tbuckley/cabot-search huggingface dataset:
Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC)
Authors: I. Malik, J. R. Hecht, A. Patnaik, A. Venook, J. Berlin, G. Croghan, L. Navale, M. MacDonald, S. Jerian, N. J. Meropol
Journal: Journal of Clinical Oncology (2005)

3520 Background: Panitumumab (formerly ABX-EGF) is a fully human monoclonal antibody that binds with high affinity to the epidermal growth factor receptor (EGFr). This ongoing phase 2 study is evaluating the safety and efficacy of panitumumab monotherapy in patients (pts) with mCRC who have failed standard chemotherapy. Here we present mature unaudited data from the ongoing study. Methods: Pts with mCRC who failed therapy with a fluoropyrimidine (± leucovorin) and either irinotecan or oxaliplatin, or both, were eligible for this study. Cohort A included pts with EGFr staining of 2+ or 3+ in ≥ 10% tumor cells; cohort B included pts with EGFr staining of the sum of 1+, 2+ and 3+ in ≥ 10% of tumor cells, but with the sum of 2+ and 3+ in < 10% of tumor cells. Panitumumab was given IV at 2.5 mg/kg once weekly in 8-wk cycles. Pts continued receiving treatment until disease progression or unacceptable toxicity occurred. Endpoints included tumor response (RECIST), time to disease progression, survival, and safety. Results: Enrollment is complete, with treatment ongoing. In total, 148 pts were treated (82 men/66 women; ECOG status of 1 [n = 111] or 0 [n = 37]; mean age 59 yrs [range 21 - 88 yrs]). Efficacy results are shown in the table. The 4 most frequently reported grade (gr) 3 or 4 treatment-related adverse events (AEs) were rash NOS (5 pts), fatigue (4 pts), vomiting NOS (2 pts), nausea (1 pt), and pruritus (1 pt). Skin toxicity-related AEs were reported for 141 pts (95%; 5% gr 3 and no gr 4). One infusion-related gr 3 AE, which did not require dose modification, was reported; no other infusion-related AE has been reported to date. No human anti-human antibodies were observed in 145 pts tested. Conclusions: These mature data confirm previously reported safety and response findings (Hecht et al, 2004) and provide encouraging survival data in pts with mCRC who have failed multiple lines of standard chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Genentech, Pfizer, Sanofi Amgen Amgen, Bristol-Myers Squibb, Genentech, Novartis, Pfizer, Roche Amgen, Eli Lilly, Pfizer, Roche Amgen
Clinical and pathologic factors associated with development of hepatocellular carcinoma in patients with hepatitis virus-related cirrhosis: A long-term follow-up study
Authors: D. Morales-Espinosa, A. Martínez-Velasco, T. Cerón-Lizárraga, V. Rosas-Camargo, J. L. Rodríguez-Díaz, D. Flores- Estrada, A. Gamboa-Domínguez, O. Arrieta
Journal: Journal of Clinical Oncology (2007)

4646 Background: Hepatocellular carcinoma (HCC) represents &gt;90% of primary liver neoplasms and develops mainly in patients with liver cirrhosis. Risk factor identification for development of HCC in patients with cirrhosis is of great relevance due to its high incidence and poor prognosis when detected at advanced stages. The aim of our study was to identify HCC development-associated risk factors in a cohort of patients with hepatitis virus-related chronic liver disease and cirrhosis. Materials and Methods: Patients with diagnosis of hepatitis virus-related cirrhosis from January 1980 to January 2000 were included. Patients were followed with abdominal US and determination of AFP levels, physical examination, and biochemical tests every 3–6 months. The endpoint in this study was defined as development of HCC. Liver histology was evaluated according to the METAVIR. Results: 282 patients met the inclusion criteria; most (86%) had a serologic diagnosis of hepatitis C virus, and only 14% had hepatitis B virus at the time of diagnosis of cirrhosis, while 56 and 37% were classified as Child A and B, respectively; only 7% as Child C. Histological activity was mild in 59% of patients; moderate and severe in 41%. Mean annual incidence was 1.87%; 22 and 35% of patients developed HCC at 10 and 15 years of follow-up, respectively. Diagnosis of HCC was made by histopathology in 37% and by tumoral lesion-associated AFP elevation confirmed by imaging studies in 63%. In multivariate analysis, 3 variables were associated with HCC: moderate to severe histological activity; platelet count &lt;105 10 3 /mm 3 , and alpha- fetoprotein &gt;5 ng/mL. We divided patients into two groups according to regression coefficient: low and high-risk; patients assigned to the low-risk group showed 5, 10, and 15-year HCC incidences of 3.4, 6.4, and 6.4%, respectively, in contrast to patients from the high-risk group, who showed incidences of 17.8, 33.5, and 56.8%, respectively. Conclusions: We found three HCC-associated variables: histological activity; platelet count and alpha-fetoprotein levels. Patients considered as high-risk for developing hepatocellular carcinoma must be considered candidates for closer follow-up. No significant financial relationships to disclose.
Stanford V chemotherapy and involved field radiotherapy for children and adolescents with unfavorable risk Hodgkin lymphoma: Results of a multi-institutional prospective clinical trial.
Authors: Monika Metzger, Amy Billett, Alison M. Friedmann, Matthew J. Krasin, Scott C. Howard, Howard J. Weinstein, Eric Larsen, Karen Chayt Marcus, Catherine Billups, Jianrong Wu, Sarah S. Donaldson, Michael Paul Link, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2012)

9502 Background: To evaluate the efficacy of 12 weeks of Stanford V chemotherapy (prednisone, vinblastine, doxorubicine, nitrogen mustard, etoposide, vincristine, and bleomycin) without routine growth factor support plus response-adapted low-dose, involved-field radiotherapy (IFRT) in children and adolescents with unfavorable risk Hodgkin lymphoma (HL). Methods: Multi-institutional (St. Jude Children’s Research Hospital, Stanford University, Children’s Hospital Boston, Massachusetts General Hospital and Maine Children’s Hospital) clinical trial. One hundred forty-one patients with clinical stages IIB (n=43), IIIB (n=19), IVA (n=27), and IVB (n=52) HL were treated with 12 weeks of Stanford V chemotherapy and low dose IFRT between June 2002 and May 2011. Involved nodal sites in complete remission (CR, defined as &gt; 75% shrinkage of the original tumor and PET negative) after 8 weeks of Stanford V received 15 Gy IFRT; those sites that achieved only partial response received 25.5 Gy IFRT after completion of all 12 weeks of chemotherapy. Results: With a median follow-up of 4.6 years, the 3-year overall and event-free survival (EFS) are 97% (SE=2%) and 79% (SE=4%) respectively. There was no significant difference in EFS by stage (IIB vs. IIIB vs. IV; P=0.84). Ten patients developed progessive disease and 18 relapsed, while 5 have died (1 after relapse in an accident and 4 of refractory disease). Most common toxicities were grade 3 hematologic with 234 episodes of neutropenia in 101 patients (72%) and 85 episodes of anemia in 52 patients (37%); Fever and neutropenia occurred 13 times in 12 patients (9%). Conclusions: Risk-adapted, combined-modality therapy using 12 weeks of Stanford V chemotherapy plus IFRT is well tolerated in this population with manageable acute toxicities. Overall survival is comparable to other more intense chemotherapy regimens. Future high-risk front line therapies may consider a Stanford V backbone with targeted intensification and further tailoring of radiation therapy.
A genome-wide association study (GWAS) of docetaxel-induced peripheral neuropathy in CALGB 90401 (Alliance).
Authors: Daniel Louis Hertz, Kouros Owzar, Susan Halabi, William Kevin Kelly, Hitoshi Zembutsu, Chen Jiang, Jai Narendra Patel, Dorothy Watson, Ivo Shterev, Deanna L. Kroetz, Paula N. Friedman, John Francis Mahoney, Michael Anthony Carducci, Michael J. Kelley, Eric Jay Small, Phillip G. Febbo, Yusuke Nakamura, Michiaki Kubo, Mark J. Ratain, Howard L. McLeod
Journal: Journal of Clinical Oncology (2013)

11053 Background: There are currently no effective methods for predicting, preventing, or treating chemotherapy-induced peripheral neuropathy. We performed a genome-wide association study in a clinical trial of castration-resistant prostate cancer (CRPC) to discover variants that may be useful for identifying patients at high risk of neuropathy during docetaxel treatment. Methods: Treatment and toxicity data were collected prospectively on the Cancer and Leukemia Group B (CALGB) 90401 trial of chemotherapy naïve CRPC patients treated with docetaxel and prednisone ± bevacizumab. Genotyping was performed by the RIKEN Institute using the Illumina HumanHap610-Quad platform. Genetically defined European subjects were included in the discovery analysis of all single nucleotide polymorphisms (SNPs) that passed quality control. The primary endpoint was the cumulative dose level triggering a grade 3+ sensory neuropathy. The inference was conducted within the framework of a competing risk model accounting for early treatment termination induced by death or progression, or other toxicities. SNPs that were highly associated with neuropathy were assessed for a broader taxane effect in a cohort of paclitaxel-treated patients from a breast cancer clinical trial, CALGB 40101. Results: 623 Caucasian patients and 498,022 SNPs were included in the discovery analysis. The incidence of grade 3 neuropathy was 8%. One intergenic SNP (rs11017056) was associated with increased risk of neuropathy (HR=2.83, p=4.7x10 -7 ). This association surpassed the genome-wide significance threshold after covariate adjustment (p=7.2x10 -8 ). However, none of the 7 SNPs selected for replication were associated with neuropathy in the paclitaxel-treated breast cancer cohort. Conclusions: Using a prospectively enrolled prostate cancer patient cohort we identified multiple SNPs that may identify risk of docetaxel-induced peripheral neuropathy, but not paclitaxel-induced neuropathy. However, since it is unknown whether the genetic factors that affect taxane neuropathy are drug-specific, further replication studies in docetaxel-treated cohorts are of great interest.
What is the yield of regional lymph node dissection following sentinel lymph node involvement in patients with breast cancer?
Authors: M. Ortega, M. Ruiz-Echarri, E. Prats, R. Lastra, E. Aguirre, J. Lambea, E. Milastre, J. Mayordomo, P. Razola, A. Tres, J. Banzo
Journal: Journal of Clinical Oncology (2006)

10782 Background: Sentinel lymph node is a minimally invasive and accurate staging procedure for patients with invasive breast cancer. Histological SLN involvement with cancer cells requires regional lymph node dissection. Aim: To verify if subgroups of patients with sentinel lymph node involvement in which the risk of histological involvement of additional regional lymph nodes is minimal can be identified. Methods: Ninety six consecutive patients with invasive breast cancer and tumour size less than two centimeters by mammography, had lymphoscintigraphy with colloidal 99Tc and radioisotope-guided sentinel lymph node biopsy in the University Hospital of Zaragoza from 1999 to 2005.Pathological assessment included serial sections of the sentinel lymph node with inmunohistochemistry for cytokeratins in selected cases.39 patients had histological involvement and are presented in this analysis. Results: All 39 patients were females. Median tumour size was 20 mm (range 5–52) Median number of resected sentinel lymph node was 2 (range 1–5) Median number of involved sentinel lymph node was 1 (range 1–4) Regional lymph node dissection was performed in all patients (Axillary dissection in 31; internal mammary dissection in 1, both in 7). Median number of nodes was 13 (range 2–34) At least 1 additional involved lymph node was found in 19 patients (48%) We have correlated patient age, menopausal status, pathological tumour size, histological grade, estrogen receptors, progesterone receptors and Her2 with the risk of histological lymph node involvement in regional lymph node dissection. Conclusions: Tumour size was significantly associated to such risk: No significant financial relationships to disclose.
Terminal phase in patients (pts) with advanced sarcomas: A perspective study for a better assistance
Authors: A. Comandone, C. Oliva, A. Boglione, F. Garetto, P. Bergnolo, O. Dal Canton, S. Chiado Cutin, P. Pochettino, G. Gino, E. Brach Del Prever
Journal: Journal of Clinical Oncology (2006)

9551 Background: Sarcoma are rare tumors, with an incidence &lt;1% of all neoplasms. Very few data are available on the clinical and psychological needs of the pts in terminal phase of these diseases. In terminal phase the goal is no more cure or prolongation of life, but the control of symptoms related to the disease progression. Methods: As a specialized interdisciplinary group we have started to treat the pts afflicted from soft tissue and bone sarcomas since 1994. We have recorded in a perspective study the problems of the terminal pts from 1998 until 2005. We have followed 178 pts with sarcomas in terminal phase for at least 3 months: 95 males and 83 females, median age 57 years, median PS 50 Karnofsky. Histologically 143 had soft tissue sarcomas, 28 osteosarcomas, 7 Ewing sarcomas. Extremities were the origin of the disease in 33.7% of the cases, abdomen in 29.2%, trunk in 21.9% and other sites in 15.2%. Site of recorded metastases: lung 48.3%, liver 18.5%, bone 15.7%, brain 7.9%, nodes 4.5%. Inoperable primary tumors or local relapse 30.9%. Results: During the last part (1 months) of their lives the pts complained with: pain 78.7%, dyspnoea 48.9%, anxiety 16.9%, gastrointestinal obstruction 24.7%, anorexia 51.1%, bleeding 7.9%. 57.3% of these pts died at home, 42.7% at the hospital. To control pain, dyspnoea and the other symptoms radiotherapy (43%), supportive care (100%) and palliative chemotherapy (36%) were used. Psycological support was offered to the majority of pts (63.5%) as well as physical rehabilitation (56.8%). Conclusions: Supportive care of pts with advanced sarcomas is an underestimated aspect in clinical oncology. We have demonstrated that these pts have specific needs, on some aspects, different from those of the pts afflicted from the most common cancers. A complex, multidisciplinary approach is necessary in order to improve the assistance and quality of life of these pts. No significant financial relationships to disclose.
Adequate lymph node assessment for extrahepatic bile duct cancer: Do the data support the current AJCC recommendations?
Authors: K. Ito, H. Ito, M. Gonen, P. J. Allen, M. I. D’Angelica, Y. Fong, R. P. DeMatteo, L. H. Blumgart, W. R. Jarnagin
Journal: Journal of Clinical Oncology (2009)

4576 Background: AJCC staging manual 6 th edition states that histologic examination of at least 3 lymph nodes (LN) is required for adequate N stage determination for extrahepatic bile duct cancer (EHBDCA). We hypothesize that this recommendation is insufficient and will lead to underestimation of N stage of EHBDCA. Methods: 257 patients (144 hilar [HCCA] and 113 distal [DCA] cholangiocarcinoma) who underwent curative intent resection for EHBDCA at our institution (1993 -2007) were analyzed. Final disease staging, including lymph node status and total number of nodes examined, was obtained from the pathology report. Differences in disease specific survival (DSS), according to nodal status, were compared using log rank test. R1 resections (n=51) were excluded from this analysis. Results: There were 89 patients (34.6%) with LN metastasis. On multivariate analysis, LN metastasis was an independent prognostic factor of poor survival (median DSS N0 vs N1: 53.3 months vs 19.3 months, p&lt;0.0001, HR= 2.2 [95%CI: 1.5 - 3.2]). Median total LN count (TLNC) was 6 (range: 0 - 42). There was a significant difference in TLNC between HCCA and DCA (median = 3 [range: 0 - 16] vs 12 [range: 1 - 42], p&lt;0.001, respectively). Among patients who underwent R0 resection for EHBDCA, “N0” based on TLNC &lt; 11 was associated with worse DSS than “N0” based on TLNC &gt; 11. When analyzed separately, “N0” based on TLNC &lt; 7 for HCCA and &lt; 11 for DCA revealed poorer DSS than “N0” based on greater TLNC ( Table ). Conclusions: The recommendation for LN assessment of EHBDCA by AJCC 6 th Edition (“at least 3”) could lead the underestimation of N stage. HCCA and DCA should have separate recommendations for adequate LN assessment. [Table: see text] No significant financial relationships to disclose.
A phase I study of XL184, a RET, VEGFR2, and MET kinase inhibitor, in patients (pts) with advanced malignancies, including pts with medullary thyroid cancer (MTC)
Authors: R. Salgia, S. Sherman, D. S. Hong, C. S. Ng, J. Frye, L. Janisch, M. J. Ratain, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

3522 Background: XL184 is an orally bioavailable inhibitor of RET, MET & VEGFR2. XL184 strongly inhibits cell proliferation in MTC cell lines harboring activated RET, & pharmacodynamic studies showed substantial inhibition of RET & MET phosphorylation in TT (MTC model) xenograft tumors. Methods: Pts received XL184 QD on Days (d) 1–5 of each 14 d cycle (5&9 schedule), or continuous QD dosing. Dosing changed from mg/kg (Cohorts [C] 1–9) to flat dosing in C10. The formulation changed from suspension to capsules in C12. Response, PK & pharmacodynamic parameters are assessed. Results: 55 pts (13 w/MTC) have been treated at 13 dose levels: 0.08 - 11.52 mg/kg, 5&9 (C1–9); 175 mg/d (C10), 265 mg/d (C11), 175 mg/d (C12), & 250 mg/d (C13). 6 DLTs include 1 report each of grade (G) 3 palmar/plantar erythema, & G 3 AST, ALT & lipase elevations at 11.52 mg/kg 5&9, and G 2 & 3 mucositis at 265 mg/d resulting in dose reduction. Prominent non-DLT toxicities include diarrhea & hypopigmentation of the hair. As of 12/3/2007, 27 of 45 pts (60%) had no XL184-related toxicity > G1. PK analysis suggests linear PK; the terminal half-life is 59–136 hrs. Analysis of plasma samples showed a trend toward increased VEGF-A & PlGF & slightly reduced sVEGFR2 levels. 22 pts have had SD ≥ 3 M including 12 pts w/SD ≥ 6 M. 3 pts w/MTC had a confirmed PR (PRc) & 1 pt w/neuroendocrine carcinoma had an unconfirmed PR. All evaluated pts w/MTC had reductions in plasma calcitonin & CEA. Data for pts w/MTC are reported in the following table: Conclusions: XL184 is generally well tolerated & dose escalation continues. The MTD cohort will be expanded to include ≥ 20 pts w/MTC. Anti-tumor activity has been observed in pts w/various cancers, including MTC. Data for Pts w/ MTC Pt # 1 2 3 4 5 6 7 8 9 10 11 12 13 Months on Study 17+ 14+ 10 11+ 6+ 4+ 4+ 3+ 3+ 3+ 1+ <1+ <1+ Tumor Measurements a -22 -39 NM -48 - 12 -16 -30 -14 NM 0 TEE TEE TEE Best Response SD PRc SD PRc SD SD PRc SD SD SD TEE TEE TEE Activating RET Mutation + NA + + + NA NA + + NA NA NA NA Calcitonin a -81 -96 -91 -89 - 52 -78 -83 -88 -50 -52 NA NA NA CEA a -42 -85 -51 -69 - 5 -16 -37 -19 -22 NA NA NA NA a % change from baseline was rounded to the nearest integer. NM, Non-measurable disease; TEE, too early to evaluate; NA, not available Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Exelixis Exelixis Exelixis Exelixis
Late term renal complications related to chemoradiotherapy in patients with gastric cancer
Authors: A. Mayadagli, O. O. Seseogullari, C. Gemici, A. Ozkan, C. Parlak, E. Gocen
Journal: Journal of Clinical Oncology (2007)

15033 Background: The aim of this study is to evaluate late term renal complications of the combined treatment with chemoradiotherapy, according to the scheme of McDonald et al, in patients diagnosed with gastric cancer, after radical curative surgery. Methods: Totally 44 patients who administered to our clinic between years 2003 and 2004, with the diagnosis of gastric cancer, and with the age-adjusted creatinine clearance test (CCT) results within normal range, were enrolled into the study. Surgical procedure was subtotal gastrectomy in 34 patients (63,6%), and total gastrectomy in 16 patients (36,4%). Total 4600 cGy radiotherapy was administered to all patients through parallel-opposed AP-PA fields in 23 fractions concomitant with chemotherapy according to the scheme of McDonald et al. One year after the completion of the treatment, a technetium 99-m renal scintigraphy (DMSA) and CCT were performed to all patients whose renal functions were within normal limits. Results: Median age in the study was 52 (22–78). 34 patients (77,3%) were male and 10 (22,7%) were female. TNM stages were stage II in 15 (34,1%), IIIA in 21 (47,7%), IIIB in 4 (9,1%), and IV in 4 cases (9,1%). CCT measured 1 year after the treatment was low in 13 patients (29,6%), and within normal range in 31 patients (70,4%). Renal scintigraphy revealed damage at one pole in 32 patients (72,7%), damage at bilateral renal poles in 8 patients (18,3%), and it was normal in 4 patients (9%). Renal damage was higher in left kidneys than right kidneys (89,9% vs. 15,4%). There was a correlation between CCT values and scintigraphical findings. Damage in bilateral renal poles was higher in cases with low CCT than in cases with normal values (85,7% vs. 15,4). In general, there were no statistically significant relationship between late term renal complications and sex, and grade III treatment-related gastrointestinal toxicity. However, the relationships with age, extent of surgery reached statistical significance (p=0.009, and =0.006). Renal damage was notably higher in older patients, and in patients who underwent total gastrectomy. Conclusions: Since postoperative chemoradiotherapy is a novel modality for the treatment of gastric cancer, more studies are required in order to evaluate chronic toxicities. No significant financial relationships to disclose.
Gemcitabine plus cisplatin in pretreated metastatic breast cancer.
Authors: G. L. Moura
Journal: Journal of Clinical Oncology (2010)

1118 Background: Synergistic action of gemcitabine and cisplatin combination as well as its noncross resistence profile with taxane and anthracyclines have been explored in metastatic breast cancer. Many schedules and doses have been tested. This study examined the response rate, response duration, toxicity, and overal survival of gemcitabine and cisplatin in pretreated metastatic breast cancer. Methods: From June 2002 to November 2007, 97 patients with metastatic breast cancer were treated. Eligible patients had to have measureble disease and no more than four prior CT lines. All patients had received taxanes or anthracyclines. There were 42 HR-negative patients (43%) and 55 HR-positive (67%) patients. The treatment consisted of gemcitabine 700mg/m2 plus cisplatin 30 mg/m2 given on d1 and d8 every 3 weeks. A median of nine cycles was delivered. Median age was 51 years (range 31-72). Results: The overal response rate was 35% (95% CI, 24%-46%). Duration of response was 7.8 months (range 4.3-11.3). The median overal survival was 8 months (95% CI, 5-11). The response rate for HR-negative patients was 67% and OS 14 months (95% CI 9-18) compared to 33% for thr HR-positive patients. Toxicities grade 3 were thrombocytopenia 42% and neutopenia 32%. Nausea and vomiting (39%), neuropathy (34%), and asthenia (32%) were grade 2. There were no treatment-related deaths. Conclusions: For patients with metastatic breast cancer already exposed to taxane and anthracyclines and HR-negative tumors gemcitabine and cisplatin may offer better response than HR-positive patients. Recent findings suggest that in HR-negative patients respond better when the combination is addded before several other regimes and may became more resintent when added latter. The sample size and the lack off comparative study does not permit any further conclusion. No significant financial relationships to disclose.