tbuckley/cabot-search huggingface dataset:
Safety profile of efaproxiral (RSR13), a novel radiation sensitizer, in patients undergoing radiation therapy
Authors: B. Stea, A. Nabid, J. Kresl, W. Roa, L. Mechtler, N. Senzer, I. Germain, C. L. Kass, E. Shaw, J. Suh
Journal: Journal of Clinical Oncology (2004)

3090 Background: Tumor hypoxia is known to decrease radiation sensitivity of solid tumors. RSR13, a novel radiation sensitizer, is an allosteric modifier of hemoglobin. RSR13 reduces the oxygen-binding affinity of hemoglobin to facilitate the release of oxygen, leading to an increase in tumor oxygenation. Methods: A total of 538 patients across phase 1 through phase 3 clinical trials have received at least 1 dose of RSR13 as sole adjunct to radiation therapy (RT). Patients were dosed daily up to 100 mg/kg/d RSR13, 5 days a week for up to 32 doses, immediately prior to RT. Due to the pharmacodynamic effect of RSR13, and to maximize oxygen saturation, all patients received supplemental oxygen during RSR13 and RT treatments. Results: Eight treatment-emergent adverse events have been identified as components of the RSR13 safety profile: nausea/vomiting, headache, hypoxemia (hypoxia), hypotension/dizziness, infusion symptoms, rash/allergic reaction, anemia, and renal dysfunction. The majority of the hypoxemia events were asymptomatic, consisted of low pulse oximeter (SpO2) measurements alone, and were treated with increased supplemental oxygen (increased duration or flow) only. Non-hypoxemia events were typically treated with supportive care (eg, hydration, antihistamines, or antiemetics). Overall 11% of the patients treated in these studies developed a Serious Adverse Event related to RSR13. Conclusions: The use of RSR13 was well tolerated in patients with various solid tumors receiving RT. Events of the RSR13 safety profile were typically reversible and managed with supportive care alone. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allos Therapeutics, Inc. Allos Therapeutics, Inc. Allos Therapeutics, Inc. Allos Therapeutics, Inc.
A phase II clinical trial of gemcitabine and imatinib mesylate for patients with recurrent non-small cell lung cancer (NSCLC)
Authors: M. Eleff, M. A. Sovak, D. Greenberg, L. Guensch, P. Joyce, S. Schwartz, L. Zheng, J. Aisner
Journal: Journal of Clinical Oncology (2008)

19101 Background: Preclinical data demonstrated improvements in response when gemcitabine and imatinib mesylate (imatinib) were used in combination compared to gemcitabine alone. Phase I data from our institution demonstrated tolerable toxicity and promising activity of this combination in patients with NSCLC. We thus started a phase II trial to further explore this combination. Methods: Eligible patients with recurrent NSCLC who received 1 prior chemotherapy regimen, ECOG PS of 0–1, and no prior exposure to gemcitabine or imatinib were treated with gemcitabine 1000 mg/m2 fixed-dose rate infusion on d3 and d8 and imatinib 400 mg orally daily d1–5 and d8–12 on a 21 day cycle. Toxicity was evaluated weekly, with tumor assessment every 2 cycles. The primary endpoint was the RECIST based response rate. This Cancer Institute of New Jersey network, 2-stage, phase II clinical trial planned to enroll 31 patients in the first stage. Results: From 4/06 to 10/07, seventeen patients were enrolled; 10 women; 15 are caucasian. An unplanned toxicity evaluation was performed when it was noted that many patients required early dose reductions. Eight patients (50%) required dose reductions in cycle 2 for hematologic toxicity (grade 3/4 thrombocytopenia, n=4; grade 3/4 neutropenia, n=3; grade 3 neutropenic fever, n=1). An additional 2 patients required dose reductions in cycle 3 for grade 3 (n=1) and grade 4 (n=1) neutropenia. Of the remaining 7 patients, 2 patients discontinued therapy by cycle 2 for nonhematologic toxicity, 4 progressed, and 1 continues on treatment at this time. Out of a total of 37 cycles of treatment, 13 dose reductions were required. Reasons for discontinuation of therapy include; progression of disease (n=1), adverse events (n=1), death not related to treatment (n=1) and other (n=3). Five patients experienced stable disease, 9 progressed, 2 are not yet assessed, and 1 remains on study. Conclusions: Although manageable, there appears to be synergistic toxicity when gemcitabine and imatinib are used in sequential combination to treat patients with recurrent NSCLC. Although some stable disease was seen, this combination seems too toxic for a 2nd- line NSCLC regimen, and further accrual was discontinued. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
Zoned Immune Suppression of Lymph Nodes Draining Malignant Melanoma: Histologic and Immunohistologic Studies&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A J Cochran, E Pihl, D R Wen, D S Hoon, E L Korn
Journal: JNCI Journal of the National Cancer Institute (1987)

Node-to-node heterogeneity of reaction and recognizable patterns of reaction in node groups draining melanoma were sought. Nodes from 72 patients undergoing lymphadenectomy for high-risk, primary melanoma (57) or node-spread melanoma (15) were accurately oriented to the nearest melanoma. Reactivity of paracortex, follicular areas, and sinuses was assessed on a 0-3+ scale. Reactivity was prominent in paracortex and sinuses but varied from node to node within node groups. Nodes nearest to tumor showed least reaction; nodes at intermediate distances from tumor were most reactive, while those farthest away showed mostly little reaction. Variation of nodal reaction that correlated with the node position relative to the nearest melanoma (zoned reaction) was seen in 92% of patients with nodal metastases of melanoma and in 64% of patients with primary malignant melanoma. Follicular and sinusoidal reactions showed no significant zoning. S-100 protein-positive paracortical dendritic cells (PDCs) in tumor-oriented nodes were quantified. PDCs were infrequent in nodes partly replaced by melanoma or located near to melanoma but were numerous in nodes located farther from tumor. Changes of nodal activity (relative stimulation or suppression) correlate with the distance of the node from the nearest deposit of primary or metastatic melanoma.
Association of MGMT-535G&gt;T polymorphism with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy.
Authors: Y. Chae, J. Kim, S. Sohn, B. Kang, H. Ryoo, S. Bae, G. Choi, J. Baek, Y. Kim, Y. Cho
Journal: Journal of Clinical Oncology (2010)

e14067 Background: The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer. Methods: A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR-RFLP assay. Results: During the median follow-up duration of 15.9 (2.1-53.0) months, 67 (71.3%) progression and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) −535G>T polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG+GT genotypes (HR = 3.137; 95% CI = 1.423–6.914; p = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101-6.392; p = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (OS) (HR = 0.229 and 0.205; p < 0.001 and 0.001, respectively). Conclusions: The MGMT -535G>T polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy. No significant financial relationships to disclose.
Blood Pressure Control and Recurrence of Intracerebral Hemorrhage—Reply
Authors: Alessandro Biffi, Jonathan Rosand
Journal: JAMA (2016)

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Phase III study of BEC2/BCG vaccination in limited disease small cell lung cancer (LD-SCLC) patients, following response to chemotherapy and thoracic irradiation (EORTC 08971, the SILVA study)
Authors: G. Giaccone, C. Debruyne, E. Felip, M. Millward, G. D'Addario, L. Thiberville, L. Rome, P. Zatloukal, C. Legrand
Journal: Journal of Clinical Oncology (2004)

7020 Background: Attempts to maintain the response to initial therapy have been unsuccessful in SCLC. BEC2 is a murine IgG2b antibody that elicits antiidiotypic response to GD3, a glycosphingolipid overexpressed on membranes of SCLC and other tumors derived from the neural crest. In a pilot study (Grant et al. Clin Cancer Res 1999) long-term survivors were reported in SCLC patients vaccinated with BEC2/BCG. Methods: LD-SCLC patients in response after 4–6 cycles of multi-agent chemotherapy and thoracic irradiation were eligible. PCI was recommended in complete responders. Patients were randomized to observation or to 5 BEC2 (Merck KGaA and ImClone Systems Inc.) vaccinations (2.5 mg by 8 intradermal injections) with BCG, given on week 0, 2, 4, 6 and 10. A total of 376 deaths were required to detect a 40% increase in median survival in the V arm using a 2-sided α of 5% and a 90% power. The protocol was amended after 55% of inclusions to allow patients with a PPD positive test, when this was found to be safe (Klimek et al, ASCO 2000).Results: From April 1998 to October 2002 515 patients were randomized to observation (O, n=258) or vaccination (V, n=257). Arms were well balanced; 38% female, Karnofsky PS >80% in 94%, PPD positive in 11%, complete response to initial therapy in 49%, sequential chemotherapy-thoracic irradiation in 40%; 62% received PCI. The most frequent treatment related side effect was local reaction at the injection sites (95% of patients, grade 3 in 35%). Lethargy was observed in 37% (grade 3 in 3%). Six toxic deaths have been reported, 4 in the O arm (1 radiation pneumonitis and 3 pancytopenia) and 2 in the V arm (2 radiation pneumonitis). So far 71% of patients have progressed and 72% have died. There was no difference in survival (median 16.3 vs 14.3 months, p=0.3) or progression-free survival (median 6.6 vs 5.7 months, p=0.2) between O and V arms. Conclusions: Vaccination with BEC2/BCG does not provide any survival advantage in limited disease SCLC patients after a major response to induction chemo-radiation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck & Co., Inc.
A single center's experience of phase I clinical trials: Characteristics of trials and patients.
Authors: B. Gaddapathi, G. K. Prithviraj, P. Fu, A. Dowlati
Journal: Journal of Clinical Oncology (2010)

e13110 Background: Our center has received 16 years of consecutive funding by the NCI for the conduct of early-phase clinical trials with phase I emphasis. We have also recently published the study and patient characteristics of 476 completed phase I clinical trials from other institutions encompassing 15,100 patients (Dowlati et al. J Clin Oncol 2008; Dowlati et al. Inv New Drugs 2009). Methods: The purpose of this analysis was to determine the characteristics of our phase I program (a program with NCI/CTEP emphasis) as related to study characteristics, i.e., sponsor, the number of participating sites, and accrual as well as patient characteristics, i.e., tumor types, race, performance status, and number of prior therapies. Results: We have completed 97 phase I trials from 1994 to 2009 enrolling over 1,200 patients. Forty-four percent were single- institutional studies. 37% were sponsored by NCI/CTEP; 26% were institutionally supported, and 38% were supported by pharmaceutical companies. Compared to published data, we perform a significantly higher number of institutionally supported phase I trials (26% vs. 4%, p < 0.0001). In addition, institutionally support trials have a higher degree of accrual (mean 20 pts) as compared to pharmaceutical-sponsored trials (mean 11 pts, p =0.001). This results from a higher frequency of multi-institutional studies with pharmaceutical sponsorship. Although we enroll a higher percentage of female patients compared to published data (50% vs. 44%), we have observed a significant decline in the number of female patients enrolling on phase I trials (p<0.0001), which coincides with a decline in the number of breast cancer patients participating (p=0.002). When comparing two time periods (period 1= 1994-2001; period 2= 2002-2009), in the first period 54% of patients were female as opposed to 47% in the second time period. There has been no change in other patient characteristics. Lung cancer patients comprise a smaller (∼4%) percentage of accruals in our series compared with published data (13%). Conclusions: Over 60% of phase I trials performed at our institution are either institutionally or NCI/CTEP supported. The characteristics of patients enrolled on these trials do not differ from other institutions. No significant financial relationships to disclose.
Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study
Authors: Francesco Ceppi, Sheila Weitzman, Wilhelm Woessmann, Kimberly Davies, Alvaro Lassaletta, Bettina Reismüller, Karin Mellgren, Anne Uyttebroeck, Iris Maia, Shaker Abdullah, Natasha Miakova, Darryl Glaser, Richard Cohn, Oussama Abla, Andishe Attarbaschi, Sarah Alexander
Journal: American Journal of Hematology (2016)

Central nervous system (CNS) involvement in patients with mature B non-Hodgkin lymphoma, post-transplantation proliferative disorder and acute lymphoblastic leukemia confers a significantly inferior prognosis as compared to patients without CNS disease. Intrathecal (IT) or intraventricular administration of rituximab is an option for this group of patients. We report 25 children with CNS involvement of CD20+ B lymphoid malignancies who received in total 163 IT/intraventricular rituximab doses. The median number of doses received by each patient was 6, with a median dose of 25 mg. The most common adverse events were Grades 1 and 2 peripheral neuropathies in five patients (20%), allergy in two patients, and headache in two patients. These events were self-limited, occurring in the 48 hours after treatment and resolving within 24 hr. Three patients presented with more severe though transient side effects, one with a Grade III neuropathy and two with seizure. Eighteen patients (72%) of those treated with IT/intraventricular rituximab, with or without other CNS directed treatment, achieved a CNS remission. This case series suggests that IT/intraventricular rituximab has therapeutic efficacy and relatively limited toxicity. Prospective trials of IT/intraventricular rituximab for patients with CNS involvement of CD20 + B lymphoid malignancies are warranted.
Combined simultaneous cisplatin/fluorouracil chemotherapy and split course radiation in head and neck cancer.
Authors: S G Taylor, A K Murthy, D D Caldarelli, J L Showel, K Kiel, K L Griem, B B Mittal, M Kies, J C Hutchinson, L D Holinger
Journal: Journal of Clinical Oncology (1989)

Fifty-three patients with stage III (eight patients, 15%), stage IV (36 patients, 68%), or recurrent disease (nine patients, 17%) entered a study of simultaneous cisplatin, 60 mg/m2 day 1, fluorouracil (5-FU) infusion, 800 mg/m2 days 1 to 5, and radiation, 2 Gy days 1 to 5, every other week for a total of seven cycles (70 Gy in 13 weeks). Patient acceptance was high, with only two patients (4%) refusing to complete therapy. The median actual dose delivered was 88% of the planned dose for cisplatin, 78% for 5-FU, and 70 Gy for radiation. Weight loss of 10% or more and severe mucositis were the most common side effects (53% and 48% incidence, respectively). All patients were followed at least 1 year (median, 51 months). While the complete response rate (55%) seemed no better than that reported in other series, freedom of progression of regional disease (73%), and the survival of all patients (median, 37 months) were substantially improved. Only 33% of partial responders have failed regionally, while 15% of complete responders have failed regionally (P greater than .10), which indicates that clinical assessment of response was unreliable. Stage, the presence of N3 disease, and delivery of less than the median actual dose received of 5-FU (but not cisplatin) were significantly associated with failure. This regimen is feasible and tolerable in this difficult patient population. It generally requires no special forced feeding techniques. Survival results from this limited institution study appear better than those using sequential multimodality therapies. With such favorable regional control, this approach may offer an alternative in the future to radical surgery and radiation in resectable disease. More definitive evaluation seems warranted.
Phase II trial of oral capecitabine (C) and weekly docetaxel (D) in patients with metastatic androgen independent prostate cancer (AIPC)
Authors: S. Marur, J. Eliason, L. Heilbrun, D. Smith, B. Dickow, R. Santucci, M. Cher, J. Forman, U. Vaishampayan
Journal: Journal of Clinical Oncology (2007)

5121 Background: Due to demonstrated synergistic anti-tumor effect of D and C related to docetaxel-mediated up-regulation of thymidine phosphorylase (TP), a phase II trial with weekly D and C in metastatic AIPC was performed. Endpoints of response and survival were correlated with biomarker levels of TP, dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) in tumor tissue and DPD in serum Methods: Patients with metastatic AIPC, with no prior chemotherapy for metastatic disease were eligible to receive D 36 mg/m 2 /week IV on days 1,8, and 15 and C 1,250 mg/m 2 /day in two divided doses on days 5–18. Cycles were repeated every 28 days and response was assessed every 2 cycles. Biomarker correlative study for Serum DPD and TP/DPD ratio and TS/DPD ratio on tissue were performed using mouse anti-TP, rat anti-DPD and mouse anti-TS monoclonal antibodies Results: 30 patients enrolled with median age of 69 years, median pretherapy PSA of 110 ng/ml (range 1.2 to 3716.9). 21(70%) had bone pain, Gleason score ≥ 8 in 18 (61%) patients; measurable disease progression in 9, bone scan progression in 18 patients and PSA only progression noted in 22 patients. 144 cycles have been administered (range 0–10 cycles). Grade 3 or 4 neutropenia seen in 3 patients and Grade 3 hand-foot syndrome in 2 patients. No treatment related deaths seen. PSA response (≥50% decline) noted in 22 (73.3%) with ≥90% PSA decline in 9 (30%) pts. Measurable disease PR noted in 5 of 9 patients (56 %). Median follow-up is 11 months (range 2.1 to 30.4). Median time to progression is 9.1 months (90% CI 6.2–15.1 months), and the median overall survival (OS) is 18.9 months (90% CI 14.9–26.4 months). 1 year PFS and OS is 44% and 84% respectively. Samples for DPD were available for 25 patients and pre-therapy tumor tissue for 23 patients. Quantitative fluorescence IHC has been performed on available samples, the final analysis is ongoing. Conclusions: The combination is well tolerated and demonstrates favorable and durable remission and survival outcomes. Correlation with biomarker analysis will be reported. This may help in selecting patients more likely to derive benefit from combination of D and C. Supported in part by Aventis Inc. No significant financial relationships to disclose.
Screen-and-treat colposcopy as public health strategy for cervical cancer early detection in high-risk population: The experience of the Centro de Estudios y Prevencion del Cancer (CEPREC) in indigenous population of Southern Mexico
Authors: S. Marcial-Toledo, J. Cortes-Guzman, L. Chavez, C. Guzman-Patraca, S. Terrazas-Espitia, J. Sanchez-Ruiz, J. Perez-Romero, R. Torres, M. Ramirez, F. Gutierrez-Delgado
Journal: Journal of Clinical Oncology (2006)

5012 Background: The incidence of cervical cancer in Mexico remains high, due to ineffective Papanicolau smear screening, social, educational, cultural and financial issues. Southern Mexico is a region with a high incidence of cervical cancer. CEPREC has designed educational, preventive and early cancer detection programs in that population (Onkologie 27:211). We propose screen-and-treat colposcopy for cervical cancer prevention as public health strategy in selected high-risk population. This study evaluates the feasibility and acceptability of this approach through an educational program. Methods: From 12/2002 to 12/2005, women living in Southern Mexico were educated about cervical cancer and its prevention and were offered colposcopy either in CEPREC facilities or in ambulatory clinics. Colposcopy diagnosis and cervical cytology were established according to the 1990 IFCPC criteria and the 2001 Bethesda System, respectively. A cone biopsy was indicated in patients diagnosed as having human papilloma virus (HPV), cervical intraepithelial neoplasia (CIN 1, CIN 2, CIN 3), or carcinoma. Patients diagnosed as having HPV, CIN 2 and CIN 3 were treated by large loop excision of the transformation zone under local anesthesia. Results: 8281 women (median age 39 years, range: 14–87) were evaluated. 5645 (68%) of them underwent colposcopy in ambulatory clinics. 1171 (14%) women were illiterates and the highest education level was 9 years in 4881 (59%). Median age at first intercourse and first Papanicolau smear were 19 and 29 years, respectively. 4251 (51%) women had vaginal symptoms before colposcopy. Abnormal colposcopy (HPV, CIN 1, CIN 2 or CIN 3), was diagnosed in 1073 (13%) patients and 9 (&lt;1%) had carcinoma. 238 (22%) of them were treated on site. Low-Grade (n = 190) (80%), and high-grade squamous intraepithelial lesions (n = 48) (20%), were diagnosed in those patients. Conclusions: Screen-and-treat colposcopy is a feasible public health strategy with high acceptability in selected high-risk population and could be an alternative to cytology-based screening programs. No significant financial relationships to disclose.