tbuckley/cabot-search huggingface dataset:
Pentostatin, cyclophosphamide and rituximab is an active regimen with low toxicity for previously treated patients with B-cell chronic lymphocytic leukemia and Waldenström's macroglobulinemia
Authors: M. Hensel, F. Krasniqi, M. Villalobos, M. Kornacker, A. D. Ho
Journal: Journal of Clinical Oncology (2004)

6557 Background: Pentostatin has demonstrated significant activity as a single agent in pts with low-grade B- and T-cell lymphomas including CLL, and is less myelosuppressive than other purine analogs. High remission rates have been reported with the combination of purine analogs, alkylating agents and rituximab, even in heavily pretreated pts with CLL. We have conducted a phase II trial in pts with CLL and WM. PC was followed by a maintenance therapy with rituximab for those pts with WM achieving complete or partial remission after PC. Methods: 29 pts with CLL (n=18) and WM (n=11) have been enrolled to date, 22 of whom are evaluable for tumor response and toxicity. All pts received pentostatin 4 mg/m(2) and cyclophosphamide 600 mg/m(2), administered on day 1 of each cycle, and cycles were repeated every 3 weeks for six treatments. The median number of prior treatment regimens was 3 (range, 0 to 8) including 12 pts (41%) refractory to or relapsed within 1 year after prior fludarabine therapy. Pts with WM who achieved a remission after PC chemotherapy, were subsequently treated with rituximab 375mg/m(2), starting 1 month (mo) after the last cycle of PC, repeated every 3 months. Results: An objective tumor response after PC was confirmed in 14 out of 22 evaluable pts (63%), with 1 CR and 13 PR. Toxicity was mild, with only infections WHO grade 2–3 and nausea/vomiting grade 2. 1 of 8 pts with WM achieved a CR, 5 a PR, after a median of 3 cycles of PC (range, 2–6). 6 of them were subsequently treated with rituximab every 3 mo, for a median of 5 infusions thus far (range, 2 to 9). None of them has relapsed to date with stable IgM serum levels. In 2 pts with PR after PC, remission status has further improved due to rituximab, with normalisation of IgM levels. Conclusions: Our data indicate that PC is safe and effective in previously treated patients with CLL and WM. Hematologic toxicity is less as compared to other combinations of purine analogs and cyclophosphamide. Maintenance therapy of WM with rituximab as single infusion every 3 mo can be administered safely and may convert pts with PR to CR. No significant financial relationships to disclose.
Management of bone metastases from lung cancer: Consensus recommendations from an international panel
Authors: K. Nackaerts, P. G. Harper, C. Manegold, D. S. Ettinger, P. Kosmidis, C. J. Langer
Journal: Journal of Clinical Oncology (2008)

19080 Background: In approximately 30% to 40% of patients with advanced lung cancer (LC), bone metastases (mets) develop that undermine the structural integrity of the affected bone. With therapeutic advances, patients are now living long enough for the effects of tumor on bone to manifest in potentially debilitating skeletal-related events (SREs) including pathologic fracture, spinal cord compression, the requirement for surgery or palliative radiotherapy to bone, and hypercalcemia of malignancy. Currently, guidelines for the detection and treatment of bone mets in patients with LC are limited, possibly because of insufficient prospective data. However, this gap in patient management protocols can be bridged by retrospective and subset analyses of trial data and the collective experience of LC specialists. Methods: Current guidelines for the management of patients with advanced LC were reviewed by an international panel of experts, and consensus recommendations for the diagnosis and treatment of bone mets from LC were suggested based on literature reports and the collective clinical experience of the panel. Results: Patients with resectable tumors should be screened for bone mets at initial diagnosis and staging, preferably by whole-body positron emission tomography (PET scan), if available. In patients with bone mets, with or without symptoms, current data support the initiation of zoledronic acid (4 mg via 15-minute infusion every 3 to 4 weeks) and continuation of therapy per label as long as it is well tolerated in patients with an ECOG performance status ≤ 2. Initiation of zoledronic acid should also be considered in patients with compromised performance status primarily because of symptoms of bone mets. Conclusions: Early screening for bone mets in patients with LC and use of zoledronic acid to prevent SREs in patients with bone mets and ECOG performance status ≤ 2 are recommended. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Oncology Novartis Oncology
Novel Murine Model To Study Modulation of Genes and Molecular Pathways Induced Following In Vivo Interaction between Multiple Myeloma Cells and Human BM Milieu.
Authors: Paola Neri, Pierfrancesco Tassone, Masood Shammas, Mariateresa Fulciniti, Yu-Tzu Tai, Simona Blotta, Rao Prabhala, Mariateresa Di Martino, Laurence Catley, Pierosandro Tagliaferri, Salvatore Venuta, Ruben Carrasco, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2006)
An ambispective observational study in the safety and efficacy of abiraterone acetate in the French temporary authorizations for use (ATU): Predictive parameters of response.
Authors: David Azria, Christophe Massard, Diego Tosi, Nadine Houede, Florence Joly, Gwenaelle Gravis, Remy Delva, Sylvestre Le Moulec, Igor Latorzeff, Jean-Marc Ferrero, Stephane Culine, Sylvain Ladoire, Sophie Tartas, Stephane Oudard, Jean-Michel Pierre Rodier, Brigitte Laguerre, Jerome Alexandre, Delphine Topart, Philippe Beuzeboc
Journal: Journal of Clinical Oncology (2012)

149 Background: The Temporary Authorizations for Use (ATU) procedure is an exceptional measure making available medicinal products that have not yet been granted a Marketing Authorisation. Abiraterone acetate (AA) was available for ATU since December 2010 in France. We then decided to evaluate the tolerance and efficacy of this treatment and identify predictive factors of response. Methods: 82 centers were contacted and clinical data were reported in two months (15 th July-19 th September 2011). Patients were defined as non-responders in case of interruption of AA due to disease progression or death. PSA values were recorded at each medical visit. Reported toxicities were also recorded. Statistical analyses were descriptive and predictive factors were determined. Results: A total of 18 centers accepted to participate in this study including 381 patients. Median age at diagnosis was 63 years. The Gleason score (n=320) were 4-6, 7, and 8-10 in 13.4%, 36.9% and 49.7%, respectively. Before AA, the type of metastasis was bone only, organs only, and bone+organs in 45.4%, 7.9% and 46.7%, respectively. Median PSA before CT and before AA was 58.1 and 137.5 ng/ml, respectively. Median duration of hormonotherapy (HT) before any CT was 34 months. Median duration of CT before AA was 6.1 months with a median number of CT lines of one. Median duration of AA was 117 days. In the non-responders group (n=114), median duration of AA was significantly shorter than in the responders group (n=267), 87 days vs 147 days, respectively (p&lt;0.0001). One third of the patients in the responders group presented a PSA increase over time but continued AA as they clinically improved. Only 13 patients stopped AA for grade 3-4 toxicities. GIeason 8-10 and the number of CT lines (&gt;1) before AA were identified as independent predictive factors of non response. Conclusions: This report is the largest ambispective observational study of AA in an ATU process. PSA values during AA treatment were used as a good indicator of progression. GIeason 8-10 and the number of CT lines (&gt;1) before AA were identified as independent predictive factors and therefore could be used for further strategies in this setting.
Interobserver agreement of lung adenocarcinoma diagnosis when applying the 2011 Iaslc/ats/ers Multidisciplinary Classification of Lung Adenocarcinoma
Authors: E. E. Duhig, B. E. Clarke, D. Godbolt, A. Dettrick, J. Pauli, I. A. Yang, R. Bowman, K. M. Fong
Journal: Journal of Thoracic Oncology (2012)
Factors affecting disease free survival in Iranian patients with invasive ductal carcinoma of the breast
Authors: M. Mokri, J. Raafat, S. Shariat Torbaghan, M. Karbassian, M. Shakiba, M. Atri
Journal: Journal of Clinical Oncology (2008)

22130 Background: Factors affecting Disease Free Survival (DFS) in breast cancer are very important in treatment planning and determining the prognosis of the patients. In this study, we have assessed the important factors affecting DFS of a large group in Iranian patients with invasive ductal carcinoma (IDC). Methods: The data on demographic, clinical, histopathological (including grade and stage) and biomarkers (including estrogen receptor[ER], progesterone receptor [PR], Her-2, p53, ki-67 and Cothepsin-d) in 1823 Iranian patients with surgically candidated (Modified Radical Mastectomy or Conservative breast surgery) IDC were collected. All patients referred to Day General Hospital and the diagnosis of IDC was proved by histopathologic assessment. After surgery, all patients were followed up according to routine schedule and if they encounter a clinical problem, they referred and underwent routine plans for evaluation of metastasis. Time from surgery to the last visit recorded and if any metastasis was detected, the time between surgery and detection considered as DFS. Results: Totally 1823 patients entered the study. The mean age was 48.8±10.9 years old (20–85) and 1091(59.8%) were equal or under 50 years old. The ER, PR, Her-2 and p53 were positive in 68.5%, 64.5%, 40.1% and 40.5% of patients respectively. 29% were stage III or IV, 26.6% were in N2 or N3 and 85.1% had 2 or 3 Bloom-Richardson histological grade. 37.1% showed blood vessel involvement in pathology. In a Kaplan-Meyer analysis, the mean DFS of patients was 102.9±1.8 month (95% confidence interval [CI]=99.2–106.16 months). In a multivariate Cox regression model for DFS, the age (hazard ratio=0.98[95% CI=0.97–0.99]), tumor stage (hazard ratio=1.85[95% CI=1.15–2.99], vascular invasion (hazard ratio=1.43[95% CI=1.02–2]) and involved lymph nodes (hazard ratio=1.05[95% CI=1.02–1.08]) were statistically significant. (All P-Values<0.04). The tumor grade and negativity of both ER and PR were not statistically significant in the model. (Both P-Values >0.14). Conclusions: The lower age, higher tumor stage, vascular invasion and higher involved lymph nodes are associated with lower DFS. No significant financial relationships to disclose.
Association between bisphosphonate use in metastatic breast cancer (MBC) and overall survival.
Authors: A. Mathew, M. Q. Rosenzweig, A. Brufsky
Journal: Journal of Clinical Oncology (2011)

102 Background: Preclinical studies on bisphosphonates in breast cancer have suggested an anti-tumor effect in addition to its bone protective role. However, randomized controlled trials of bisphosphonates versus placebo have found little evidence of increased overall survival (OS) in MBC. We conducted a retrospective single-institution cohort study of MBC patients to evaluate the association between bisphosphonate use and overall survival. Methods: Baseline demographic and tumor specific data were collected on newly diagnosed MBC patients between January 1998 and December 2009. Other variables included the number and sites of each metastasis, use of baseline neoadjuvant and adjuvant chemotherapy, and use of hormone therapy. Bisphosphonate use was defined as present if it was administered for a period of at least 3 months in the metastatic setting. Overall survival was determined from the date of diagnosis of first metastatic disease. Survival analysis was performed using the Kaplan-Meier method and Cox proportional-hazards model. Results: Data were available on 737 patients with MBC, of whom 434 died during a median follow-up of 2 years; median age was 50.3 years. 92% of patients were Caucasian; 32% were both ER and PR-negative; and 31% were HER2-positive. Over 67% of MBC patients had bone metastasis and nearly 80% received bisphosphonates. Multivariate analysis found an overall survival benefit for bisphosphonate use, with a hazard ratio of 0.63 (95% confidence interval: 0.48-0.84; p&lt;0.002), when adjusted for variables with significant effect on survival on univariate analysis and other known prognostic variables. These variables include age, stage at diagnosis, race, hormone receptor status, HER2 status, and number of metastatic sites, presence of bone metastasis and the use of adjuvant therapy. The administration of adjuvant therapy did not yield a significant survival advantage in the analyses. Conclusions: This retrospective cohort study provides evidence for an OS benefit with the use of bisphosphonates in MBC even after controlling for other significant prognostic factors.
Clinical and immunologic response of patients with advanced solid tumors vaccinated with an optimized cryptic hTERT peptide (Vx-001)
Authors: A. Kotsakis, K. Vetsika, N. Christou, M. Drogaris, N. Pantazopoulos, D. Aggouraki, G. Konsolakis, K. Kosmatopoulos, D. Mavroudis, V. Georgoulias
Journal: Journal of Clinical Oncology (2008)

3030 Background: The clinical and immunologic efficacy of the optimized peptide TERT572Y (Vx-001) presented by HLA- A*0201 in patients with advanced malignancies was investigated. Methods: In the context of an expanded phase I-II study, 71 patients with advanced solid tumors (breast cancer n=10; NSCLC n=11; prostate cancer n=10; mCRC n=2; RCC n=6; pancreatic cancer/cholangiocarcinoma n=14; melanoma n=8; HCC n=3; others n=7) who had been previously treated with standard chemotherapy (disease status at enrollment: stable disease n=21 and progressive disease n=50) received two subcutaneous injections of 2 mg of the optimized TERT572Y peptide followed by four injections of 2 mg of the native TERT572 peptide given every three weeks. The peptide-specific immune responses were assessed by interferon-γ Elispot at baseline, before the 3rd (early response) and after the 6th (late response) vaccination. Clinical outcome was evaluated after the 6th vaccination (based on RECIST criteria) and every three months thereafter for patients who did not progress. Results: Thirty-seven (52%) out of 71 patients completed the vaccination program. The main toxicity was grade 1 local skin reactions. An early and late immunologic response was detected in 29 of 56 (51.8%) and 25 of 30 (83%) evaluable patients, respectively. There were three (4.2%) objective clinical responses (HCC n=1; NSCLC n=2) and 22 (31%) disease stabilizations. All disease stabilizations occurred in early immunologically responding patients. Among the patients with PD before vaccination the median overall survival was 23.5 versus 7 months (p=0.056) in early immune responders versus non-responders, respectively, and was significantly higher in patients with late immunologic response (not reached) than in non-responding patients (9.5 months) (p=0.007). Conclusions: Vx-001 is a strongly immunogenic vaccine capable of inducing clinical responses in immunologically responding patients with progressive advanced solid tumors. Detailed and updated results will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Vaxon Biotech
Surveillance for stage I testicular seminoma: Retrospective analysis of prognostic factors for relapse at a single institution in Japan
Authors: K. Kakimoto, Y. Ono, N. Meguro, A. Kawashima, T. Kinouchi, M. Usami
Journal: Journal of Clinical Oncology (2007)

15630 Background: Treatment options for clinical stage I seminoma include adjuvant radiotherapy (RT) as well as surveillance and adjuvant chemotherapy. Although adjuvant RT remains the treatment of choice in most centers, the success of surveillance of patients with stage I nonseminomatous germ cell tumors and the establishment of curative chemotherapy for advanced disease have led to re-examination of the standard treatment approach. Data available from the surveillance and adjuvant RT series suggest that nearly 100% of patients with stage I testicular seminoma are cured, whichever approach is chosen. We report here results of a retrospective analysis of prognostic factors for stage I testicular seminoma. Methods: Between January 1980 and December 2004, surveillance was performed for 61 patients. Tumor characteristics (age at diagnosis, size, elevation of beta hCG level, invasion of the rete testis, vascular invasion, and lymphatic invasion) were examined as factors possibly predictive of relapse. Cause-specific survival rate was calculated using the Kaplan-Meier method. Results: With a median follow-up of 10.5 years (range, 2.35–20.8 years), 7 relapses were observed, with an actuarial 5- year relapse-free rate (RFR) of 89.2%. On univariate analysis, only tumor size (RFR: &lt;8cm, 96%; =8cm, 76%; p=0.029) was predictive of relapse. Age at diagnosis (RFR: &lt;36, 89%; =36, 91%), elevation of beta hCG level (RFR: 93% [normal] v 91% [elevated]), invasion of the rete testis (RFR:92% [absent] v 90% [present]), vascular invasion (RFR:89% [absent] v 86% [present]), and lymphatic invasion (RFR: 89% [absent] v 78% [present]) were not predictive of relapse. The overall relapse rate was 11.5%. Overall 5-year survival rate was 97%. Conclusions: Size of primary tumor was found to be predictive of relapse in patients with stage I seminoma managed with surveillance, on analysis at a single institution in Japan. No significant financial relationships to disclose.
Algorithm of monitoring of patients with family history of cancer as a method of cancer prevention
Authors: V. D. Petrova, T. V. Sinkina, N. A. Zarubina, S. A. Terekhova, J. N. Dimitriadi, I. A. Selezneva, A. F. Lazarev
Journal: Journal of Clinical Oncology (2007)

1542 Background: Existent genetic tests are not able to provide effective forecasting of all cancer sites and all those methods are generally expensive. At the same time approximately 50% of population has cancer susceptibility and 10% - hereditary cancer syndromes. The purpose of this study was to develop the algorithm of monitoring to provide effective forecasting and prevention of cancer in patients with hereditary cancer susceptibility. Methods: The algorithm of monitoring of patients with family history of cancer includes 2 stage: I - diagnostic, II - treatment and rehabilitation. In the I stage patients with 3 and more relatives by blood who had cancers of any site are revealed by oncologist. Their genealogical trees are analyzed by geneticist. All those patients are registered in the registry of “cancer”-families’ members, interviewed and got all the necessary diagnostic procedures with the following multivariative analysis (of more than 200 geno- and phenotypic characteristics). Patients with determined high risk of malignancies undergo deep clinical and instrumental examination, site-by-site searching for cancer, molecular genetic tests. In the II stage individual recommendations for the patients are developed, pretumour lesions are treated, preventative surgery is performed (resection of a target organ) and the measures for strengthening of anti-tumour resistance are taken. All the patients of the registry get the periodic health examination for term of life: preventive examination once per 6 months, multivariative analysis once per 3 years. Results: The registry of “cancer”-families’ members included 421 families - 1833 patients (232 men and 1601 women at the age of 28–74). In 2003–2006 there were revealed obligatory pre-cancer lesions in 637 patients, cancers in situ - in 45 patients, and cancers of different sites - in 69 patients (in I stage - 78.3%, II stage - 18.9%, III stage - 2.8%, IV stage - 0). Conclusions: This algorithm of monitoring of the patients from the registry of “cancer”-families’ members made it possible to provide high effectiveness of cancer prevention and early detection. No significant financial relationships to disclose.
Phase I-II study of a Farnesyl Transferase Inhibitor (FTI), SCH66336, in patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML).
Authors: C Ravoet, P. Mineur, V. Robin, L. Debusscher, André Bosly, Marc André, H. El Housni, A Soree, P. Martiat
Journal: Blood (2002)
Triplet therapy with oxaliplatin, irinotecan and escalating doses of capecitabine in liver metastases from colorectal cancer patients
Authors: M. Ponz-Sarvisé, R. Zarate, J. Rodriguez, A. Viudez, A. Chopitea, E. Bandres, A. Hernandez, I. Gil-Bazo, C. Olier- Garate, J. Garcia-Foncillas
Journal: Journal of Clinical Oncology (2008)

15020 Background: The combination of oxaliplatin, irinotecan and 5-fluorouracile has shown encouraging results in metastasic CRC patients. The aim of this study was to determine the maximum-tolerated dose (MTD) and to evaluate the efficacy and tolerability of capecitabine in combination with irinotecan and oxaliplatin in chemo naive colorectal cancer patients with liver metastases. Methods: 24 patients with liver metastases from colorectal cancer were treated with a biweekly schedule of Oxaliplatin 85 mg/m2 on day 1, Irinotecan 150 mg/m2 on day 1 and escalating doses of capecitabine (level 1: 850 mg/m2, 2: 1000 mg/m2 and 3: 1250 mg/m2) on day 1–7 of each cycle. Results: 23 patients (14M/9F, median age: 57, median ECOG: 1) were included. The median number of cycles administered was 7. No dose limiting toxicity (DLT) was observed in level 1. In level 2 grade 4 neutropenia was noted in one pt. Subsequently 3 more patients were included in this cohort with no additional toxicity. DLT ocurred in two out of three pts at the 1250 mg/m2 level dose and consisted of grade 3 diarrhea and grade 4 neutropenia respectively. 11 aditional pts were recruited in dose level 2 with no further DLTs seen. Overall, main grade 3–4 toxicities were anemia (1.4%), asthenia (4.2%), leucopenia (1.4%), neutropenia (8.4%), vomiting (2.8%), diarrhea (4.2%) and neurotoxicity (grade 2 8.3% and grade 3 1.4%). Preliminary evidence of activity has been noted, with 15 pts achieving major radiological responses. Conclusions: Dose limiting toxicity of this triplet combination is neutropenia and diarrhea. Recomended capecitabine dose for phase II trials is 1000 mg/m2 on days 1–7 every two weeks. Preliminary evidence of activity warrants further investigation No significant financial relationships to disclose.