of carriers and 88.5% noncarriers had cancer prior to testing. The take-up rate of clinical breast examination and mammography by female carriers (75%) and noncarriers (82.6%) remained high after knowing the test results. 31.6% and 17.4% of the eligible carriers had prophylactic mastectomy and oophorectomy respectively. 66.7% of carriers (40% of noncarriers) underwent ovarian surveillance. Interestingly, 14.8% of carriers (15.4% of noncarriers) added Chinese medicine as complementary treatment after knowing the genetic test result. Clinicians' advice was perceived as the major reason of choosing a particular surveillance strategy. Conclusions: As population-based breast and ovarian screening is unavailable in Hong Kong, the relatively high take-up rate of screening among noncarriers may be the enhancement of health-consciousness as a result of cancer experience. Proper education by clinicians is crucial for high-risk Chinese patients due to the cultural characteristic of medical compliance. A prospective study will contribute to the understanding of attitude-change towards clinical management of this population. No significant financial relationships to disclose.
Trastuzumab (T) treatment beyond progression in metastatic breast cancer (MBC): Patterns of care in Swiss clinical practice.
Authors: B. Thurlimann, C. Rochlitz, S. P. Aebi, U. Güth, R. von Moos, A. Müller, L. U. Von Rohr, M. Baumann, J. B. Huober
Journal: Journal of Clinical Oncology (2010)

1146 Background: T is an established therapy for HER2-positive MBC as monotherapy or as part of combination with several chemotherapies (CT). T beyond progression (after first-line T-based therapy) seems to be a frequently used treatment option. We analyzed treatment strategies in pts with HER2-positive MBC over several lines of therapy. Methods: Six Swiss breast cancer centers participated in this retrospective cohort study. Pts with HER2-positive MBC progressing after T (January 2006 to December 2007) were eligible. Data collection included type and duration of anti-HER2 therapy and time to progression (TTP) for each line. Results: All 72 pts (median age 58 years, range 28-81) received T as first anti-HER2 therapy. Combination therapy with T/CT was preferred over T monotherapy (49 vs. 23 pts). T was combined with vinorelbine in 23, with taxanes in 22 and with other CT in 4 pts. In first- line, TTP for both nontaxane and taxane combinations was 35 weeks. After progression, 67 pts received second-line T-based therapy and 1 pt had lapatinib + capecitabine. The majority (51/67 pts) received a T/CT combination with vinorelbine in 27 pts, taxanes in 18 pts and with other CT in 6 pts. Second-line T/CT consisted of the same combination as in first-line in 8/51 pts. Other second-line treatments were: T monotherapy 5 pts, T/endocrine therapy 5 pts, CT 4 pts and endocrine therapy 2 pts. Pts received a median of 4 lines of anti-HER2 therapy (range 1-12); median total duration of anti-HER2 therapy was 20 months (range 1-61). Cerebral metastases at any time during course of disease were observed in 31/72 pts. Conclusions: Durable responses can be achieved with repeated exposure to T irrespective of type of additional CT. T monotherapy was used in a third of pts in the firsst-line setting. Treatment beyond progression with T/CT was the preferred anti-HER2 therapy in second-line. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, GlaxoSmithKline, Roche Roche GlaxoSmithKline, Roche GlaxoSmithKline, Roche
FDG-PET versus Thallium-201 SPECT in the evaluation of putative CNS lymphoma in AIDS patients
Authors: E. Vidan, L. Kostakoglu, M. Coleman, D. Jillapalli, S. M. Philips, J. Leonard, S. J. Goldsmith
Journal: Journal of Clinical Oncology (2006)

1537 Background: The evaluation of CNS lesions in AIDS patients is challenging as both CNS lymphoma and non-neoplastic lesions can have similar clinical presentations and imaging findings. Both Tl-201 SPECT and FDG PET imaging have been used to differentiate malignancy from infection. This study investigates the accuracy of FDG PET compared to Tl-201 SPECT in the diagnosis of CNS lymphoma in patients with AIDS-associated CNS lesions. Methods: Nine patients with AIDS who were found to have rim enhancing brain lesions on MRI underwent both Tl-201 SPECT and FDG PET imaging prior to diagnosis. Diagnosis was made by stereotactic brain biopsy in 6 pts and clinical follow-up in the remaining 3. FDG PET of the brain was performed using a dedicated PET/CT instrument (GE Discovery) 1 hour after 444 MBq FDG. Brain SPECT was performed on a dual head gamma camera (GE Hawkeye) with 185 MBq Tl-201. Images were reviewed along with MRI for anatomic correlation by 2 experienced nuclear medicine physicians blinded to the diagnosis. Results: 43 MRI lesions in 9 patients were evaluated. Clinically, 5 pts (18 lesions) were diagnosed with lymphoma (4 biopsy proven, 1 with known history of lymphoma), and 4 pts (25 lesions) were diagnosed with toxoplasmosis (2 with negative biopsies for malignancy, 2 with clinical course consistent with toxoplasmosis). FDG PET had true positive results for lymphoma in 5 of 5 pts, while Tl-201 SPECT was true positive in only 2 of 5. FDG PET had true negative results in 4 of 4 pts with toxoplasmosis, while Tl-201 had false positive results in 2 of 4. FDG PET had positive and negative predictive values of 100%, while Tl-201 SPECT had PPV 50% and NPV 40%. On a lesion basis, PET showed increased uptake of FDG in 8 of 18 brain lesions in patients with lymphoma, while SPECT showed increased uptake of Tl-201 in 4 of 18 lesions. Tl-201 was positive in 2 lesions in patients diagnosed with toxoplasmosis, while FDG had no false positive lesions. Conclusion: In this limited study, FDG PET proved to be superior to Tl-201 SPECT in the differentiation of CNS lymphoma from toxoplasmosis (overall accuracy 100% vs 44%, respectively). With the increasing availability of FDG PET, this test should probably supplant Tl-201 SPECT as the study of choice following conventional imaging (CT, MRI) of CNS lesions in AIDS patients. No significant financial relationships to disclose.
LSC 2014 abstract - Epithelial to mesenchymal transition in the airway epithelium from COPD patients: Correlation to disease severity
Authors: Sophie Gohy, Bruno Detry, Myriam Polette, Chantal Fregimilika, Caroline Bouzin, Héloïse Gaide Chevronay, Chirstophe Pierreux, Cloé Hupin, Birgit Weynand, Maha Ladjemi, Charles Pilette
Journal: European Respiratory Journal (2014)

Rationale: In chronic obstructive pulmonary disease (COPD), epithelial changes and subepithelial fibrosis are salient features in the airways. Epithelial to mesenchymal transition (EMT) has been suggested in COPD, mainly in alveolar epithelial cells.

Objectives: To evaluate the presence of EMT in the airways and primary air-liquid interface cultures of bronchial epithelial cells (ALI-HBEC) from COPD patients.

Methods: Surgical lung tissue of COPD and control patients (n=49) and ALI-HBEC cultures (n=57) were assessed for EMT markers by immunohistochemistry, western blot and real-time qPCR. Mesenchymal functionalities of ALI-HBEC were assayed through fibronectin release and wound repair.

Results: The bronchial epithelium from COPD patients, as compared to non-smoker controls, showed increased vimentin expression in large and small airways and correlated with airway obstruction (FEV1, FEV1/VC ratio and DLCO). In addition, epithelial E-cadherin and zonula occludens-1 (ZO-1) were decreased in large airways. Increased epithelial vimentin expression correlated to subepithelial deposition and basement membrane thickness in COPD thick slices. The COPD bronchial epithelium displayed similar features in vitro and correlated also to lung function. Moreover, COPD ALI-HBEC showed mesenchymal functions such as extra-cellular production of fibronectin and impaired migration during wound repair.

Conclusions: The bronchial epithelium from COPD patients displays EMT features in lung tissue, which correlates to disease severity and which are recapitulated in primary cultures in ALI conditions. We propose that this abnormal epithelial programming contributes to peribronchial fibrosis in COPD.
A phase I/II study of increasing doses of epirubicin (E) and docetaxel (D) plus pegfilgrastim (Pegf) for locally advanced (LABC) or inflammatory breast cancer (IBC): NCIC CTG MA.22.
Authors: M. E. Trudeau, M. J. Clemons, R. A. Dent, H. J. Kahn, A. M. Parissenti, J. W. Chapman, P. O'Brien, R. A. Jong, K. I. Pritchard, L. E. Shepherd
Journal: Journal of Clinical Oncology (2010)

629 Background: To determine optimal doses and dosing intervals for first-line anthracycline/taxane chemotherapy, we treated women with LABC/IBC with neoadjuvant E and D with Pegf support in sequential phase I dose escalation/phase II schedules at 3- or 2-wkly intervals. Methods: The primary objective was clinical response rate (cRR; complete or partial response [CR/PR by RECIST criteria]); secondary objectives were pathologic complete response rate (pCR in breast and axillary nodes), toxicity, and biomarkers of response, sensitivity/resistance to E/D chemotherapy and relapse-free survival. We report here cRR, pCR and acute toxicities. For the q3 wk cohort (Sched A) phase I dosing began at 75 mg/m2 for E and D and increased per/≥ 3 patients (pts) cohort until dose limiting toxicity (DLT). The phase II dose was at DLT-1 level. Similarly, q2 wk (Sched B) phase I dosing began at 50 mg/m2 for E and D and increased to DLT. Results: A total of 93 pts with LABC/IBC (IBC n = 7) were enrolled on study. Sched A phase I (n = 16), phase II (n = 31); sched B phase I (n = 16), phase II (n = 30). All were evaluable for response and treatment toxicity. The phase II doses were determined as Sched A 105 mg/m2 E, 75 mg/m2 D; Sched B 60 mg/m2 E and D. The median age (yrs) for this trial was 46 (37 for Sched B, phase I). The cRR and pCR rates for the phase II cohorts were: Sched A cRR 90%, pCR 6%; Sched B cRR 93%, pCR 0%. Sched A, 45/46 completed treatment: one stopped for adverse event (AE); for Sched B 33/46 completed treatment: five stopped for AEs, six for progressive disease. DTLs were febrile neutropenia (FN) and diarrhea for Sched A and fatigue for Sched B. For the phase II cohorts toxicities included FN, diarrhea, constipation, sensory neuropathy and fatigue, each in a small number of pts. Conclusions: E/D with Pegf support is highly active in LABC/IBC with respect to clinical response with cRR ≥ 90% on 2- or 3- wkly schedules. However, pCR rates were low, related potentially to age, bulk of disease or tumour characteristics, including inherent or acquired resistance to E/D. Further analyses of predictive and prognostic markers and gene microarrays are ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Pfizer, sanofi-aventis Pfizer, sanofi-aventis Amgen, sanofi-aventis
Preliminary results from a phase II study of celecoxib plus chemotherapy in patients with untreated advanced NSCLC
Authors: J. Wang, X. Liu, L. Yang, Q. Guo, L. Yang, J. Zhao, M. Wu, T. An
Journal: Journal of Clinical Oncology (2007)

18188 Background: Preclinical studies indicated that cyclooxygenase-2(cox-2) inhibitor celecoxib may enhance antitumor efficacy of cytotoxics, and combination with chemotherapy had acceptable tolerability in a phase I trial. This phase II trial evaluated the efficacy and safety of the celecoxib plus platinum-based chemotherapy in advanced NSCLC as first-line chemotherapy. Methods: Patients: chemotherapy naïve, IIIB (w/malignant effusion) IV, PS 0–2; treated with platinum-based chemotherapy (Gemcitabine 1,200 mg/m 2 d1, 2, Cisplatin 75 mg/m 2 d1 Q3w or Docetaxel 35 mg/m 2 d1,8,15, cisplatin 75 mg/m 2 d1, Q4w), and plus celecoxib 400 mg p.o. bid., until evidence of disease progression or toxicity. Primary endpoint: median survival; secondary endpoints: response rate and toxicity. Results: From 3/05 to 6/06, 30 pts with cox-2 positive expression detected by ICH were treated; 27 evaluable for response and toxicity; M/F: 18/12; median age 64 (42–74); PS 0/1/2: 3/23/4; Path: adeno/squamous: 60%/40%; StageIII/IV: 35%/65%. Toxicity: Grade 3 or 4 neutropenia and thrombocytopenia were observed in 40% (11/27) and 30%(8/27) patients, respectively. One patient death was considered possible treatment related. Response: CR:0; PR: 14 (52%; 95% CI 32%-76%); SD: 6 (22%; 95% CI 14%-32%); PD:7 (26%; 95% CI 19%-36%). Median duration of response and stable disease: 6.4 (range 3.5–7.5) and 3.5 months (range 1.5–8.0), respectively. Survival is too early to evaluate. Conclusions: Celecoxib in combination with platinum-based chemotherapy appears to be well tolerated and demonstrates encouraging activity in patients with previously untreated advanced NSCLC. Accrual is continuing to 40 patients and updated response and survival data will be presented. No significant financial relationships to disclose.
A phase I trial of a multi-epitope cancer vaccine (EP-2101) in non-small cell lung (NSCLC) and colon cancer patients
Authors: G. Y. Ishioka, M. L. Disis, M. A. Morse, C. C. Cunningham, H.-J. Lenz, R. A. Figlin, R. W. Chesnut, J. Fikes
Journal: Journal of Clinical Oncology (2004)

2525 Background: Effective vaccines that mediate clinical responses in cancer patients may require generation of broadly specific cytotoxic T lymphocytes (CTLs) directed against multiple epitopes and tumor-associated antigens (TAAs). The EP-2101 vaccine was designed to induce CTLs against epitopes in carcinoembryonic antigen (CEA), p53, HER-2/neu, and MAGE 2/3, four TAAs frequently over-expressed in NSCLC and colon cancer. Using a rational epitope identification process, 2 epitopes from each TAA were selected for vaccine development. All 8 epitopes displayed high HLA-A2 supertype binding affinity and immunogenicity in a primary in vitro induction assay. Six of the epitopes were analogs containing a single substitution which either enhanced MHC binding or stimulated heteroclitic T cell activation, and 2 epitopes were native sequences. The 8 epitopes together with CAP1–6D, a previously described heteroclitic CEA analog, and the PADRE helper T cell epitope were emulsified in Montanide ISA51 adjuvant and tested for safety and immunogenicity in HLA-A2+ NSCLC (stage IIb/IIIa) and colon (stage III) cancer patients with no detectable disease following standard treatment. Methods: Patients received 6 EP-2101 treatments at 3 wk intervals, at a dose of 5 mg total peptide (0.5 mg/epitope). CTL responses in the peripheral blood of patients were measured using a validated interferon-gamma (IFN-γ) ELISPOT assay. Results: Based on 7 patients who have completed treatment (4 colon, 3 lung), EP-2101 appears to be safe and well-tolerated. To date, IFN-γ-secreting CTL responses were observed in all three patients tested, with 1, 4, and 6 epitope responses being detected respectively. Vaccine responses against 1 native epitope and 5 analog epitopes in EP-2101 have ranged from 23–260 net spots/50,000 cells with <8 net spots detected in pre-vaccination samples. Conclusions: A cancer vaccine delivering 9 TAA epitopes can simultaneously induce CTL responses against multiple epitopes and TAAs in patients. This vaccine consisting of native and analog epitopes may provide effective immunotherapy in patients with diverse types of cancer expressing common TAAs. No significant financial relationships to disclose.
Association of serum cytokines with pulmonary tuberculosis treatment outcomes
Authors: Harshita Gupta, Surya Kant, Sushmita Singh, Amita Jain, Kishore Srivastava
Journal: European Respiratory Journal (2014)

Background: The different treatment outcomes of pulmonary tuberculosis (TB) are likely to result from a complex interaction between the host and the pathogen. Aim: To determine the association of serum cytokine concentration with clinical, radiological and drug-susceptible outcomes of active pulmonary TB patients. Method: A hospital based prospective follow-up study design was conducted in two urban centers in Lucknow (UP), India under Directly Observed Treatment Short-course. Newly diagnosed Acid-fast Bacilli (AFB) positive cases between the age group of 12 to 65 years were enrolled. Each participant was interviewed and completed a structured questionnaire to provide demographic information. Outcomes were evaluated by clinical, radiological and drug-susceptibility testing. The immunological parameters were used to assess the levels of IL-2, IL-4, IL-10 and IFN-γ. Results: A total of 185 newly diagnosed patients were recruited. Out of these, 92.4% AFB-positive patients completed the study. The mean(±SD) age was 29(±12) years. There was significant (p=0.03) differences in the concentration of IL-4, IL-10 and IFN-γ at six month between the patients with complete and incomplete radiological clearance. Out of AFB smear positive patients, 91.2% were culture positive and subjected to drug-susceptibility test. Of these, 82.6% isolates were sensitive to all the drugs and 17.3% isolates were resistant to any drug. The IL-2, IL-4, IFN-γ and IL-10 concentrations were significantly (p=0.05) different between drug sensitive and resistant patients at six month. Conclusion: This study concluded that increased IL-4 production associated with the patients to be incomplete radiological clearance and drug resistant.