tbuckley/cabot-search huggingface dataset:
Capecitabine (X) compared to X + erlotinib (E) as first-line treatment in patients (pts) with metastatic colorectal cancer (MCRC): Interim efficacy results from a randomized phase II study
Authors: M. Vincent, I. Kerr, B. Dingle, M. J. MacKenzie, M. Sanatani
Journal: Journal of Clinical Oncology (2007)

14560 Background: The oral fluoropyrimidine X (Xeloda®) has efficacy, safety and convenience benefits vs. 5-FU/LV in adjuvant / first-line CRC. E (Tarceva®) inhibits epidermal growth factor receptor (EGFR), which predicts poor prognosis. A randomized open-label phase II study was performed to establish activity of X alone vs. X + E (XE) in first-line. Methods: Pts (ECOG PS 0–2 and/or elevated LDH) with MCRC not eligible for immediate surgical metastatectomy and unwilling/unable to undergo combination chemotherapy were randomized to X (1000mg/m 2 /d bid d1–14 q3w) or XE (X 1000mg/m 2 /d bid d1–14 q3w + E 150mg/d). A third arm (E alone) was included but dropped after 13 pts, following safety committee review of progressions at first CT scan. Primary endpoint: time to progression (TTP). Results: 59 pts (median age 65y, range 46–84; 44 M, 15 F) have been accrued (X=21; XE=25; E=13). Mean time on study: 3.8 months (range 0.2–12). 9 pts are on active treatment, 21 pts on follow-up and 29 pts have died. Interim efficacy results are available for 50 pts (X n=15; XE n=22, E n=13). There were no significant differences in response rate, median TTP (4.9 vs. 9.2 months) and median overall survival (18.2 vs. 15.1 months) for X vs. XE. Grade 3 adverse events (AEs) with X were diarrhea, nausea, hand-foot syndrome (HFS), angina, dyspnea (all 5%). Corresponding rates of grade 3 AEs with XE were diarrhea (20%), fatigue (16%), stomatitis (12%), HFS (8%), vomiting (8%), dehydration (8%), thrombosis, weight loss, decreased appetite, dry eyes, headache, anxiety, abdominal pain, anorexia, hyponatremia (all 4%). The only grade 4 AEs were skin rash (4%) and subjective weakness (4%) - both XE. Conclusions: Interim results indicate that XE is at least as effective as X alone in first-line MCRC. Recruitment is continuing and further follow-up may help fully determine the potential benefits of adding E to X. [Table: see text] No significant financial relationships to disclose.
High Expression of Activation-Induced Cytidine Deaminase and in Vivo Class Switch Recombination in Mantle Cell Lymphoma: Further Support for Antigen Involvement in Lymphomagenesis
Authors: Aliki Xochelli, Fotini Marantidou, Evangelia Stalika, Lesley-Ann Sutton, Alba Navarro, Jana Supikova, Kyriakos Karypidis, Maria Chatzouli, Myriam Boudjogra, Christer Sundstrom, Hana Skuhrova Francova, Achilles Anagnostopoulos, Sarka Pospisilova, Theodora Papadaki, Christiane Pott, Frederic Davi, Elias Campo, Richard Rosenquist, Chrysoula Belessi, Kostas Stamatopoulos
Journal: Blood (2012)
A meta-analysis of biochemotherapy (BCT) for the treatment of metastatic malignant melanoma (MM)
Authors: R. El-Maraghi, S. Verma, M. Charette, B. Markman, I. Quirt
Journal: Journal of Clinical Oncology (2004)

7529 Background: Systemic approaches to therapy of metastatic MM include cytotoxic chemotherapy, immunotherapy such as interferon-alpha (IFN) and interleukin-2 (IL-2), and more recently BCT. Methods: A systematic review of the literature regarding BCT for treatment of metastatic MM was conducted using MEDLINE, CANCERLIT, Cochrane Library and Physician Data Query clinical trials databases. Relevant articles and abstracts were selected and reviewed by one member of the MDSG and methodologists. All published reports including abstracts for randomized controlled trials (RCTs) and single-arm phase II trials involving BCT were considered. An estimate of the effect of BCT on overall response rate (ORR), time to progression (TTP) and overall survival (OS) was determined using pooled data from published reports of individual RCTs. Results: Nine RCTs, 8 randomized phase II trials and 39 single-arm phase II trials were identified. Six studies compared chemotherapy alone to chemotherapy plus IL-2 and IFN. In only one study, BCT was superior for ORR (48% vs. 25%, p=0.001) and median survival (11.9 vs. 9.2 months, p=0.06) while a second demonstrated an improved ORR (44% vs. 27%, p=0.071) but a lower median survival (10.7 vs. 15.8 months, p=0.052). The remaining four studies showed no significant differences in ORR, TTP or OS. A pooled meta-analysis demonstrated that BCT was superior to chemotherapy for ORR (relative risk (RR)=1.49, CI 1.21–1.83, p=0.0002), and delayed TTP at six months (RR=0.82, CI 0.72–0.94, p=0.004) but not one-year survival (RR=0.89, CI 0.77–1.03, p=0.13). Therapy was toxic but quality of life did not seem to be impaired. Grade 3 and 4 toxicities were common. Conclusions: BCT is associated with higher ORR compared to standard therapy but does not have a meaningful impact on survival in patients with metastatic MM. Due to the toxicity of BCT, treatment should be restricted to experienced centres. No significant financial relationships to disclose.
Capecitabine, oxaliplatin, radiotherapy, and excision (CORE) in patients with MRI-defined locally advanced rectal adenocarcinoma: Results of an international multicenter phase II study
Authors: H. Rutten, D. Sebag-Montefiore, R. Glynne-Jones, E. Rullier, M. Peeters, G. Brown, E. Van Cutsem, S. Ricci, C. J. Van de Velde, P. Quirke
Journal: Journal of Clinical Oncology (2006)

3528 Background: The addition of chemotherapy to preoperative radiotherapy (RT) may reduce distant recurrence and increase tumor resectability. The CORE study evaluated oxaliplatin, capecitabine, and RT (XELOX-RT) followed by total mesorectal excision (TME), then adjuvant XELOX in patients (pts) with MRI-defined locally advanced rectal cancer. Methods: MRI inclusion criteria: tumor beyond mesorectal fascia, tumor ≤2 mm from mesorectal fascia, or T3/4 tumor &lt;5 cm from anal verge. Chemoradiation (CRT) was 45 Gy RT (1.8 Gy/dose) 5 days/wk for 5 wks, weekly oxaliplatin 50 mg/m 2 , and twice-daily capecitabine 825 mg/m 2 on each day of RT. Surgery was 6–8 wks after completing XELOX-RT. Pts with R0-R1 resection were to receive XELOX for 6 cycles. Central radiologic and histopathologic review were key study components. Processes to determine histopathologic response and circumferential resection margin (CRM) were predefined. The primary endpoint was pCR rate (planned n=70 evaluable pts). Results: Between July 2003 and Dec 2004, 87 pts were enrolled; 85 pts received XELOX-RT and 79 had TME. Seventy pts (82%) had R0-R1 resection, with a 67% R0 rate (n=57) by Quirke methodology (CRM &gt;1 mm). The pCR rate was 13% (10/78 pts assessable for tumor response; 95% CI, 5.46–20.34%). Tumor regression grading showed excellent response in 35% and poor response in 64% of pts. Of 60 pts evaluated by central MRI review for response by RECIST, the overall response rate was 70% (7% complete; 63% partial response). Preoperative grade (G) 3/4 adverse events (% of pts; evaluable n=85) included diarrhea 16% (12% G3), sensory neuropathy 1% (G3), neutropenia 1% (G3), and hand-foot syndrome 1% (G3). More than 90% of pts received full dose radiotherapy. Conclusions: Significant tumor regression and a high R0 resection rate were achieved using a CRT regimen of preoperative oxaliplatin, capecitabine, and 45 Gy RT, with acceptable toxicity. Central histopathologic and radiologic review data, together with safety and efficacy results for both preoperative CRT and postoperative chemotherapy, will be presented. [Table: see text]
An impact of pelvic MRI (PMRI) to radiotherapy (RT) target volumes definition in prostate cancer patients (pts).
Authors: Keren Rouvinov, Wilmosh Mermershtain, Olga Beloshicki, Shmuel Ariad, Konstantin Lavrenkov
Journal: Journal of Clinical Oncology (2015)

78 Background: PMRI is a standard pre-RT evaluation procedure in pts with intermediate and high-risk prostate cancer. We conducted a retrospective study to evaluate an influence of PMRI to delineation of RT clinical target volume (CTV). Methods: Medical records of prostate cancer pts treated with intensity-modulated RT (IMRT) in single institution retrieved and examined retrospectively. Initial risk group affiliation was defined using D'Amico method. PMRI reports of pts with intermediate and high-risk prostate cancer were reviewed and risk group affiliation was re-defined in regards of T- and N-stage. IMRT treatment plans were re-assessed. In regards to PMRI T-stage, extra-capsular extension (ECE) and seminal vesicles invasion (SVI) were included to high-dose CTV. Pelvic lymph nodes (PLN) were planned to treat in all high-risk pts. PLN considered pathological by PMRI were included to separate CTV to receive RT dose higher than unaffected PLN stations. Results: Between 2008 and 2014, 169 pts with intermediate and high-risk prostate cancer underwent PMRI at around 1 month before commencing IMRT. Initially, 89 pts were affiliated to intermediate-risk and 80 to high-risk group. In general, PTV-changes based on PMRI data required in 77 pts (45.5%). Thirty seven of 89 intermediate-risk pts (41.6%) have been switched to high-risk group, necessitating irradiation of PLN. ECE and SVI were included to high-dose CTV in 64 (37.8%) and 29 pts (17.2%) respectively. PLN were thought pathological in 10 pts (5.9%), which demanded contouring of a separate CTV. Conclusions: In our series PMRI-scans had a significant impact on RT target coverage decision in pts with intermediate and high-risk prostate cancer.
Clinical outcome of recombinant human soluble thrombomodulin (rTM) for patients with disseminated intravascular coagulation (DIC) complicating advanced solid cancer: Retrospective analysis.
Authors: Shin Takahashi, Kohta Ohuchi, Shunsuke Kato, Hideki Shimodaira, Yuichi Kakudo, Shoko Akiyama, Kozue Yoshida, Masatoshi Shiono, Yoshinari Okada, Shunsuke Sugiyama, Naoko Saito, Jin Lee, Takayuki Oishi, Hidekazu Takahashi, Yuki Yoshino, Chikashi Ishioka
Journal: Journal of Clinical Oncology (2012)

e19611 Background: Disseminated intravascular coagulation (DIC) is a syndrome characterized by the activation of coagulation leading to systemic microvascular thrombosis. DIC is frequently observed in patients with hematologic malignancy and often in patients with advanced cancer. Recombinant human soluble thrombomodulin (rTM) has been introduced as a new type of anti-DIC agent for clinical use in patients with hematological cancer or infectious disease. However, the efficacy for advanced solid cancer has not been elucidated. Methods: All patients with DIC complicating advanced solid cancer who were treated by rTM in Tohoku university hospital from December 2009 to November 2011 were enrolled in this retrospective study. DIC was diagnosed and scored according to the diagnostic criteria established by the Japanese Ministry of Health and Welfare (JMHW DIC criteria). Change in DIC score and period of overall survival (OS) after treatment of rTM (380U/kg/day) were evaluated. The Kaplan-Meier method was used to calculate OS. Results: Twenty-two patients (32% female) were enrolled. The median age was 61.5 (r: 32-82). The primary organs were 7 stomach, 3 colorectal, 2 esophageal and 10 other cancers. DIC score (63.6%), FDP (54.5%), PT-INR (45.4%), FBG (36.4%) were kept or improved in these patients between day 1 and day 5 in rTM treatment. Median OS (mOS) was 30 days (r: 2–301). Subgroup analyses revealed that mOS was longer in patients who underwent chemotherapy following rTM treatment than in patients who did not (114 days vs. 10 days, p = 0.0083). Patients with better ECOG PS (&lt;2 vs. &gt;3; 114 days vs. 15 day, p = 0.018), smaller number of chemotherapy treated before DIC (&lt;2 vs. &gt;3; 69 days vs. 6 days, p = 0.0008) also showed better mOS. No critical complication was observed. Conclusions: This study showed that rTM was effective and safe for patients with DIC complicating advanced solid cancer. PS and number of chemotherapy regimens could be predictive factor of rTM. We considered that rTM yield the chance of chemotherapy to advanced cancer patients with DIC by preventing deterioration of DIC.
“Healthy heroes”: A unique exercise intervention in pediatric survivors of posterior fossa brain tumors.
Authors: A. M. Walsh, M. J. Barnes, K. Ross, L. Futch, J. C. Klapow, R. Davis, E. Kvale, K. Whelan, A. Madan-Swain
Journal: Journal of Clinical Oncology (2010)

e19672 Background: Childhood brain tumor survivors fatigue more easily and are more sedentary than same age peers. Cancer treatments can impair balance and coordination. Few studies have attempted to address these issues. “Healthy Heroes” is a community-based exercise intervention designed to improve exercise adherence, increase physical activity, and improve quality of life in brain tumor survivors. Methods: Participants include posterior fossa brain tumor survivors, ages 6 to 18 years and at least 1 year from the end of treatment. All participants receive pre- and post- assessments of strength, endurance and flexibility. Participants and parents complete validated paper-and-pencil measures of sleep, fatigue and quality of life (QOL). Survivors are assigned a Life Skills Coach for six weeks. During each session participants are evaluated on mastery of learned skills, learn new physical skills, set goals, and problem solve barriers to engaging in physical activity. Participants are rewarded throughout the study using ChipRewards, which reinforces participants for specific behaviors with chips which can be redeemed for prizes. Results: Recruitment and evaluation of participants in this study is ongoing. Pilot data is reported on 3 participants: 2 males ages 8 and 16 years, and 1 female age 16 years. Self reported activity averaged 10.7 hours a week. Improvement in sleep as measured by the Sleep Health Questionnaire for School Aged Children, was noted by all participants or their parents. Two of three patients and all parents reported improvement in QOL (as measured by the PedsQL4.0 inventory). Measures of joint range of motion (ankle dorsiflexion), flexibility (popliteal angle), and strength (quadriceps strength with knee extension) showed improvement in at least 2 of the 3 participants. All patients demonstrated improvement in the timed pacer fitness test. Conclusions: Pilot data indicates that this intervention is both feasible and beneficial with posterior fossa brain tumor survivors. Additionally, this exercise program positively impacted sleep, QOL, strength, flexibility and cardiovascular fitness. No significant financial relationships to disclose.
India meets target to reduce tuberculosis burden
Authors: C. Travasso
Journal: BMJ (2015)

India has met the 2015 target to reduce the incidence, prevalence, and mortality rate of tuberculosis (TB), but the country still accounts for 23% of the world’s TB cases, a report from the World Health Organization has found.

The targets set out in WHO’s annual Global Tuberculosis Report were that TB incidence should be falling (based on the United Nations’ millennium development goal 6) and that TB prevalence and mortality rates should be halved compared with their 1990 levels. 

Between 1990 and 2014 the prevalence of TB in India fell …
Final results of a large, community-based, prospective study evaluating the impact of first and subsequent cycle pegfilgrastim on neutropenic events in patients receiving myelosuppressive chemotherapy
Authors: H. Ozer, B. Mirtsching, M. Rader, B. Ding, D. Truscinski, L. Dreiling
Journal: Journal of Clinical Oncology (2006)

8569 Background: Neutropenia is the major dose-limiting complication of myelosuppressive chemotherapy (CT). The Awareness of Neutropenia in CT (ANC) Study Group has prospectively documented cycle 1 febrile neutropenia (FN) in 8% of patients (pts) receiving CT with or without growth factor support in community practice. Our study was conducted to assess the impact of first and subsequent cycle pegfilgrastim use on neutropenic events in pts receiving CT in community practice. Interim data were previously reported (Ozer ASCO 2005). Methods: Pts ≥18 years with cancers other than leukemia or MDS were eligible, including pts with major comorbidities. Key exclusion criteria of this open-label study were weekly CT or concurrent radiotherapy (RT). Pts were to receive pegfilgrastim 6 mg ∼24 hours after CT (min 4 cycles planned). Primary endpoints were neutropenic hospitalization and CT dose delays and reductions; additionally, FN (absolute neutrophil count &lt;1×10 9 /L with temperature ≥38.2 o C) was measured. Results: 319 centers enrolled 2,249 pts (2,500 planned); 2,112 patients who received CT and pegfilgrastim after proper consent were included in final analyses. Most pts were women (75%). Major tumor types included: breast (46%), lung (16%), and ovarian (8%) cancers, and lymphoma (18%). 36% of pts were ≥65 years (mean age [SD]: 59 [12.8]), 55% had stage 3/4 or extensive disease, 23% received prior CT, 17% received prior RT, and 27% had a significant comorbidity. Neutropenic complications occurred infrequently (table). FN was experienced by 3.6% (95% CL: 2.8, 4.5) of pts in cycle 1 and in 6.3% (5.3, 7.5) in all cycles. Serious adverse events were consistent with toxicities observed in pts receiving CT. Conclusions: Pts treated in community practice receiving pegfilgrastim in every cycle of myelosuppressive CT experienced a low incidence of neutropenic complications and alterations in CT dose and schedule due to neutropenia. [Table: see text] [Table: see text]
Targeting Therapy for Resistant Multiple Myeloma with a Novel Inhibitor of NF-KB, NPI-1387.
Authors: Dharminder Chauhan, Ta-Hsiang Chao, Deli He, Teru Hideshima, Laurence Catley, Young-Ger Suh, Robert Schlossman, Saskia Neuteboom, Michael A. Palladino, Kenneth C. Anderson
Journal: Blood (2005)
Optimal duration of chemotherapy (CT) for advanced non-small cell lung cancer (NSCLC) in the first- and second-line settings
Authors: F. Grossi, O. Belvedere, C. Defferrari, A. Brianti, A. Follador, E. Rijavec, T. Ceschia, P. Pronzato, G. Fasola, M. Aita
Journal: Journal of Clinical Oncology (2009)

e19037 Background: No difference in efficacy has been observed between 3 or 4 vs 6 cycles of 1st line CT in patients (pts) with advanced NSCLC. Although longer treatment may improve progression-free survival, this must be weighed against increased toxicity and potential for worse quality of life. There are no prospective, randomized data on the optimal duration of 2nd line CT. The aims of this retrospective study were to (i) confirm the lack of impact of treatment duration on response rate in 1st line NSCLC and (ii) investigate the impact of treatment duration in the 2nd line setting. Methods: Eligible pts had received at least 4 cycles of 1st line (n=95) or 2nd line (n=55) CT for stage IIIB/IV NSCLC in clinical trials of the ATOM group, Udine, Italy, or the National Cancer Institute, Genoa, Italy and achieved stable disease or responded to treatment; trials included one in the elderly, and the addition of biological agents to CT. Response was assessed according to RECIST after alternate CT cycles and tumor dimensions recorded. The proportion of pts achieving a complete or partial response, as well as its timing and any subsequent tumor shrinkage, were analyzed by treatment line. Results: In the 1st line setting, 48 of 95 pts responded; they did so after 2 (29 pts, 61%), 4 (15 pts, 31%) and 6 cycles (4 pts, 8%). In these pts, 16 (55%) and 9 (41%) pts who had responded by the 2nd and 4th cycle respectively and continued on treatment showed further tumor shrinkage; the median further reduction in tumor size was 16% (range 1–52%) and 6% (range 1–11%), respectively. In the 2nd line setting, 12 of 55 pts responded; they did so after 2 (3 pts, 25%), 4 (7 pts, 58%), and 6 cycles (2 pts, 17%). One and two pts who had responded by the 2nd and 4th cycle respectively and continued on treatment showed further tumor shrinkage of 25%, 5% and 24%, respectively. Conclusions: Approximately 90% of CT-naive pts who responded did so by the 4th cycle; most such pts achieved only minor tumor reduction with further CT and did so at the likely expense of increased toxicity. In the 2nd line setting the achievement of response appeared slower. These results support the discontinuation of 1st CT after 4 cycles and suggest the same is true for 2nd line CT. No significant financial relationships to disclose.
Phase II trial of the novel epothilone ZK-EPO in patients with platinum resistant ovarian cancer
Authors: G. J. Rustin, N. S. Reed, G. Jayson, J. A. Ledermann, M. Adams, C. Stredder, A. Wagner, M. Giurescu
Journal: Journal of Clinical Oncology (2007)

5527 Background: The rationally designed, fully synthetic epothilone ZK-EPO has demonstrated significant activity against ovarian cancer cell lines. The results of the first completed phase I study (one 30-min infusion q3w) indicated good tolerability, with peripheral neuropathy as the most common toxicity; signs of activity, including objective responses, were reported. A randomised phase II trial was performed to determine the efficacy, safety and tolerability of 2 infusion durations in patients with platinum-resistant ovarian cancer. Methods: Eligible patients were at first or second relapse, had a platinum-free interval of &lt;6 months, and disease evaluable by RECIST or, if not measurable, by CA125 (GCIG criteria). Patients were randomised to receive 3-hour or 30-min infusions of 16 mg/m 2 ZK- EPO administered 3-weekly. Simon’s two-step design was used; 13–34 patients were to be accrued per arm. An arm would be continued if at least 2/13 patients responded. The drug would be considered efficacious if ≥6/34 patients responded. Results: To date, 63 patients have entered the study (accrual completed November 2006). Data is currently available on the 30 patients in step 1. Four patients were excluded from efficacy analysis due to tumor histology (clear or mucinous), as per protocol. 24 patients were taxane pre-treated. 4/13 patients responded in the 3-hour arm so accrual continued; in the 30-min arm 1/13 responded. A total of 101 infusions were administered to patients in step 1. The most common drug-related toxicity &gt;grade 1 in the 3-hour and 30-min arm was grade 2–3 peripheral sensory neuropathy (3-hour: 9/15 patients, 30 min: 5/15 patients). Two patients withdrew because of neuropathy, both in the 3-hour arm. Other drug-related toxicities &gt;grade 1 occurring in &gt;1 patient were fatigue (n=3), arthralgia (n=3), nausea (n=3) and lethargy (n=2). Conclusion: Preliminary results indicate that ZK-EPO, administered as a 3-hour infusion at a dose of 16 mg/m 2 , has promising activity against platinum-resistant ovarian cancer. Updated response data on all patients will be presented. Peripheral neuropathy currently appears to be the only noteworthy toxicity of ZK-EPO. [Table: see text]