tbuckley/cabot-search huggingface dataset:
Phase II safety and efficacy study of CT-011, a humanized anti-PD-1 monoclonal antibody, in combination with rituximab in patients with relapsed follicular lymphoma.
Authors: J. R. Westin, F. Chu, M. Foglietta, R. Rotem-Yehudar, S. S. Neelapu
Journal: Journal of Clinical Oncology (2010)

TPS305 Background: Follicular lymphoma (FL) is one of the most immune-responsive of all cancers. However, immunosuppressive mechanisms in the tumor microenvironment may impair the efficacy of antitumor immune responses. We have recently identified the programmed death (PD)- 1/PD-ligand pathway as an important immunosuppressive mechanism in the FL tumor microenvironment. Expression of the coinhibitory PD-1 receptor was markedly increased on intratumoral T cells and associated with decreased reactivity to autologous FL tumor cells. Blocking PD-1/PD-ligand pathway with CT-011 enhanced the proliferation of antitumor T cells and augmented the expression of activating receptors on human NK cells. Administration of CT-011 delayed tumor growth and improved survival of mice in lymphoma xenograft models and combination with rituximab further improved survival compared with rituximab alone (Chu et al, Blood, Nov 2009; 114: 724.). In a phase I clinical trial, CT-011 was safe, induced sustained elevations of CD4+ T cells, and the sole patient with FL on the trial, who had large tumor masses, achieved a durable complete remission lasting >14 months (Berger et al, Clin Cancer Res, 2008). Based on these data, we are now conducting a single-arm phase II trial with CT-011 and rituximab in relapsed FL patients (n = 30). The rationale is that the combination is likely to activate both innate (NK cells) and adaptive (T cells) arms of the immune system and thereby enhance the clinical efficacy without increasing toxicity. The primary endpoint is overall response rate. Methods: Patients with FL, relapsing after at least 1 but not more than 4 prior therapies, with rituximab-sensitive disease will be eligible. Patients must be ≥ 18 years, have measurable disease, adequate organ function, and absolute lymphocyte count of ≥ 0.6×109/L. Patients with HIV, hepatitis B or C, and autoimmune diseases are excluded. CT-011 will be administered IV every 4 weeks for 4 infusions and rituximab will be administered IV weekly for 4 weeks. The trial was activated in January 2010 and one patient has been enrolled. Blood and tumor samples will be collected to assess the effect of CT-011 on T cells and NK cells. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CureTech
Effect of a combination of tyrosine kinase inhibitor imatinib with doxorubicin shows in breast cancer cell lines.
Authors: L. Dahmke, M. T. Weigel, M. Bauer, C. Schem, I. Alkatout, W. Jonat, C. Mundhenke
Journal: Journal of Clinical Oncology (2010)

e13657 Background: In the need to optimize breast cancer therapies, constantly new targeted agents are examined for their potential clinical use. In a broad range of solid and haematological cancers tyrosine kinase inhibitors, which target growth factor receptors like PDGFR α and β as well as c-kit, have already shown to be of clinical benefit with tolerable side effects. Here effects of the tyrosine kinase inhibitor imatinib as a single agent and in combination with standard chemotherapy (doxorubicin) have been investigated in vitro. Methods: Biological effects of imatinib in breast cancer cell lines MDAMB 231 and MCF 7 were tested using proliferation assays, TUNEL assays and migration assays. Cells were incubated with different concentrations of doxorubicin (0,25 nmol-500μmol) and imatinib (1-15 μmol) each as single agent and in combination. Results: Incubation with imatinib as a single agent reduces cell proliferation in a dose-dependent manner with an IC 50 of 6uM for both breast cancer cell lines. Moreover, imatinib induces apoptosis and reduces cell migration. Combining imatinib with doxorubicin leads to an additive effect on cell growth inhibition in MDA MB 231 and MCF 7 cells. A further reduction in cell migration can be detected when imatinib is combined with doxorubicin. In the hormone receptor positive cell line MCF 7, a significant increase in apoptotic cells can be detected when combining both drugs compared to each single treatment. The concentrations of doxorubicin as well as the imatinib concentrations can be applied in clinical use. Conclusions: Combining imatinib with doxorubicin shows a significant improvement in inhibiting breast cancer cell proliferation and migration, as well as apoptosis induction. These data suggest that the combination of standard chemotherapy with imatinib could be beneficial for breast cancer patients. No significant financial relationships to disclose.
Autologous bone marrow transplantation for pediatric Hodgkin's disease: a case-matched comparison with adult patients by the European Bone Marrow Transplant Group Lymphoma Registry.
Authors: C D Williams, A H Goldstone, R Pearce, S Green, J O Armitage, A Carella, G Meloni
Journal: Journal of Clinical Oncology (1993)

PURPOSE We analyzed the outcome of autologous bone marrow transplantation (ABMT) in pediatric and adult patients with Hodgkin's disease (HD) by means of a case-controlled study. PATIENTS AND METHODS Eighty-one pediatric HD patients who had undergone ABMT and who had been reported to the European Bone Marrow Transplant Group (EBMTG) Lymphoma Registry were compared with a case-matched group of 81 adult patients who had undergone the same procedure. The case-matching was performed following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. RESULTS The PFS rate was not significantly different between the groups (39% for the pediatric group v 48% for the adult group). The overall relapse/progression rates for the groups were 52% and 40%, respectively. This was not a statistically significant difference and the sites of relapse were similar. There was no significant difference in the incidence or causes of procedure-related morbidity or mortality of the two groups. CONCLUSION This study suggests that patients with pediatric HD have the same outcome at ABMT as their adult counterparts; however, long-term complications will need to be carefully monitored.
Factors associated with concerns about recurrence in women with breast cancer
Authors: K. Corbin, C. G. Shields, M. Weiss, J. J. Griggs, D. R. Lambert
Journal: Journal of Clinical Oncology (2007)

593 Background: The purpose of this study was to examine factors associated with concerns about disease recurrence in women with ductal carcinoma in situ (DCIS) and invasive breast cancer. Methods: Participants completed an anonymous survey instrument through the website of www.breastcancer.org , a non-profit organization. Participants provided information on diagnosis and treatment characteristics, demographics, preferences for treatment, fears of recurrence as measured by the Concerns of Recurrence Scale (Vickberg, Ann Behav Med 2003), and completed the SF-36 Mental Health Subscale. Participants were also asked if they had been told they had a “good cancer,” “good kind of cancer,” or “better cancer than others.” Bivariate and multivariate analyses examined the relationships between fears of recurrence and mental health, patient, disease, and treatment factors. Results: 331 women completed the survey instrument, 125 with DCIS and 206 with invasive breast cancer. In multivariate analysis, fear of recurrence was associated with age (β= -.24, 95% CI -.44,-.06), time since diagnosis (β= -.09, 95% CI -.16,-.02), having a mastectomy (β= -45, 95% -.83,-.08), and a diagnosis of DCIS (β= -1.00, 95% CI - 1.48,-.53). Women with DCIS who were told they had a “good cancer” had greater fear of recurrence than women with DCIS who were not told they had a good cancer (β= 1.25, 95% CI .56, 1.93). No such association in women with invasive breast cancer was found. Mental health was negatively correlated with fear of recurrence in women with DCIS (β= -0.43, 95% CI -.61,-.25). Level of education and satisfaction with the relationship with physicians were not associated with fear of recurrence. Conclusions: Older age and time since diagnosis are associated with reduced fears of recurrence. Women who have had a mastectomy also have lower fears of recurrence. Interestingly, receiving a message that one has a “good cancer” appears to be associated with increased fear of recurrence although the direction of the association cannot be determined from this study. Further research into effective and appropriate methods of informing and reassuring patients with different prognostic profiles of breast cancer is warranted. No significant financial relationships to disclose.
A Prospective Phase II Study on Tandem Autografting-Nonmyeloablative Allografting for Newly Diagnosed Myeloma: Final Results of the Gruppo Italiano Trapianto Midollo Osseo.
Authors: B. Bruno, M. Rotta, F. Patriarca, D. Mattei, B. Allione, F. Carnevale-Schianca, A. Rambaldi, M. Casini, V. Montefusco, M. Parma, P. Bavaro, F. Onida, A. Busca, L. Castagna, M.P. Iori, D. Maloney, B. Sandmaier, F. Benedetti, N. Mordini, L. Giaccone, R. Sorasio, F. Fiore, A. Filippi, A. Palumbo, M. Aglietta, A. Levis, R. Foà, P. Di Bartolomeo, E. Pogliani, G. Lambertenghi-Deliliers, M. Falda, M. Petrini, P. Corradini, R. Fanin, U. Ricardi, R. Storb, I. Baldi, Mario Boccadoro
Journal: Blood (2007)
High plasma levels of fenretinide (4-HPR) were associated with improved outcome in a phase II study of recurrent ovarian cancer: A study by the California Cancer Consortium
Authors: C. P. Reynolds, T. Frgala, D. D. Tsao-Wei, S. Groshen, R. Morgan, M. McNamara, S. Scudder, J. A. Zwiebel, H. J. Lenz, A. A. Garcia
Journal: Journal of Clinical Oncology (2007)

5555 Background: 4-HPR is a synthetic retinoid with dose-dependent cytotoxicity in vitro for ovarian cancer cell lines, especially at concentrations &gt; 10 μM. We previously reported preliminary results of a phase II trial (Garcia et al, Proc ASCO 2004: a5056) that showed encouraging stabilization of disease. Methods: 4-HPR capsules were given orally (900 mg/m 2 /bid for 7 days every 21-days) to women with recurrent ovarian cancer. Steady-state plasma concentrations of 4-HPR were determined by HPLC. Patients were required to have uni-dimensionally measurable disease, 0–2 chemotherapy regimens for recurrent disease, and performance status 0–2. The primary endpoint was response rate by RECIST criteria; secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: 31 patients were enrolled to the first stage; 28 patients were evaluable for response, with a median of 3 prior chemotherapy regimens (range: 1–3); 24 patients were evaluable for pharmacokinetics. A total of 172 4-HPR treatment cycles were given. Eleven patients experienced at least one grade 3 toxicity and one patient had grade 4 fatigue. No objective responses were observed, leading to study closure. Best response was stable disease in 13 patients (42%) with a median duration of 7.9 months (2.1–25.8 months). 4-HPR steady-state plasma levels ranged from 3.1–12.5 μM. PFS at 6 months was 26% (± 0.08 SE), 42 % (± 0.14 SE) for patients with 4-HPR plasma levels = 9 μM (n=12), and 17% (± 0.11 SE) for plasma levels &lt; 9 μM (n=12). OS with plasma levels = 9 μM was significantly higher than for those with 4-HPR levels &lt; 9 μM (66% vs. 13% at 18 months, adjusted p-value = 0.016). Conclusions: 4-HPR may provide clinical benefit to patients with recurrent ovarian cancer who obtain high 4-HPR plasma levels. Trials in ovarian cancer of 4-HPR focused on progression-free survival as an endpoint are justified using formulations with improved bioavailability. Supported by N01-CM-62209. No significant financial relationships to disclose.
Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Comparison of infusional FU/oxaliplatin(OX)+BV and oral FU/OX+BV.
Authors: Kazuteru Hatanaka, Satoshi Yuki, Hiroshi Nakatsumi, Hiraku Fukushima, Hirohito Naruse, Takashi Kato, Takashi Meguro, Michio Nakamura, Ichiro Iwanaga, Minoru Uebayashi, Miki Tateyama, Kazunori Eto, Mineo Kudo, Sosuke Kato, Hiroyuki Okuda, Susumu Sogabe, Kencho Miyashita, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2015)

527 Background: A few reports have shown no difference between the efficacy of infusional FU and that of oral FU (Capecitabine/S-1) for colorectal cancer, and some studies have reported the non-inferiority between infusional FU/Oxaliplatin (OX) and oral FU/OX for metastatic colorectal cancer (mCRC). We performed a sub-group comparison between infusional FU/OX (mFOLFOX6 + BV: iFU) and oral FU/OX (CapeOX/SOX + BV: oFU) from the HGCSG0802 observational cohort study with investigated Japanese patients (pts) treated with first line BV for mCRC. Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), time to treatment-failure (TTF), response rate (RR), safety and so on. The key eligibility criteria of HGCSG0802 were with evaluable lesions, older than 20 years, ECOG PS 0-2, and this analysis used the cohort treated with OX-based regimens.In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. PFS and TTF were compared using log-rank test. Results: Of 108 pts (the full analysis set), 95 pts were evaluable for treated with OX-based regimens. Forty-eight pts (50.5%) were treated with iFU and 47 pts (49.5%) were treated with oFU (CapeOX + BV 42 pts/SOX + BV 5 pts). The pts characteristics between those were generally balanced except for PS 0-1 (72.9% in iFU/93.6% in oFU; p=0.012) and synchronous liver metastases (mets) (93.8% in iFU/78.8% in oFU; p=0.040). Adverse events ≥grade 3 were balanced except for leucopenia (25.0% in iFU versus 2.1% in oFU; p=0.002) and neutropenia (43.5% in iFU and 10.9% in oFU; p=0.001). Hand-foot skin reaction was not different between two cohorts. RR was 62.5% in iFU versus 71.1% in oFU (p=0.835). The median PFS was 8.3 months in iFU versus 8.2 months in oFU (p=0.835). Conclusions: The HGCSG0802 could be a database to investigate first line BV for mCRC in clinical practice. As a result of this analysis, in Japanese daily practice, efficacy was no significant difference between infusional FU/OX and oral FU/OX, and the profiles of adverse events varied from each regimens.
Treatment and clinical outcome of young (age 40 and younger) patients with advanced non-small cell lung (NSCLC).
Authors: O. Caffo, A. Ceribelli, S. Ricciardi, V. Murgia, A. Bearz, F. Grossi, F. Rosetti, F. De Marinis, E. Galligioni
Journal: Journal of Clinical Oncology (2010)

e18117 Background: NSCLC is a very uncommon in pts ≤ 40 years and is usually considered as a distinct disease, with a better prognosis compared to older pts. In recent years, third generation drugs and targeted therapies have improved survival in pts with IIIB/IV stage, achieving a 10-12 mos median survival (MS). Some studies have reported small series of young pts with NSCLC but the age cut-offs varied among studies and most of them did not address the clinical outcomes of the IIIB/IV group. The present report specifically addresses the treatment and the clinical outcomes of pts ≤ 40 years with IIIB/IV stage NSCLC treated after 2000. Methods: We reviewed all pts referred for NSCLC from 2000 to 2009 to our institutions and have selected a consecutive series of 64 pts ≤ 40 years. Twelve pts with early stage were excluded and 52 with IIIB/IV NSCLC entered this study. Pts characteristics: male/female 48%/52%; median age 37 years (range 26-40); stage IIIB/IV 4%/96%; histological type: adenocarcinoma 77%, squamous 8%, other 15%. In IV stage pts, 45 had synchronous metastases, 4 developed distant metastases after radical surgery, and the last after radiochemotherapy for locally advanced NSCLC. Metastatic sites of these pts were lung in 52%, liver in 16%, lymph nodes in 38%, brain in 24%, bone in 26%, pleural in 18%, and adrenal in 6%. Results: All but one pts (who died before therapy), received systemic treatment for their IIIB/IV disease: 37% received only one line, 33% two lines, 22% three lines, and 8% four lines. Forty-five pts received as first-line a platinum-based doublet (among them 32 were treated with cisplatin + gemcitabine and 4 received bevacizumab too), 2 a platinum-based triplet, 4 a single-agent therapy. The response rate was 33% (2 CR + 15 PR). Thirty-two pts received a second-line treatment (21 received chemotherapy. 11 TKi), 15 a third-line (10 chemotherapy, 5 TKi) and 4 a fourth-line chemotherapy. The MS is 16 mos with a 58.5% 1-y OS. Conclusions: In our experience, ≤ 40 years pts with IIIB/IV NSCLC presented a survival outcome higher than expected in the overall population, according to previously reported data. An ancillary study is ongoing to evaluate possible biomarkers as prognostic factors on available tumor samples. No significant financial relationships to disclose.
Is there a palliative benefit of gemcitabine (G) plus fluoropyrimidines (F) in patients (pts) with refractory colorectal cancer (CRC)?
Authors: M. Y. Merl, T. Pham, C. J. Hoimes, M. W. Saif
Journal: Journal of Clinical Oncology (2008)

20655 Background: CRC is the second most common cause of cancer-related mortality in Europe and North America. Integration of newer cytotoxic and targeted agents have significantly improved the survival of pts with CRC. Pts with CRC are living longer, and challenges arise to offer them palliative treatment after they fail standard regimens. F (5-FU/capecitabine) with oxaliplatin or irinotecan are the most commonly used regimens in pts with advanced CRC. G, a nucleoside analog of deoxycytidine acts synergistically with F to enhance binding of thymidylate synthase and increase inhibition of DNA synthesis. Studies have indicated that F + G (FG) can be combined with acceptable toxicity at nearly full doses. FG could be an alternative for refractory CRC pts who failed standard therapy and have limited options. The objective of this review is to evaluate literature for evidence of efficacy and safety of FG in treating refractory CRC pts. Methods: PubMed (1950 through 2007), Ovid, Cochran and the American Society of Clinical Oncology abstract database were searched using the terms gemcitabine, fluorouracil, capecitabine, and colorectal cancer to identify relevant studies. Only studies using FG in CRC pts were reviewed and analyzed. Results: Forty-two advanced CRC pts were evaluated in two phase I studies and 179 pts were evaluated in five phase II studies. FG was used as 1st line therapy in two studies and as 3rd line therapy in three studies. The overall response rate (ORR), stable disease (SD), median time to tumor progression (TTP), and median overall survival (OS) were reported in the Tablebelow. The most commonly reported grade 3–4 toxicities were neutropenia, thrombocytopenia, and mucositis. Conclusions: FG is clinically active in pts with refractory CRC with prolonged median TTP and acceptable toxicities. FG may be considered for pts with advanced CRC refractory to primary treatment without other options or not eligible for clinical studies. Studies are underway to evaluate FG with other agents. Efficacy and Safety of FG in Treatment of Advanced CRC Phase (N) Regimen (Dose) Response Rate Grade 3-4 toxicity I (42) Gemcitabine (900-1,000 mg/m2) with either 5-FU (450 mg/m2)/folinic acid (100 mg/m2) or capecitabine (1,660 mg/m2/day) ORR: 38% Anemia: 7% Neutropenia: 7-11% II (179) Gemcitabine (900-1,250 mg/m2) with either 5-FU (200 mg/m2 CI or phase I dose) or capecitabine (2,500 mg/m2/day) ORR: 30-38.3% Neutropenia: 4-31% SD: 45-70.5% Thrombocytopenia: 6-18% TTP: 4-8.3 + months Mucositis: 5-8% No significant financial relationships to disclose.
Randomized phase II trial of bevacizumab and temsirolimus in combination with vinorelbine (V) and cyclophosphamide (C) for first relapse/disease progression of rhabdomyosarcoma (RMS): A report from the Children’s Oncology Group (COG).
Authors: Leo Mascarenhas, William H. Meyer, Elizabeth Lyden, David A. Rodeberg, Daniel Joseph Indelicato, Corrine M Linardic, James Robert Anderson, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2014)

10003 Background: Patients with RMS have a poor prognosis at first relapse/disease progression. VC has activity in RMS and preclinical data supports the use of bevacizumab and temsirolimus in RMS. Methods: Patients with biopsy proven RMS, < 30 years of age and unfavorable prognosis at first relapse/progression were eligible. Entry criteria were: life expectancy > 8 weeks, performance status < 2, adequate organ function and written informed consent. Patients were randomized between two regimens administered every 3 weeks for a maximum of 12 cycles: Regimen A- V 25 mg/m2 intravenously (IV) days 1 & 8, C 1.2 gms/m2 IV day 1, bevacizumab 15 mg/Kg IV day 1; b) Regimen B- VC identical to regimen A, temsirolimus 15 mg/m2 IV days 1, 8 & 15. Primary endpoint was event free survival (EFS) at 6 months. Disease response at week 6 was assessed using RECIST. The study had a phase 2 screening design and was powered to detect a 15% difference in EFS between the two regimens (α=0.2, 1-β=0.8, 2-sided test). Interim analysis was planned when 30%, 50% and 75% of the expected events occurred. Results: 87 of the 100 planned patients were enrolled when the trial was closed following the second interim analysis after 46 events occurred in 68 patients with sufficient follow-up. The O'Brien Flemming boundary at this analysis corresponded to a 2-sided p value of 0.0582 with an observed 2-sided p value of 0.0031 favoring the regimen with temsirolimus. The 6 month EFS for regimen A was 50% (95% CI 32%, 66%) and for regimen B was 65% (95% CI 44%, 79%). The response rate observed for regimens A and B were 32% and 47% respectively (p=0.22). The rate of progressive disease on regimen A was 26% compared with 9% on regimen B. Treatment was well tolerated. No unexpected toxicities were observed. Febrile neutropenia was the most common adverse event on both regimens. Oral mucositis and hypertriglyceridemia were noted only on regimen B. Conclusions: Patients randomized to VC+ temsirolimus had a superior EFS compared to VC+ bevacizumab. Temsirolimus has been selected by COG for further investigation in newly diagnosed patients with intermediate risk RMS. Clinical trial information: NCT01222715.