tbuckley/cabot-search huggingface dataset:
Safety and efficacy of adjuvant modified FLOX for patients (pts) with stage III colorectal cancer (CRC) treated in the community.
Authors: Bruno Mendonca Protasio, Adriana Reis Brandao Matutino, Liana Valente Lage, Iuri Amorim De Santana, Ricardo Emanuel De Oliveira Ramos, Rafael Caires-Lima, Inacelli Queiroz De Souza Caires, Rachel Pimenta Riechelmann, Daniel Fernandes Saragiotto, Jorge Sabbaga, Paulo Marcelo Hoff
Journal: Journal of Clinical Oncology (2015)

760 Background: Based on the NSABP-C07 trial, FLOX became one of the standard adjuvant regimens for pts with stage III CRC. However, its efficacy and safety have not been evaluated outside of clinical trials. Methods: Retrospective analysis of all consecutive stage III CRC pts who received adjuvant chemotherapy with modified FLOX (5-FU bolus 500 mg/m 2 and bolus of LV 20 mg/m 2 for 6 consecutive weeks and oxaliplatin 85 mg/m 2 in 2 hours-infusion at weeks 1, 3 and 5, every 8 weeks). Logistic regression (LR) multivariable models were used to identify predictors of relapse at 2 years and factors associated with grade ≥3 toxicity. Two-sided p&lt;0.05 were significant. Results: From Feb 2007 to Oct 2013, 267 pts were eligible: median age was 59 years, 53.2% were male and 83 (32.2%) were operated emergently. Most pts (68.2%) had stage IIIB CRC, with a median of 21 (range: 1-119) lymphnodes resected. Pathology characteristics: 32 (12%) were poorly differentiated, 132 (49.4%) had angiolymphatic invasion and 75 (28.1%) had perineural invasion. Median time to chemotherapy initiation was 63 days (range: 10-188). With a median follow-up of 24 months, 67 (25.1%) pts recurred. In LR, urgent surgery (odds ratio [OR]=1.9, 95% IC: 1.03-3.49; p=0.039), angiolymphatic invasion (OR=1.99, 1.09-3.64; p=0.024), and delay/dose reduction of chemotherapy (OR=2.62; 1.45-4.72; p=0.001) were predictors of recurrence at 2 years. Any grade ≥3 toxicity occurred in 98 (36.7%) pts, with diarrhea (16.1%), and neutropenia (15.3%) being the most frequent ones. A total of 9 (3.4%) pts died from any cause within 60 days of starting modified FLOX. Age ≥65 years (OR=2.6, 1.26-5.38; p=0.01) was associated with a higher risk of grade ≥3 toxicity in LR. Conclusions: The adjuvant modified FLOX was effective in stage III CRC pts treated in the community but offered significant risk of serious toxicity and death. This regimen should be probably restricted to fit pts who are ≤65 years. Also, similar to the stage II setting, we found that stage III CRC pts whose primary tumor were ressected emergently, those with angiolymphatic invasion or who received less dose-intense chemotherapy were at higher risk of recurrence.
A phase I, open-label, cohort study of two doses of coxsackievirus A21 given intratumorally in stage IV melanoma.
Authors: D. Shafren, B. M. Smithers, M. Formby
Journal: Journal of Clinical Oncology (2011)

8573 Background: Coxsackievirus A21 (CVA21: CAVATAK) is a naturally occurring Picornavirus, which induces mild upper respiratory symptoms during natural infection of humans. CVA21 also displays potent oncolytic activity against both in vitro cultures of cancer cells and against in vivo xenografts of human cancers in mouse models of melanoma, prostate cancer, breast cancer and multiple myeloma, all which exhibit high surface ICAM-1 expression. In mouse human melanoma xenograft CVA21 challenge models, progeny virus released from infected cells is capable of targeting adjacent cells, entering the systemic circulation, and destroying micro-metastatic foci. Methods: A single cutaneous melanoma deposit in nine stage IV melanoma patients (3 cohorts of 3 patients) was injected with 2 doses of CVA21 (1.0 x107TCID50 or 1.0 x108TCID50 or 1.0 x109TCID50) 48 hours apart. The viral inoculum was diluted to 10% of the target lesion volume in saline up to a maximum of 10mL. The average longest diameter of the injected lesions was 3.2 + 0.9 cm. Results: Nine patients tolerated two intralesional injections of CVA21 up to a final accumulated dose of 2 x 109 TCID50, as such a MTD of CVA21 in excess of 109 TCID50 was not reached. Following CVA21 injections, 5 of 9 (55.6%) patients experienced transient/stable reductions in injected tumor volume or tumor stabilization. No objective responses were observed, however, 2 patients displayed stable disease as assessed by RECIST 1.0 following CT evaluation. CVA21 viral RNA was detected by qPCR in 3 of 5 injected lesions on trial termination, even in the presence of high level serum anti-CVA21 neutralising antibody. Elevated levels of serum GM-CSF were observed from 2 patients displaying notable reductions in the volume of injected lesions, suggesting a possible immune-mediated anti-tumor response. No evidence of post-injection CVA21 excretion in urine, feces and sputum was observed. Conclusions: Potential anti-tumor activity and patient tolerability of intralesionally delivered CVA21, provides a solid foundation for Phase II investigations employing a multi-dose schedule to study the efficacy and safety of CVA21 in patients with late stage melanoma and other advanced solid cancers.
Clinical impact of routine serial multigated acquisition scans (MUGA) in patients with relapsed ovarian cancer exposed to pegylated liposomal doxorubicin (PLD)
Authors: M. S. Go, J. D. Cohen, M. S. Shahin
Journal: Journal of Clinical Oncology (2008)

5589 Background: Ovarian cancer patients are a difficult to treat population as most of them have been previously treated by a combination of chemotherapeutic agents and at least a platinum and taxane based regimen. Several studies have suggested that pegylated liposomal doxorubicin (PLD) administered at cumulative dose of less than 550 mg/m2 appears to be effective and with reduced risk of cardiotoxicity. Although the cumulative dose in these patients typically has been <240 mg/m2, cardiac function monitoring by serial MUGA scans are routinely employed. The practice of continued monitoring should be weighed against the cost-benefit ratio and should be re- evaluated. Method: A retrospective chart review was performed in our institution from 1985–2006. Patients who were included in the study were women from 30–85 years of age with relapsed ovarian cancer and have been treated with PLD. Age, stage, performance status, previous exposure to anthracycline therapy, presence of cardiac risk factors, and cumulative doses were analyzed against determination of LVEF through serial MUGA scans. Statistical analysis was performed using SAS 9.1 (Cary, NC). Descriptive statistics were used to characterize patient demographics and the fisher exact test utilized for crosstab analysis. Results: 61 patients met the inclusion criteria. This population has received a median of 2 chemotherapy regimens prior to initiation of PLD. 13% of the patients enrolled have received prior doxorubicin therapy and 16% have cardiac risk factors. The cumulative dose of PLD delivered range from 40–732 mg/m2 with a median dose of 200 mg/m2. Serial MUGA scans were obtained only in 21% of the population. Of these, no patients experienced clinical evidence of heart failure and no patients experienced a decline in LVEF of < 50% nor a > than 10% reduction in their baseline values. Conclusions: The patient population in this study represents the majority of patients with relapsed ovarian cancer. The clinical impact of monitoring serial MUGA scans in patients exposed to PLD with cumulative doses less than 550mg/m2 seems to be superfluous and guidelines recommending its use should be reconsidered. No significant financial relationships to disclose.
Safety and efficacy of implanted central venous catheters during adjuvant treatment of breast cancer and in a general oncology population.
Authors: M. Wilson, D. J. Porter, A. Maher
Journal: Journal of Clinical Oncology (2011)

9124 Background: Increasingly, women are choosing to receive short courses of adjuvant chemotherapy via an implanted central venous catheter (CVC) due to the perceived risk of lymphoedema if peripheral access is used in the at-risk limb. Two serious complications of CVCs (right atrial thrombosis with haemodynamic collapse and a cerebral sinus thrombosis) caused us to question this and review the complication rates of CVCs during adjuvant chemotherapy for breast cancer, compared to all patients receiving therapy via CVCs. Methods: We reviewed the records of patients (pts) receiving chemotherapy at Auckland City Hospital via a CVC, who were identified from a prospective database of CVC insertions. Pt characteristics, treatment type, intra and post-operative complications were recorded. Results: Between 1 Jun 08 and 1 Dec 09, 376 pts had 385 CVCs inserted. 140 pts had 144 CVCs for adjuvant breast cancer therapy. Overall 89 pts developed 103 complications. 32 CVC related infections were recorded (8.3%), with bacteraemia in 14. 15 DVTs (3.9%) and 2 catheter occlusions from thrombus were identified 13-260 days post CVC insertion. CVC complications led to 50 hospital admissions in 38 (10.1%) pts with a median stay of 5 days (range 1-33). Median time to first complication was 43 days (range 0-430). 11 treatment delays resulted (median 7 days, range 7-90). 33 (8.6%) pts needed early CVC removal. Left sided CVCs had higher complication rates (OR 3.0 p<0.0001). No deaths occurred. Adjuvant breast cancer pts had 26 admissions (18 pts), 7 DVTs (4.9%), 16 CVC infections (11.1%) and 9 treatment delays (median 7 days, range 7-28). Dose intensity data will be presented at the meeting. Adjuvant breast cancer pts complication rates were higher compared with other adjuvant pts (OR 2.1 p<0.05) and all other pts (OR 1.8 p<0.02). No association was seen with chemotherapy regimen or BMI. Conclusions: Contrary to expectation, the risks associated with CVCs appear to be greater in women receiving adjuvant therapy for breast cancer than in other pts. The risks of these devices may outweigh any impact of peripheral venous access on lymphoedema incidence, which is not as yet objectively quantified, particularly after SLNB.
Results of functional testing and pharmacokinetics comparing ABP 215 to bevacizumab.
Authors: Richard Markus, Primal Kaur, Vincent Chow, Nan Zhang, Teresa Born, Quyen Huynh, Gwen Maher, Jyoti Velayudhan, Monique Howard, Kaz Reynhardt, Theresa Goletz
Journal: Journal of Clinical Oncology (2015)

711 Background: ABP 215 is a biosimilar candidate to bevacizumab (BEV), a monoclonal antibody (mAb) that binds and inhibits vascular endothelial growth factor (VEGF). Biosimilar mAbs are likely to have differences in product quality attributes due to different expression systems, bioprocess and purification, so demonstration of functional similarity and pharmacokinetic (PK) equivalence is the foundation for biosimilarity. Objectives: To assess functional similarity and PK equivalence of ABP 215 and BEV sourced from EU and US. Methods: Functional similarity testing included binding to VEGF and VEGF isoforms by surface plasmon resonance and to FcRn and FcγRIIIa. Inhibition of proliferation and VEGFR2 autophosphorylation was compared in endothelial cells. PK equivalence was evaluated in a randomized, single-dose, 3-arm study in healthy adult male subjects. Primary endpoints were area under the serum concentration-time curve from time 0 to infinity (AUC inf ) and maximum observed serum concentration (C max ). Secondary endpoints were safety, tolerability, and immunogenicity. Results: ABP 215 and BEV (EU) are functionally similar as previously presented. Binding affinity to VEGF was similar between ABP 215 (117 pM) and BEV (US) (126 pM) as was binding to VEGF 165 and VEGF 121 . Binding to FcRn was similar between ABP 215 (95-102%) and BEV (96-111%). Binding to FcγRIIIa was also similar; ABP 215 (108-115%) and BEV (85-93%). Potency in proliferation inhibition was similar between ABP 215 (91-97%) and BEV (91-96%), as was inhibition of autophosphorylation. After a single dose, geometric mean (GM) of C max and AUC inf for ABP 215 were 87.2 µg/mL and 29,400 µg.h/mL, for BEV (US) were 89.1 µg/mL and 29,600 µg.h/mL, for BEV (EU) were 84.7 µg/mL and 30,600 µg.h/mL. The 90% CIs of GM ratio for C max and AUC inf were within pre-specified equivalence criterion of 0.80 to 1.25 confirming PK equivalence. There were no adverse events (AEs) or serious AEs leading to study discontinuation. Treatment-related AEs were reported for 22.1% in ABP 215, 16.4% in BEV (US) and 22.4% in BEV (EU) groups; no subjects developed anti-drug antibodies. Conclusions: ABP 215 is similar to BEV in sensitive functional tests and equivalent to BEV based on results of the phase 1 PK study.
A phase Ib study of preoperative lapatinib, paclitaxel, and gemcitabine combination therapy in women with HER2-positive early breast cancer.
Authors: I. H. Park, K. S. Lee, H. S. Kang, Y. Kwon, S. W. Kim, S. Lee, S. Y. Jung, K. H. Shin, K. Ko, B. Nam, J. Ro
Journal: Journal of Clinical Oncology (2011)

e11069 Background: Previously, we reported that the addition of trastuzumab to paclitaxel/gemcitabine as neoadjuvant chemotherapy(NCT) had significantly increased the rate of pCR in HER2 positive early breast cancer (EBC). We conducted a phase I trial to determine the feasible dose for lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor, with paclitaxel and gemcitabine as NCT in HER2 positive EBC. Methods: In this phase I dose escalation study, cohorts of 3 to 6 patients received lapatinib (1,000mg or 1,250mg PO, daily), paclitaxel (80mg/m2, IV on day 1 and 8), and gemcitabine (1,000 or 1,200mg/m2, IV on day 1 and 8) every 21 days using a standard 3+3 design. Patients undergo lapatinib maintenance to complete 1 year treatment and receive adjuvant hormone therapy for 5 years as indicated. Results: Among 13 patients with EBC enrolled between August 2009 and June 2010, 12 patients (stage III; 11: stage II; 1) completed treatment. One patient withdrew the consent. The maximum tolerated doses (MTD) for the combination were lapatinib 1000mg once daily, paclitaxel 80mg/m2 and gemcitabine 1000mg/m2 days 1 and 8 every 21 days. Of these 12 patients, 1 patient developed dose-limiting grade 3 transaminase elevation; 3 patients dose-limiting grade 4 neutropenia. There was no notable decline in ejection fraction of left ventricle during lapatinib treatment. Eleven of 12 patients showed clinical PR with 3 patients (25%) achieved total pCR, and 5 (42%) achieved tumor pCR. Six patients (50%) underwent breast conserving surgery. There was no apparent relationship between lapatinib dose intensity and tumor response. Median follow-up duration was 16.2 months (range, 6.5-20.7 months) and three patients are on lapatinib maintenance. Conclusions: The combination of lapatinib plus paclitaxel and gemcitabine was tolerable and there was no overlapping toxicity. Antitumor activity should be further assessed in a phase II clinical trial. Clinicaltrial.gov # NCT01133912. Funded by National Cancer Center Grant 0910320-3 and by GSK. Study drugs were supplied by GlasoSmithKline Korea for lapatinib, ShinPoong Pharm.Co.LTD for gemcitabine, and CJ Cheiljedang for paclitaxel.
Updated analysis of HERBIS-1: A phase ll study of trastuzumab (T-mab) in combination with tri-weekly S-1 plus CDDP in HER2-positive advanced gastric cancer.
Authors: Makio Gamoh, Naotoshi Sugimoto, Hiroto Miwa, Masahiro Tsuda, Shinichi Nishina, Hiroyuki Okuda, Hiroshi Imamura, Jin Matsuyama, Toshio Shimokawa, Daisuke Sakai, Yukinori Kurokawa, Yoshito Komatsu, Toshimasa Tsujinaka, Chikashi Ishioka, Hiroshi Furukawa
Journal: Journal of Clinical Oncology (2014)

98 Background: The HERBIS study demonstrated the promising antitumor activity and manageable toxicities of S-1 plus cisplatin and T-mab (SPT) regimen in patients (pts) with HER2-positive advanced gastric cancer (AGC) (Sugimoto et al. ASCO GI 2012, Abstract 70). We report the updated time-to event analysis. Methods: Main eligibility criteria were gastric or esophagogastric junction adenocarcinoma, HER2-positive, unresectable or recurrent, measurable lesion, no history of chemotherapy or radiotherapy, ECOG PS of 0-1 and adequate organ function. Pts received S-1(80-120mg / day) on days 1-14, cisplatin 60 mg/m 2 on day 1 and T-mab 8 mg/ kg on day 1 (6 mg/ kg from 2nd course) repeated every 3 weeks until disease progression. Primary endpoint was response rate (RR) and secondary endpoints were overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF) and adverse events. The planned sample size was 50 pts. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible and one patient did not receive any treatment. Therefore, the efficacy and safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate was 67.9% (95% CI: 53.7-80.1), and the disease control rate was 94.3% (95% CI: 84.3-98.9). Median OS was 16.0 months (95% CI: 13.3 - NaN), median PFS was 7.8 months (95% CI: 6.0 – 8.8) and median TTF was 5.7 months (95% CI: 4.2 - 7.1), respectively at the median follow-up time of 13.5 months. The main grade 3/4 adverse events were leukopenia 8%, neutropenia 36%, anemia 15%, increased creatinine 6%, hypoalbuminemia 9%, anorexia 23%, diarrhea 8% and vomiting 6%. Conclusions: SPT have promising antitumor activity and manageable toxicities in pts with HER2-positive AGC. Clinical trial information: UMIN000005739.
Emotional concerns in cancer survivors not treated with chemotherapy.
Authors: Tina Nikoomanesh, Melanie Goldfarb
Journal: Journal of Clinical Oncology (2016)

233 Background: Emotional concerns can impact quality of life in all cancer (CA) survivors, regardless of receipt of chemotherapy. Methods: Surgically treated CA survivors that were not treated with chemotherapy were identified in the 2010 LiveStrong Survey. Only patients that responded to all 9 categories of emotional concern questions were included (energy/fatigue, depression and mood, identity and grief/guilt, faith and spirituality, fear of recurrence, social anxiety, shame, concern for family, insecurity). A total emotional concern score was calculated (0-9) and independent t-tests or ANOVA identified factors that impacted the total score. After stratification by CA type, linear regression determined which factors, if any, were important predictors of having more emotional concerns. Results: Of 649 CA survivors, most were white (91.0%), insured (97.8%), employed/student (79.3%), married/domestic partner (76.2%), and had survived at least 5 years (69.8%); many were &gt; 40 years old (62.8%). The median number of reported emotional concerns was 4 (mean 4.3, SD 2.0) with 3.1% of patients reporting no concerns. Patients with brain or head/neck CAs had the highest scores (5.3, SD 1.5-1.7), whereas those with other endocrine tumors or melanoma had the lowest scores (3.9, SD 2.0-2.1), (p = 0.001). Additionally, age &lt; 40 at diagnosis, female gender, being employed, uninsured, having less education, and having received radiation (RT), hormone (HT), or other additional therapy all increased the emotional concern score (p &lt; 0.05); race/ethnicity, marital status, and income did not impact the score. After stratification by CA type, only the following increased emotional concerns: receipt of HT for breast CA (B = 0.30), being employed (B = 0.82) or retired (B = 0.41) for thyroid CA, female gender (B = 0.51) or receiving RT (B = 0.38) for bone/soft tissue CA, age &lt; 40 (B = 0.37) and receipt of other/HT (B = 0.31) for melanoma, and female gender for (B = 0.76) for other endocrine tumors. Conclusions: Significant emotional concerns are reported by surgically treated cancer survivors not treated with chemotherapy. These concerns are most influenced by cancer type and treatment, but not race/ethnicity, marital status, or income.
Long-Term Prophylaxis In Children, Adolescents and Young Adults with Von Willebrand Disease – First Results of a Cohort Study
Authors: Susan Halimeh, Anne Kruempel, Hannelore Rott, Nadja Bogdanova, Ulrich Budde, Daniela Manner, Britta Faeser, Rolf M. Mesters, Ulrike Nowak-Gottl
Journal: Blood (2010)
Does nonsurgical management for localized kidney cancer equate to active surveillance in the SEER-Medicare population?
Authors: Marc C. Smaldone, Brian Egleston, Simon Kim, Elizabeth Handorf, Daniel M. Geynisman, Yu-Ning Wong, Robert G. Uzzo, Alexander Kutikov
Journal: Journal of Clinical Oncology (2014)

444 Background: Differentiating between patients with small renal tumors not selected for treatment from those who choose elective active surveillance (AS) using administrative data is a significant challenge. Using active treatment as a benchmark, our objective was to compare survival outcomes between all patients with localized kidney cancer who received non-surgical management (NSM) with those meeting more stringent NSM criteria who are more likely to clinically resemble AS. Methods: Using linked SEER-Medicare data, we identified all patients ≥66 years old with localized T1 (&lt;7cm) Renal Cell Carcinoma from 1995-2009. Treatment groups were defined as active treatment (partial or radical nephrectomy), all NSM (no treatment within 6 months of diagnosis), and stringent NSM (further exclusion of patients with lack of imaging or presence of hospice claims). Patients undergoing ablative treatment were excluded from analyses. Overall and cancer specific mortality were assessed using Cox and Fine and Gray proportional hazard models with propensity score based weighting. Results: Of 15,450 identified patients, 2,089 (13.5%) underwent NSM. Of these, 1,182 (56.6% of NSM, 7.7% of overall sample) met stringent NSM criteria. Following adjustment, the all NSM group demonstrated significant increases in cancer specific (sHR 1.91 [CI 1.26-2.88]) and overall (HR 1.49 [CI 1.16-1.92]) mortality compared to patients undergoing active treatment. In contrast, for patients meeting stringent NSM criteria, these differences in cancer specific (sHR 1.48 [CI 0.82-2.68]) and overall (HR 1.33 [CI 0.998-1.77]) mortality were attenuated and no longer met statistical significance. Conclusions: Compared to active treatment, patients meeting stringent NSM criteria demonstrated improved survival outcomes when compared to all-comers with localized kidney cancer who were managed non-surgically. Our findings support that a validated, claims-based algorithm that more accurately identifies patients undergoing elective AS is needed to objectively assess the safety and effectiveness of this clinical strategy.