tbuckley/cabot-search huggingface dataset:
A phase I/II study of nintedanib and capecitabine in refractory metastatic colorectal cancer.
Authors: Patrick McKay Boland, Marwan Fakih, Kristopher Attwood, Melissa Robins, Renuka V. Iyer, Wen Wee Ma
Journal: Journal of Clinical Oncology (2017)

759 Background: Refractory metastatic colorectal cancer patients (mCRC) have a poor prognosis with median survival of 4-6 months. Nintedanib is a TKI which inhibits VEGFR, PDGFR, and FGFR with preclinical efficacy in bevacizumab resistant CRC. This phase I/II study sought to evaluate the recommended phase II dose (RP2D) and efficacy of nintedanib and capecitabine in refractory mCRC patients. Methods: Key eligibility criteria included histologically proven mCRC, ECOG PS of 0 or 1, progression/intolerance to a fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR therapy for RAS wt patients. Prior regorafenib, uncontrolled hypertension ( ≥ 160/90), recent clinically significant thrombosis/hemorrhage, or prior intolerance to capecitabine were exclusionary. Doses were escalated across 2 planned dose levels (DL) in a standard 3+3 design, with escalating doses of capecitabine. DLT observation window was the first 3 weeks after dosing. The primary endpoint was establishment of the RP2D. Results: 10 patients were enrolled across 2 dose levels. 1 patient withdrew consent and was replaced. 5 (50%) were PS 0. No grade 4 or 5 AEs were observed. No DLTs were observed. 2/10 (20%) of patients experienced a grade 3 AE, including hyperbilirubinemia (10%), AST elevation (10%), diarrhea (10%), dehydration (10%), and weakness (10%). The most common treatment-related AEs included palmar-plantar eythrodysesthesia (PPE) (50%), diarrhea (40%), stomatitis (30%), nausea (20%), vomiting (20%), and fatigue (20%). The RP2D was determined to be capecitabine 1000 mg/m2 divided bid and nintedanib 200 mg bid. PK data will be presented. Conclusions: Treatment was well tolerated. Most of the observed AEs were grade 1 or 2, without a marked difference between DLs. PPE was readily managed with dose adjustments. The phase II study is ongoing at the RP2D. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc. Clinical trial information: NCT02393755.
Long-term disease control of ≥2 years achieved with cabozantinib in subjects with metastatic medullary thyroid carcinoma on a phase I study.
Authors: Ezra E.W. Cohen, David S. Hong, David G. Pfister, Ravi Salgia, Barbara Burtness, Roger B. Cohen, Douglas Wilmot Ball, Ranee Mehra, Milan Mangeshkar, Yifah Yaron, Frauke Bentzien, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2013)

6090 Background: Metastatic medullary thyroid cancer (MTC) carries a median survival of about two years (Modigliani et al. 1998; Roman et al. 2006). Cabozantinib inhibits three primary pathways implicated in MTC pathogenesis and progression: MET, vascular endothelial growth factor receptor-2 (VEGFR2), and RET. A phase I study was initiated in September 2005 in patients (pts) with advanced solid tumors. Methods: 85 pts, including 37 with MTC were enrolled to evaluate safety, pharmacokinetics, and to determine maximum-tolerated dose (MTD). Once the MTD of 140 mg freebase (equivalent to 175 mg malate salt) was determined, 20 metastatic or locally advanced MTC pts were enrolled in an MTD expansion cohort. 10/37 MTC pts achieved a confirmed partial response (cPR) (Kurzock et al. 2011). We report here on long-term disease control (DC), defined as cPR or progression-free at ≥ 24 months (m), in the MTC cohort. Results: After a minimum follow-up period of 52 m, 11 of 37 pts (30%) experienced DC, and have remained progression-free for &gt; 24 m. Time from diagnosis and time since development of metastatic disease was similar in patients with (11) or without (26) long term DC. As of 04 Dec 2012, 5 of these 11 pts remain on treatment for a median time of 55 m (53-73m). A best response of cPR was associated with long-term benefit: 4/5 pts continuing on treatment achieved cPR, one achieved SD. The adverse event profile of cabozantinib was generally predictable and adverse events were managed with symptomatic treatment and dose modifications. The median final dose for pts with long-term DC was 60 mg (range 20-140), with a median number of dose reductions of 2 (range 0E4). Reasons for dose reductions in two or more pts experiencing long-term DC included diarrhea (7), palmar-plantar erythrodysaesthesia syndrome/rash (6), mucositis/stomatitis (3), anorexia (3), nausea (2), and vomiting (2). Conclusions: Treatment with cabozantinib demonstrates long-term DC in a cohort of pts with metastatic MTC. Cabozantinib offers an important new treatment option for patients with progressive, metastatic MTC. Clinical trial information: NCT00215605.
The humanistic burden of advanced non-small cell lung cancer on patients and their caregivers.
Authors: Gavin Taylor-Stokes, Robert Wood, Michael Lees, Bill Malcolm, Oana Chirita
Journal: Journal of Clinical Oncology (2017)

220 Background: A diagnosis of advanced non-small cell lung cancer (aNSCLC) presents significant physical, emotional and financial challenges for patients and their caregivers. This study provides insight into the humanistic burden on patients and their caregivers, as the disease progresses. Methods: Data were taken from a chart review and a cross-sectional study of a NSCLC patients and caregivers in France, Germany and Italy. Physicians provided data on patients’ age, sex, stage, line of therapy and ECOG (Eastern Cooperative Oncology Group) performance status (PS). The patient survey assessed the patients’ health state (EQ-5D), impact on work/activities (WPAI) and on quality of life (EORTC QLQ-C30). The caregiver survey included the WPAI and Zarit Burden Interview (ZBI). Patient and caregiver outcomes were stratified by the patients’ ECOG PS from 0 to 4 (best to worst status). Statistical significance was assessed using Kruskal-Wallis tests. Results: 1,030 patients completed the survey (mean (SD) age: 64.5 years (10.1), 65.9% male); the majority were stage IV (88.4%) and most (70.5%) were receiving 1 st line therapy. Caregiver forms were completed by 41.5% of patients’ caregivers; mean (SD) age: 53.5 years (12.5), 72.6% female; most were the patients’ partner (54.9%) or child (31.9%). In total, 19.4%, 43.5%, 27.4% and 9.7% of patients had a current ECOG PS of 0, 1, 2 or 3/4, respectively. All outcomes stratified by ECOG PS are reported below (all P &lt; 0.0001). Conclusions: As patients’ functionality deteriorates, so do their outcomes relating to health utility, impairment and quality of life. This deterioration also increases the burden on the caregiver. This study was sponsored by Bristol-Myers Squibb. [Table: see text]
Phase II randomized, placebo-controlled trial of phytotherapeutic product Catuama for breast cancer women undergoing adjuvant radiation therapy.
Authors: Felipe Melo Cruz, Daniel de Iracema Gomes Cubero, Patricia Xavier Santi, Luciana Garcia Landeiro, Andressa Sayuri Tamashiro, Larisse Soares Ribeiro, Auro Del Giglio
Journal: Journal of Clinical Oncology (2013)

e20524 Background: Fatigue and Depression are common in patients undergoing Breast Cancer (BC) treatment. Catuama is a registered phytotherapic that contains 4 brazilian herbs per capsule: Trichilia catigua (87.5mg), Ptychopetalum olacoides (87.5mg), Paullinia cupana (125 mg) and Zingiber officinale (10mg). Objectives: Since one of its constituents is Guarana (Paulinia cupana) which we already reported to have anti-fatigue effects, we decided to test Catuama potential anti-fatigue effects in BC women undergoing adjuvant 4 weeks of Radiation Therapy (RxT). Methods: This is a double blinded, randomized, placebo-controlled, Phase II cross-over trial. Patients with histologically proven BC with the indication of adjuvant RxT, non-pregnant nor breastfeeding, older than 18 years of age, with ECOG PS 0 or 1, without a history of cardiac, renal, hepatic or psychiatric decompensation, received Catuama 1 capsule twice daily versus a matching placebo for the first 2 weeks of RxT treatment, followed by a week of wash out, followed by an additional two weeks of treatment with crossover of experimental arms. Patients were evaluated on days 1, 15 and 36 with the Brief Fatigue Inventory (BFI), Hospital Anxiety and Depression Scale (HADS), Quality of Life FACIT-F, FACIT-ES questionnaires, and Chalder Fatigue scale. Results: We enrolled 90 patients with a median age of 53 years (26 – 80). We saw no statistically significant differences of FACIT ES, FACIT F, HADS, Chalder or BFI scores treated with Catuama or Placebo when we considered all included patients. When we selected only patients with a BFI score above 30, Catuama significantly decreased BFI scores as compared to baseline (p&lt;0.0001). We observed one instance of grade 3 hypermagnesemia in the Catuama arm and one patient had hyperglicemia grade 3 both in the Catuama and in the placebo arm. No grade 4 toxicities were seen. Conclusions: Catuama may help selected patients who already start RxT with evidence of fatigue.
Analysis of 94 patients with advanced biliary tract cancer
Authors: B. Andritzky, S. Adler, I. Burkholder, I. Thöm, G. Schuch, M. Görn, G. Schilling, L. Edler, C. Bokemeyer, E. Laack
Journal: Journal of Clinical Oncology (2007)

15172 Background: Cholangiocarcinoma or gallbladder cancer are often diagnosed at an advanced stage with limited treatment options. Methods: Between 1994 and 2004, 94 patients (pts) (47 male, 47 female) with advanced biliary tract cancer were treated at the Department of Oncology and Hematology, University Hospital Hamburg-Eppendorf. Clinical and histopathological characteristics, response to chemotherapy, and survival were investigated in a retrospective analysis. Median age was 59 years (range 30–80) and median Karnofsky performance status was 90%. Predominant histologic type was adenocarcinoma (94.7%). Primary tumor sites were extrahepatic bile duct (29.9%), gallbladder (28.7%), intrahepatic bile duct (10.6%), ampulla of Vater (2.1%), not specified (28.7%). Predominant localizations of metastases were liver (73 pts (77.7%)), lymph nodes (49 pts (52.1%)) and the peritoneum (14 pts (14.9%)). 33 pts (35.1%) underwent surgery of the primary tumor at time of diagnosis. Results: 72 of 94 pts (76.6%) received a first-line chemotherapy, all together 10 different chemotherapy regimens were used. The median number of cycles was 2.5 (range 1 - 12). A single agent chemotherapy with gemcitabine was the most often adminstered regimen (23 pts (31.9%)), followed by carboplatin and etoposide plus whole body hyperthermia (12 pts (16.7%)) and 5- fluorouracil and folic acid (10 pts (13.9%)). The overall response rate was 8.3% (95% CI 3.1 - 17.3) (34.7% SD, 47.2% PD, 9.7% not evaluable). Second-line chemotherapy was given in 27 patients, which induced no tumor response, but a stable disease rate of 22.2%. Median time to follow- up was 44.8 months. Survival was calculated for all 94 pts since time of diagnosis. Median overall survival was 12.2 months and median progression-free survival 9.2 months. The median overall survival time for the 72 pts who were treated with chemotherapy was 14.0 months, and for the 22 pts who did not receive chemotherapy 10.7 months (p=0.2). Conclusions: Our analysis showed a poor prognosis for patients with advanced biliary tract cancer. Response rate to chemotherapy was low. Therefore, well tolerated cytotoxic agents should be used and new treatment strategies (including molecular targeted therapy) should be further investigated. No significant financial relationships to disclose.
Clinical Outcomes from Androgen Signaling–directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302
Authors: Matthew R. Smith, Fred Saad, Dana E. Rathkopf, Peter F.A. Mulders, Johann S. de Bono, Eric J. Small, Neal D. Shore, Karim Fizazi, Thian Kheoh, Jinhui Li, Peter De Porre, Mary B. Todd, Margaret K. Yu, Charles J. Ryan
Journal: European Urology (2017)
Low-dose doxorubicin combined with trastuzumab in HER2-positive metastatic breast cancer: A single institution experience.
Authors: Elise de Savornin Lohman, Sabine C. Linn, Marleen Kok
Journal: Journal of Clinical Oncology (2014)

e11598 Background: Both anthracyclines and trastuzumab are highly effective in HER2-positive metastatic breast cancer (MBC) patients. However, trastuzumab is associated with an increased risk of cardiac dysfunction, especially in patients receiving concurrent anthracyclines. In MBC patients who have received multiple lines of chemotherapy, treatment with low-dose (LD) doxorubicin results in clinically significant disease control with only mild toxicity. Here we describe a single institution experience with the combined modality of LD-doxorubicin and trastuzumab, focussing especially on the cardiac safety profile. Methods: Retrospectively, we collected data of a consecutive series of 29 HER2-positive MBC patients who received weekly 10 or 15 mg (flat dose) LD-doxorubicin combined with trastuzumab (treated between 2008 and 2013). Progression-free-survival (PFS, defined as start of LD-doxorubicin with trastuzumab until treatment was ended because of progression or death), toxicity and cardiac adverse events were evaluated. Patients who were taken off treatment because of toxicity were censored. Results: Only 12 (41%) patients were pre-treated with an anthracycline-containing regimen in the adjuvant setting. For metastatic disease, patients had received 2 to 6 (with a mean of 3) lines of systemic therapy before starting LD-doxorubicin/trastuzumab. After one month of treatment, only 17% of the patients showed progressive disease. The median PFS was 2.8 months (range 0-14) with 8 (28%) patients with a PFS of 6 months or longer. No significant association between duration of PFS and previous lines of treatment or previous anthracycline-exposure was found. No grade 3 or 4 non-cardiac-toxicities were reported. Only two patients were diagnosed with congestive heart failure. Both patients had a history of major cardiovascular risk factors. Conclusions: This is the first report describing the combination of LD- doxorubicin and trastuzumab in extensively pre-treated HER2-positive MBC patients and results in disease control of longer than 6 months in 28% of patients with a low level of toxicity. Caution is warranted in patients with major cardiovascular risk factors.
Low-dose chemotherapy with methotrexate and vinblastine for Japanese patients with desmoid tumors: Relationship to CTNNB1 mutational status.
Authors: Yoshihiro Nishida, Satoshi Tsukushi, Hiroshi Urakawa, Shunsuke Hamada, Eiji Kozawa, Kunihiro Ikuta, Yuichi Ando, Naoki Ishiguro
Journal: Journal of Clinical Oncology (2015)

e21524 Background: Since 2003, meloxicam, which is a selective COX-2 inhibitor, has been applied consecutively as a first line treatment. Although not a few patients were resistant to this treatment, we applied low-dose chemotherapy following the treatment with meloxicam. This study was conducted to determine the efficacy and safety of low-dose chemotherapy with methotrexate and vinblastine for patients with desmoid tumors refractory to meloxicam treatment, particularly focusing on the relationship between efficacy and the status of CTNNB1 mutation status. Methods: Since 2003, patients diagnosed as desmoid tumors arising in extra-peritoneal regions, were consecutively and prospectively treated with meloxicam (10mg/day). Effects of meloxicam were evaluated with MRI and/or CT every 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST). Patients resistant to meloxicam treatment with inoperable tumors were subjected to low-dose chemotherapy composed of Methotrexate (MTX) (30mg/M2) and Vinblastine (VBL) (6mg/M2) every two weeks. Frozen specimens obtained at biopsy or formalin embedded tissues were subjected to the analyses for CTNNB1 mutation status. The factors correlated with efficacy of MTX + VBL treatment were analyzed including CTNNB1 mutational status. Results: Sixty-eight patients were prospectively treated with meloxicam. Among them, 15 patients received treatment with MTX + VBL. Among them, 7 patients showed a measurable response. Only one patient had disease progression. Seven tumors had 45A mutation in exon 3 of CTNNB1, 5 with 45F, and one with 45P and two with wild type. Clinical factors of gender, age, tumor size, treatment duration, number of cycles, and CTNNB1 mutational status did not correlate with the efficacy of MTX + VBL treatment. Few patients had grade 3-4 treatment related toxicity with biweekly treatment of MTX and VBL. Conclusions: Not a few patients revealed resistant to treatment with meloxicam. Every other week MTX and VBL treatment is well-tolerated and had favorable response for patients resistant to meloxicam treatment regardless of CTNNB1 mutational status.
Treatment of liver metastases in patients with neuroendocrine tumors: A National Comprehensive Cancer Network analysis.
Authors: Michael A. Choti, Sarah Bobiak, Mark Bloomston, Carrie C. Zornosa, Emily K. Bergsland, Jonathan R. Strosberg, Al Bowen Benson, Matthew Kulke, Manisha H. Shah, Eric K. Nakakura, James C. Yao
Journal: Journal of Clinical Oncology (2013)

4143 Background: The choice of therapy in patients with hepatic metastases from neuroendocrine tumors is controversial. The purpose of this study was to describe the utilization of liver resection and other locoregional therapies in the management of NET hepatic metastases in NCCN centers. Methods: The National Comprehensive Cancer Network (NCCN) Neuroendocrine Tumor Database tracks longitudinal care for patients treated at seven specialty cancer centers in the U.S. from 2004 to 2010. Patient and tumor characteristics, as well as the use of liver-directed therapy (LDT) in patients with neuroendocrine liver metastases (NELM) were evaluated. Results: Among 907 patients presenting with metastatic disease, 606 patients presenting with newly diagnosed disease or previously diagnosed disease with first distant recurrence of NELM were evaluated. LDT was used during some component of the patient care in only 43% of patients with NELM, the remainder received only systemic or no therapy. LDT varied by extent of disease (p=0.002) with a higher proportion of patients with liver-only disease receiving LDT (45%) compared to those with liver and extrahepatic disease (26%). There was a significant difference in LDT by functional tumor status (Χ 2 =6.84, p=0.03) and primary site of disease (Χ 2 =14.95, p=0.001) where a higher proportion of patients with hormonally functional tumors received LDT when compared to non-functional tumors (48% vs 42%) as well as those with primary small bowel carcinoid vs pancreatic NET (56% vs 39%). Among those treated with LDT, 39% underwent surgical resection, 57% intra-arterial therapy (IAT), and 4% ablation alone. Major hepatectomy was performed in 21%, multiple resections in 13%, and resection combined with ablation in 24% of patients receiving surgical therapy. Among the 147 patients treated with IAT, 52% received standard chemoembolization, 23% bland embolization, and 18% yttrium-90 therapy. Conclusions: Even at specialty centers less than half of patients received LDT, among which one-fifth had a hepatic resection. Future studies on this cohort will measure outcomes based on type of LDT.
Prognostic factors analysis of extraskeletal osteosarcoma: Updated results of an EMSOS study.
Authors: Alessandra Longhi, Andreas Leithner, Stefan S. Bielack, David Biau, Andreas Krieg, Frank Michael Klenke, Jose' Casanova, Craig Gerrand, Stefanie Hecker-Nolting, Gianni Bisogno, Cristina Ferrari, Alberto Righi, Stefano Ferrari
Journal: Journal of Clinical Oncology (2015)

10526 Background: Extra Skeletal Osteosarcoma (ESO) account 1% among soft tissue sarcomas. There is no agreement on the best strategy of treatment. Methods: An EMSOS collaborative study was performed and data of patients treated for an ESO at different EMSOS centers were collected. Results: 147 cases were evaluable. Median age was 53 years(13-84). There were 95 males, 52 females. 114 had localized disease and 32 were metastatic, 1 unknown. Median tumor size was 10 cm, median interval from symptoms onset to diagnosis was 4 months. Primary tumor site was lower limb in 73 patients , upper limb in 33 patients,12 were in viscera. 109/114 with localized disease had surgical resection of primary tumor , 80 had R0 resection, 23 R1, 6 unknown. Among 114 patients with localized disease 79 received chemotherapy: 61 received a bone osteosarcoma-like chemotherapy regimen and 12 a soft tissue sarcoma like regimen;6 unknown type . 34/114 patient with localized disease received RT. Median follow up for all patients was 30 months (1-384 ms), 87 patients were alive and 60 dead at last FUP; median follow up for 87 survivors patients was 51 ms (1-384ms).. 5yrs overall survival (OS) for all 147 was 55%, 62% for patients with localized disease and 28% for those with metastatic disease. Among 114 patients with localized disease, local relapse occurred in 29/114 (25%) , distant metastases in 41/114 (36%). In patients with localized disease the probability of 5-yr OS according to tumor and treatment variables is reported in the table below. Conclusions: 5yr OS and prognostic factors (age,size,margins,surgical remission) are similar to soft tissue sarcoma group. Only a positive trend was seen for chemotherapy at univariate analysis but not at multivariate analysis. 5-yr OS p-value Age 18-40 (23) 41-65 (59) > 65 (24) < 18 (8) 71% 67% 47% 47% 0.07 Size < 5cm (21) 5-10 cm (37) > 10cm (42) 89% 69% 42% 0.0007 Surgical CR Yes (100) No (13) 65% 37% 0.0006 Margins R0 (80) R1 (23) UK (6) 71% 57% 17% 0.003 Chemotherapy Yes(79) No (35) 69,5% 45% 0.05 Radiotherapy Yes (34) No (79) 62% 64% 0.8