tbuckley/cabot-search huggingface dataset:
Investigation of the tolerability of FOLFIRINOX in patients with unresectable advanced pancreatic cancer: Single-institution experience in Japan.
Authors: Kouichirou Miyashita, Takashi Sekikawa, Ken Shimada, Taikan Yamamoto, Yasuhiro Kaga, Toshikazu Nunoue, Yu Uto, Yu Kitahara, Atsushi Hisamatsu, Yusuke Saito, Kouji Kobayashi, Yasutaka Takinishi, Eriko Kinugasa
Journal: Journal of Clinical Oncology (2015)

487 Background: FOLFIRINOX therapy has contributed to the overall survival extension of unresectable advanced pancreatic cancer. This regimen is however associated with significant toxicity. And doing the treatment, while careful to toxicity at our institution. We investigated the tolerability of FOLFIRINOX for the treatment of unresectable advanced pancreatic cancer in clinical practice. Methods: We conducted a retrospective analysis of patients with unresectable advanced pancreatic cancer who received FOLFIRINOX between November 2012 and August 2014. FOLFIRINOX is as follows: irinotecan at 150 mg/m2; oxaliplatin at 85 mg/m2; 5-fluorouracil (5FU) at 400mg/m2 bolus, 2,400mg/m2 continuous infusion. Patients' characteristics, objective response, survival and toxicities were collected. Response were evaluated with RECIST version 1.1 and toxicities with NCI-CTCAE version 4.0. Results: 13 patients were includes (8 males and 5 females). Treatment eligibility criteria in our institution were Performance Status 0 or 1, and UGT1A1 polymorphisms were excluded. Median age was 58.6 years (41-74). Clinical stage IVa/IVb was 3/10. The mean number therapy was 7.7 (3-15) cycles. The toxicity of all grade was 100% and grade 3 was 80%. The non-hematological toxicities included nausea in 8 patients (61.5%) and anorexia in 9 (69.2%). The hematological toxicities included neutropenia in 12 patients (92.3%), of which 11 (84.6%) presented a grade 3/4 neutropenia. In patients who developed grade 3 neutropenia, the treatment of FOLFIRINOX could be continued once every three weeks (triweekly) without reducing the dose. Response rate was 38.5% (CR: 0, PR: 5, SD: 6, PD: 2) and disease control rate was 84.6%. Time to treatment failure was 175 days. Relative dose intensity was 95.0% for oxaliplatin, 88.9% for irinotecan, 81.9% for 5FU (bolus), and 95.6% for 5FU (continuous). Conclusions: In clinical practice, it is expected that FOLFIRINOX is an effective, well-tolerated regimen by reducing the dose or determining the appropriate dosing interval.
Surgical treatment of colorectal cancer in the advanced elderly: Does outcome justify treatment?
Authors: J. D. Cull, S. Kukreja, T. J. Hieken
Journal: Journal of Clinical Oncology (2011)

3629 Background: As the geriatric population increases, an increasing number of colon cancers are now diagnosed in the advanced elderly. Previous studies suggest higher mortality rates and adverse cancer outcomes in these patients. We undertook this study to examine differences in patient and tumor features, surgical treatment and outcome in colon cancer patients ≥80 years in comparison to younger patients. Methods: From our community teaching hospital Cancer Registry, we identified 720 consecutive colon cancer patients. Data were verified by chart, pathology and operative note review. Median follow up for surviving patients was 64 months. Patients were stratified into two groups (age <80 v age ≥80) to facilitate comparison. An SAS software package was used for statistical analysis. Results: Median patient age was 74 years (mean 71.5±0.5, range 26-100 years) and 196 pts were ≥80. 354 patients were male (49%). Patients ≥80 were more likely to have cardiac disease (66 v 41%, p=0.05), elevated preoperative CEA (53 v 42%, p=0.05), right-sided cancers (55 v 41%, p=0.0009) and less likely to have a +family history (22 v 33%, p=0.002) or laparoscopic surgery (10 v 18%, p=0.003). However, there was no difference in pulmonary disease, tumor size, tumor grade, stage, curative intent of treatment, #lymph nodes (LN) removed, proportion with ≥12 LN removed or #LN+. Patients ≥80 had increased perioperative mortality (5 v 1%) and were more likely to die of non-cancer causes (33 v 14%), p<0.0001. However, for patients <80 v those ≥80, cancer specific overall (77% 5Y, 72% 10Y v 72% 5Y, 67% 10Y, p=0.18) and disease-free (67% 5Y, 63% 10Y v 70% 5Y, 65% 10Y, p=0.41) survival were not significantly different. Conclusions: While perioperative mortality and non-cancer related deaths were significantly higher in pts ≥80 years, cancer-specific overall and disease-free survival were not significantly different. Our data support the concept that treatment of colon cancer in the advanced elderly should be robust, with curative intent, and not be based on chronologic age alone.
Examination of current Algoma District cancer program practices and local referral processes for patients with prostate cancer.
Authors: Daniella Febbraro, Silvana Spadafora
Journal: Journal of Clinical Oncology (2016)

352 Background: The Algoma District Cancer Program (ADCP) is located in Sault Ste. Marie, ON, Canada and services the needs of the 125,000 individuals residing in the Algoma District, which has an area of approximately 49,000 square kilometres. Due to its geographic isolation in Northern Ontario, maintaining standards of care can be challenging to deliver. The objective of this project is to document any improvements in the referral process and treatment of patients with prostate cancer at the ADCP since the arrival of new medical oncologists in July 2013. Methods: Patients who had been seen by a medical oncologist at ADCP from July 2013 to July 2015 were included in this study. Patient charts were analyzed in order to gather information including date of diagnosis, stage at time of referral, date of consult with medical oncologist, previous treatments trialed, and dates of treatment. Patients were divided into two groups, diagnosed prior to 2014 and after 2014, to examine progress at ADCP. Results: From July 2013 to July 2015, there were 73 patients seen by a medical oncologist at ADCP with a diagnosis of prostate cancer. Of these patients, 54 were diagnosed prior to 2014 and 19 were diagnosed after 2014. For all patients diagnosed prior to 2014, the average number of years from diagnosis to a medical oncology consult was 5.24 years, with the longest being 19 years for two patients. In comparison, for all patients diagnosed after 2014, a medical oncologist saw them only 0.26 years on average after they were diagnosed. Since 2014, lines of therapy administered after referral to medical oncology have become greater than before 2014. Specifically for stage IV prostate cancer patients, the average number of lines of therapy ordered by a medical oncologist has increased for patients diagnosed after 2014. Conclusions: Since the arrival of new medical oncologists at ADCP in July 2013, the average number of years after diagnosis that a patient is referred to the clinic has decreased, while the average lines of therapies utilized after their consult with a medical oncologist has increased, showing an improvement in both referral processes and adherence to standard guidelines in the treatment of prostate cancer patients.
Eradication of p53-mutated head and neck squamous cell carcinoma (HNSCC) xenografts using nonviral p53 gene therapy and photochemical internalisation (PCI)
Authors: A. Ndoye, G. Dolivet, A. Leroux, A. Hogset, P. Erbacher, K. Berg, J.-P. Behr, F. Guillemin, J. L. Merlin
Journal: Journal of Clinical Oncology (2005)

3155 Background: p53 gene therapy trials have been initiated using viral vectors in p53-mutated HNSCC. Alternatively, using nonviral vectors for gene therapy is limited because of their low transfection rate. Our in vitro results using PCI demonstrated that PCI enhances the transfection efficiency of polyethylenimine-mediated p53 gene transfer and justify in vivo evaluation. Methods: Tetraglucosylated polyethylenimine (PEIGlu4)-mediated gene transfer was performed alone or in conjunction with PCI, in mice bearing HNSCC xenograft. Using luciferase as reporter, we evaluate the influence of PCI on the transgene expression kinetics. Then, p53 gene transfer was performed by weekly injection of p53/PEIGlu4 complexes during five (Group A) or seven (Group B) consecutive weeks. Efficiency of the gene therapy was evaluated by following tumor growth and by analysis of P53, P21, mdm2, Bax and Bcl2 proteins expression. Results: Using PCI, the expression of luciferase was significantly (P < 0.01) enhanced. Enhancement was maximal (20-fold) at 48h and remained significant during 7 days after completion of the transfection protocol. Applying PCI to p53 gene transfer, tumor growth inhibition was observed in all transfected animals. One week after the last PCI-mediated p53 gene transfer, complete tumor regression was achieved in 4/6 mice (Group A) and in 6/6 mice (Group B). Three weeks after the transfection tumor regrowth was observed in 3/4 mice (Group A) and in 1/6 mice (Group B). Successful tumor cure was achieved in 1 mouse (Group A) and in 5/6 mice (Group B) that were still tumor-free 8 weeks after the last transfection. The use of PCI led to higher P53 protein expression and was correlated with subsequent induction of Bax, P21 and MDM2 proteins and with repression of Bcl2 protein. Conclusions: PCI enhances the in vivo efficiency of PEIGlu4-mediated p53 nonviral gene transfer and can be proposed as a potent alternative for p53 gene therapy in HNSCC. No significant financial relationships to disclose.
A phase II study of R-COMP14 in elderly patients with high-risk diffuse large B-cell lymphoma (DLBCL) and moderate to high “life threat” impact cardiopathy.
Authors: G. Corazzelli, F. Frigeri, M. Arcamone, A. Lucania, G. Capobianco, M. R. Villa, F. Russo, S. Crisci, G. Marcacci, C. Becchimanzi, E. Morelli, F. Volzone, R. De Filippi, A. Pinto
Journal: Journal of Clinical Oncology (2011)

8058 Background: R-CHOP14 delivery in pts with poor IPI score and/or EBV+ and cardiac morbidity, may be hampered by acute, early and late cardiac toxicity from dose-dense doxorubicin. Non-pegylated liposome-encapsulated doxorubicin (NPLD) is accounted as equivalent to free doxorubicin with less cardiac adverse events (CAE). Methods: Untreated pts (median age 73 y, r 62-82) with IPI 3-5 DLBCL and moderate-high ‘life threat’ impact cardiac comorbidity [lymphoma-validated NIA/NCI index (Janssen-Heijnen 2005)], entered a phase II study of 6 biweekly courses of R-COMP14 (R-CHOP with doxo replaced by 50 mg/m2 of NPLD; Myocet). Therapy was given as inpatients with close cardiac monitoring. A CrCl >30 ml/min and left ventricular ejection fraction (LVEF) ≥0.45 were required. Age-adjusted Charlson Comorbidity Index (aaCCI) was used to weight comorbidity. Results: 41 pts were enrolled and 208 courses delivered at a median interval of 15.6 days (r 13-29); 67% of pts received all 6 courses. ORR was 73 %, with 68% CRs and 72% of 4y-DFS. Time to treatment failure (TTF) was 49% at 4 y (95% CI, 33-65%, median 19.2 mo.s). At a median of 27 mo.s, 20 failures occurred: 3 early deaths [day +12 (undefined) and +13 (sepsis), 1st cycle; day +18 (sepsis), 2nd cycle]; 8 therapy discontinuations due to no-response (n=2) and toxicity (n=6) [widespread zooster (n=1), CTCAE v3.0 G3 decrease in LFEV (n=3) and G3 arrhythmia (n=2)]; 6 relapses; 3 deaths in cCR due to cyrrhosis (n=1) and late CAE (n=2). Cumulative incidence of CAE-related failures was 7/41 (17%, 95% CI: 8-31%). AaCCI correlated with failures (P= 0.007) and pts with score ≤ 7 had a longer survival (66% vs 29%; P = 0.009). Time to progression (TTP) at 4 y was 77%; 4 CRs (TTP: 12, 16, 20+, 29+ mo.s) and 2 PRs (TTP: 8 and 14 mo.s) were registered among pts discontinuing treatment for toxicity. The estimated 4-y OS was 67%. Conclusions: R-COMP14 ensures a 'curative' strategy with high DFS to high risk elderly pts who would have been denied active treatment due to cardiac morbidity. Early occurrence of CAE, irrespective of total NPLD dose, dictates a close cardiac monitoring and/or shorter therapy. The aaCCI score predicts treatment failure due to CAE and early death.
The ATOM trial: A multicenter, randomized phase II study of modified FOLFOX6 plus bevacizumab and modified FOLFOX6 plus cetuximab for colorectal cancer with liver-limited metastases.
Authors: Yasunori Emi, Kei Muro, Takeharu Yamanaka, Yu Katayose, Hiroyuki Uetake, Kenichi Sugihara, Yoshihiro Kakeji, Michiaki Unno, Ichinosuke Hyodo, Naohiro Tomita, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2016)

TPS777 Background: It remains unresolved which antibody, anti-vascular endothelial growth factor or anti-epidermal growth factor receptor antibody, is the best targeted agent to combine with chemotherapy for patients having liver-limited metastases of KRAS Exon 2 or RAS wild-type colorectal cancer. Methods: The ATOM trial is a Japanese multicenter, randomized phase II study comparing modified FOLFOX6 plus bevacizumab with modified FOLFOX6 plus cetuximab in patients with unsuitable liver metastases for resection (5 or more liver metastatic lesions and/or maximum tumor diameter &gt; 5cm). Patients are enrolled and randomly assigned to receive either treatment in 1:1 ratio from May 2013 to April 2016. Stratification factors for randomization are synchronous or metachronous liver metastases, number (1–4 or ≥ 5) and size ( ≤ 5 cm or &gt; 5 cm) of metastatic lesions, and adjuvant chemotherapy with or without oxaliplatin-containing regimen. All patients are to be followed up to March 2017. Primary endpoint is progression-free survival (PFS). We employed a selection design based on hazard ratios. Planned sample size is 120 patients with 84 estimated PFS events based on the hypothesis to select the superior treatment with the 75.0 % selection probability if the difference of both treatments is a 1-year PFS rate of 5% and the inferior treatment has a 1-year PFS rate of 50%. Secondary endpoints are response rate, tumor shrinkage at week 8, liver resection rate, time to treatment failure, overall survival, quality of life, and adverse events. Exploratory endpoints include pathologic and morphologic assessments, which will be investigated in collaboration with radiologists and pathologists. The plasma factors relating to tumor angiogenesis are assessed sequentially to explore the association with treatment efficacies. As of Aug 20 th 2015, 102 patients were enrolled. The results from this trial will show which targeted agents should be used to treat liver-limited diseases from colorectal cancer with WT RAS tumor. Clinical trial information: NCT01836653.
Improving patient selection for oncology phase I trials: Predictors of 90-day mortality and overall survival.
Authors: N. G. Chau, A. Florescu, K. K. Chan, L. Wang, E. X. Chen, A. M. Oza, L. L. Siu
Journal: Journal of Clinical Oncology (2010)

2588 Background: Phase I trials are critical for the development of new therapies in oncology. Typical inclusion criterion for phase I trial entry includes life expectancy > 3 months to ensure appropriate patient selection; however 90 day mortality (90DM) and overall survival (OS) are difficult to predict. Methods: We analyzed 233 consecutive solid tumor patients (pts) who were treated in one of 30 phase I trials (38% targeted agents alone, 58% targeted agent plus chemotherapy) from Jan 06 to Jul 09 at Princess Margaret Hospital. We assessed the relationship between 17 clinical characteristics and 90DM using univariate and multivariate logistic regression analyses to create a risk score (PMHI). We also applied the Royal Marsden risk score (RMI), which is based on 3 objective baseline markers (albumin <35g/L, >2 metastatic sites, LDH >ULN) (Arkenau et al. JCO 2009). Both PMHI and RMI are assessed for their predictability of 90DM and OS in our cohort. Results: Median age was 57 yrs (range 21-88), M:F (%) = 53:47, ECOG 0:1:2 (%) = 45:52:3, median number of prior lines of systemic therapy = 2 (range 0-14), number of metastatic sites 0:1-2:>2(%) = 9:59:32. Median follow-up time = 224 days (range 23-1,345). Thirty-three pts died within 90 days of starting treatment; hence 90DM = 14%; median OS = 320 days (95% CI 270-365). The PMHI consists of 3 factors (albumin <35g/L, >2 metastatic sites, ECOG PS >0), which differs from RMI by 1 factor (ECOG vs. LDH). For 90DM, PMHI had a higher area under ROC curve value (0.782) compared to the RMI (0.696) (p=0.02). For OS, RMI appears to be slightly more predictive than PMHI. Conclusions: To predict life expectancy <90 days, risk models should include ECOG PS>0. LDH, which reflects tumor burden, is not predictive of 90DM, but did predict of OS in our cohort, which consists largely of pts with good ECOG. To predict overall survival, risk models using objective baseline laboratory and radiological assessments are helpful. Multivariate analysis Risk score 90DM (OR; 95% CI; p value) OS (HR; 95% CI; p value) PMHI (albumin, metastatic sites, ECOG) ≥ 2 7.2 (2.9-18.0), p < 0.0001 1.6 (1.0-2.5), p = 0.046 RMI (albumin, metastatic sites, LDH) ≥ 2 1.1 (0.4-2.9), p = 0.87 2.2 (1.3-3.6), p = 0.002 No significant financial relationships to disclose.
Influenza (flu) Vaccine Administration to Patients with Multiple Myeloma (MM) Prior to Autologous T-Cell Harvest Leads to Better Reconstitution of Flu Immunity After High Dose Melphalan and Autologous Stem Cell Transplant (ASCT) and Reinfusion of Primed Ex-Vivo Co-Stimulated Autologous T-Cells and Post-ASCT Second Flu Vaccination Than Post-ASCT Flu Vaccination Alone.
Authors: Edward A. Stadtmauer, Dan T. Vogl, Nicole A. Aqui, Aaron P. Rapoport, Kenyetta Macdonald, Heather Murphy, Rita Bhagat, Patricia A. Mangan, Anne Chew, Elizabeth Veloso, Bruce Levine, Robert H. Vonderheide, Carl H. June, Kathleen Sullivan
Journal: Blood (2009)
Impact of direct physician-to-physician contact on accelerating oncology clinical trial accrual in multiple tumor types.
Authors: J. R. Eckardt, A. W. DeMaggio, O. Peracha, A. Nemeth, S. Sarvepalli, M. Levonyak, N. Ku
Journal: Journal of Clinical Oncology (2011)

e13039 Background: Only 3-5% of new cancer pts participate in clinical trials, often resulting in prolonged trial completion timelines, and delays in the availability of effective treatment to pts. Barriers to pt accrual include physician awareness and attitudes, access to protocols, administrative burdens to conduct clinical trials, cost to physicians and pts, and pt concerns about participation in research trials. To overcome these barriers, DAVA Oncology has initiated strategies to improve clinical trial accrual that optimizes trial enrollment and engagement through a direct physician to physician intervention. Methods: Participating investigators are segmented into key performance categories that allow tactics to be tailored based upon the relative potential impact of each site to the trial. DAVA Medical Oncologists then engage with PIs using information such as customized enrollment plans that provide historical performance, site specific screening and enrollment challenges, and patient flow schematics. Key treatment specialists are targeted for trial education and engagement. Results: The implementation of direct physician-to-physician intervention resulted in a measurable improvement in the monthly accrual to each of 7 oncology trials. In two phase III studies, enrollment increased 16.3% per site/month during an 18 month engagement, and 27.7% during a 12 month engagement, respectively. Conclusions: The use of site specific strategies based upon performance potential, enrollment challenges and patient flow, tactically implemented by direct physician to physician contact, has been successful in significantly accelerating clinical trial accrual in 7 trials initiated to date. Accrual enhancement. Trial Accrual before* Accrual after* % Increase 1 0.11 0.14 27.7 2 0.23 0.27 16.3 * Patients per site per month.
The impact of the multiple types of treatments on OS and the decline of liver function in patients with advanced stage of HCC.
Authors: Petra Prins, Prarthna Bhardwaj, Thomas Fishbein, Lynt B. Johnson, Coleman Smith, Rohits Satoskar, Alexander Y. Kim, Reena Jha, Hongkun Wang, David Sullivan, Salha Taher, Tiger Zhang, J Zhu, Michael J. Pishvaian, Brandon George Smaglo, Mohamed E. Salem, Marion L. Hartley, John Marshall, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2016)

461 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death worldwide. Most HCCs develop in severely damaged liver. Methods: The effect of multiple treatment options on liver function (LF) and disease outcome of patients (pts) with HCC (n = 185) were examined retrospectively. Pt tumor burden (using Barcelona clinic liver cancer [BCLC] classification) and LF (Child Pugh [CP]) were assessed at time of diagnosis and then after treatment. Using Kaplan Meier with log rank and T tests, BCLC and CP scores were correlated with overall survival (OS) following individual treatment regimens. Results: We show that better BCLC and LF scores at time of diagnosis predict a better outcome (median OS; p &lt; 0.05). Pts received one or more of the following: no treatment, experimental treatment, TACE, Y90 radioembolization, radiofrequency ablation, resection, radiation, and sorafenib (SFB). Considering all treatment scenarios, LF improved in 9.5%, did not change in 33%, and worsened in 57% of pts. Sixty percent of untreated pts experienced LF decline, compared with 33, 54, 48 and 50% of pts receiving TACE, SFB, TACE/SFB, and Y90/SFB, respectively (no significant differences [NS]); 72% of pts receiving TACE/Y90/SFB (NS); and 85% of pts receiving other Y90/SFB combinations (p = 0.006). In general, pts who saw no change or an improvement in LF from baseline had longer median OS versus pts who had declining LF (p &lt; 0.002). However, pts receiving TACE/Y90/SFB (n = 29) had similar OS to those receiving TACE/SFB (n = 35), despite the toxicity difference (72% [TACE/Y90/SFB] vs. 48% [TACE/SFB] of pts had declining LF). TACE/SFB or TACE/Y90/SFB led to longer median OS than any other treatment group (p = 0.017). Conclusions: The outcome of pts with HCC depends on disease stage and LF. Most pts experience LF decline during treatment. Despite LF decline in 48% of pts receiving a SFB/TACE, these pts experienced longer median OS than pts on any other treatment. Balancing survival benefit with liver toxicities is critical to the successful treatment of pts with advanced HCC. Agents with good antitumor activity and minimal liver toxicity are desperately needed for these pts.