tbuckley/cabot-search huggingface dataset:
Clinical characteristics associated with the development of anticipatory nausea and vomiting in cancer patients undergoing chemotherapy treatment.
Authors: G R Morrow
Journal: Journal of Clinical Oncology (1984)

Approximately one in four patients experiences nausea and/or vomiting in anticipation of a chemotherapy treatment by the time of their fourth treatment cycle. Anticipatory nausea and vomiting is a prevalent problem of clinical significance in the total management of chemotherapy side effects. While refractory to standard antiemetic treatment, anticipatory nausea and vomiting has been successfully treated with behavioral approaches such as systemic desensitization. The present study was designed to identify the characteristics of patients at high risk for developing anticipatory side effects. Early identification of cancer patients prone to developing anticipatory side effects could lead to preventive measures. One hundred seventy-six consecutive ambulatory patients with histologically confirmed cancer who were being treated at three geographically separate hospitals of the University of Rochester Cancer Center were studied at the time of their fourth chemotherapy treatment. Patients found to experience anticipatory nausea and vomiting were significantly more likely (P less than .001) to have four or more of the following characteristics than patients who did not report anticipatory side effects: (1) less than 50 years of age; (2) the experience of nausea and/or vomiting after their last chemotherapy treatment; (3) a description of nausea after the last treatment as "moderate, severe, or intolerable"; (4) a description of vomiting after the last treatment as "moderate, severe, or intolerable"; (5) the reporting of the side effect "warm or hot all over" after their last treatment; (6) a susceptibility to motion sickness; (7) the experience of "sweating after their last treatment"; (8) and the experience of "generalized weakness after their last chemotherapy treatment." Results support a view that anticipatory side effects are conditioned and point to practical interventions for their clinical control.
Dosimetric comparison of tangential beam radiotherapy of the chest wall in patients with breast cancer: IMRT versus 3DRT.
Authors: V. Rudat, A. A. Alaradi, A. Mohamed, J. M. Fitzpatrick, S. Tuwaijri, K. Al-Yahya
Journal: Journal of Clinical Oncology (2010)

e11087 Background: To evaluate whether tangential beam intensity modulated radiotherapy (IMRT) provides a better dose distribution to the planning target volume (PTV; chest wall) and organs at risk than standard tangential wedged three-dimensional radiotherapy (3DRT). Methods: For 20 subsequent breast cancer patients after mastectomy a 3D treatment plan and a tangential beam IMRT plan was generated for the adjuvant radiotherapy of the chest wall. The dose-volume histograms were evaluated for the PTV and organs at risk. Parameters of the dose distribution were compared using the two-sided paired student-t-test. Results: IMRT reduced significantly the percentage of tissue encompassed by the 95% isodose line (V 95%) of the ipsilateral lung from 6.3% to 2.6% (p < 0.01). Of the patients with left-sided breast cancer, the V95% of the heart was significantly reduced from 2.8% to 0.7% (p < 0.01). No significant difference of the dose distribution was found for the PTV. Conclusions: Tangential beam IMRT significantly reduced the volume of ipsilateral lung exposed to relatively high radiation dose and the volume of heart in patients with left-sided breast cancer. This might translate into reduced toxicity. No significant financial relationships to disclose.
Hepatic arterial infusion (HAI) of oxaliplatin plus intravenous (iv) fluorouracil (FU), leucovorin (LV), and cetuximab for first-line treatment of unresectable colorectal liver metastases (CRLM) (CHOICE): A multicenter phase II study.
Authors: D. Malka, E. Paris, C. Caramella, E. Boucher, R. Guimbaud, A. Celebic, T. De Baere, D. Elias, J. Pignon, M. Ducreux
Journal: Journal of Clinical Oncology (2010)

3558 Background: To determine the efficacy and tolerance of HAI oxaliplatin plus iv FU/LV and cetuximab in patients (pts) with unresectable CRLM. Methods: Main eligibility criteria for this phase II study (2-step Simon design) were: histologically proven colorectal adenocarcinoma; tumor wild-type KRAS status (protocol amendment in 09/2008); unresectable CRLM; no extrahepatic disease (except primary with absent/mild symptoms, and ≤ 3 nonspecific lung nodules ≤ 5 mm in diameter); no prior chemotherapy for metastatic disease; WHO performance status 0-1. After surgical or percutaneous insertion of an implantable HAI catheter, pts were treated with HAI oxaliplatin (100 mg/m2 in 2 hrs) plus iv modified LV5FU2 regimen (LV, 400 mg/m2 in 2 hrs; FU, 400 mg/m2 bolus then 2,400 mg/m2 in 46 hrs) every two weeks plus iv cetuximab (400 mg/m2 then 250 mg/m2/week, or 500 mg/m2 every two weeks) until disease progression, limiting toxicity, or resection. Primary endpoint was objective response rate (ORR) (RECIST). Secondary endpoints included toxicity (NCI CTC-AE v3.0), disease control rate (DCR), resectability rate, progression-free survival (PFS), and overall survival (OS). Results: A total of 36 pts were included in 6 centers from 11/2006 to 12/2009. Planned interim analysis on the 23 first pts (male, 61%; median age, 53 yrs [range, 33-75]) showed that most had extensive disease (≥ 4 CRLM, 86%; bilobar CRLM, 91%). Pts received a median of 10 cycles (range, 2-23). Main severe toxicity was peripheral neuropathy (61%), abdominal pain (52%), neutropenia (43%), and rash (30%). Among 21 evaluable pts, ORR was 90% (95%CI, 70-99; intent-to-treat ORR among the 23 pts, 83% [95%CI, 61- 95]) and DCR was 100% (95%CI, 84-100). Among the 23 pts, 11 (48%) underwent R0 resection and/or radiofrequency ablation. After a median follow-up of 11 months, median PFS was 20 months (median OS, not reached; 12- and 18-month OS, 100%). Conclusions: First-line HAI oxaliplatin plus iv LV5FU2 and cetuximab seems feasible and highly effective in pts with unresectable CRLM. Analysis on the whole pt population will be presented at the meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Amgen, Merck Serono, Novartis, Pfizer, Roche, sanofi-aventis Amgen, Merck Serono, Novartis, Pfizer, Roche, sanofi-aventis Merck Serono, Pfizer, Roche, sanofi-aventis Amgen, Roche
Operative morbidity following primary and interval debulking surgery for advanced ovarian cancer
Authors: P. G. Rose, S. Nerenston, M. F. Brady, D. Clarke-Pearson, G. Olt, S. C. Rubin, D. H. Moore, J. Small
Journal: Journal of Clinical Oncology (2004)

5010 Background: To compare the operative morbidity of primary (PDS) and interval debulking surgery (IDS) for advanced stage ovarian cancer. Methods: A large multi-institutional cooperative group study (GOG 152) was conducted to evaluate the impact of IDS on progression-free and overall survival. Operative records were reviewed to determine operative data and morbidity. The first three quartiles (1st q, median and 3rd q) of the distribution is reported. A sign test is used to compare the characteristics and morbidities between PDS and IDS. Results: Two hundred and one patients underwent IDS following randomization to this procedure and three cycles of chemotherapy. All but nine cases had PDS and all but one had IDS performed by a board certified GYN surgeon. The surgeon estimated a similar percentage of the initial tumor volume was debulked during PDS and IDS. However, significantly less ascites, blood loss and duration of hospitalization were reported with IDS. Conclusion: There is less operative morbidity with IDS than with primary debulking surgery. This is consistent with previous retrospective studies. A randomized trial evaluating the efficacy and morbidity of primary surgery vs neoadjuvant chemotherapy followed by IDS (EORTC 55971) is ongoing. No significant financial relationships to disclose.
Hepatitis B reactivation in an Irish dialysis unit, 2005
Authors: L Thornton, F Fitzpatrick, D de la Harpe, S Brennan, N Murphy, J Connell, H Humphreys, E Smyth, J J Walshe, M Crean, D O’ Flanagan
Journal: Eurosurveillance (2007)

In April 2005, a case of reactivation of hepatitis B virus (HBV) infection occurred in a patient undergoing haemodialysis in an Irish hospital. This incident potentially affected patients attending hospitals throughout the country, so a national incident team was set up coordinate the response to the incident. A total of 306 dialysis patients, attending 17 different dialysis centres (14 in Ireland), were identified as having been potentially exposed to HBV as a result of this incident. A programme of HBV serological testing and HBV vaccination was instituted. There was no evidence that any patient acquired HBV infection as a result of cross-infection from the index patient, although 11 patients (3.6%) had evidence of past infection (anti-HBc positive, HBsAg negative). The majority of patients in this cohort were of unknown HBV vaccination status (62.7%), 13.4% were fully vaccinated, 4.6% partially vaccinated and 15.7% unvaccinated. Of 239 tested for anti-HBs, 183 (76.6%) had a titre &lt;10 mIU/ml. Local incidents in dialysis units can have national implications due to the frequent patient transfer between units. This incident highlighted serious deficiencies in current structures and practices, and a lack of appropriate guidelines. However, there were positive outcomes from this incident. The majority of Irish dialysis patients have now been vaccinated against HBV, and lessons learned have been used to develop national guidelines on HBV vaccination and testing and on the management of incidents of blood-borne viral infections in dialysis units.
Bortezomib in relapsed or refractory mantle cell lymphoma (MCL): Results of the PINNACLE study
Authors: A. Goy, S. H. Bernstein, B. S. Kahl, B. Djulbegovic, M. J. Robertson, A. Boral, H. Shi, R. I. Fisher
Journal: Journal of Clinical Oncology (2006)

7512 Background: Bortezomib (VELCADE, Vc), a novel proteasome inhibitor, is approved in relapsed multiple myeloma and has shown activity in MCL in phase 2 NHL studies. Methods: Patients (pts) with relapsed or refractory MCL with a maximum of 2 prior therapies received Vc 1.3mg/m 2 i.v. on d 1, 4, 8, and 11 of a 21-d cycle for up to 1y. Full accrual (155 pts) was completed in this multicenter, phase 2 study. Primary endpoint was TTP, secondary endpoints included RR and duration of response (DOR). Response (International Workshop Criteria) was assessed by the investigators and separately by the sponsor using central radiology review. Results: Data are available for 154 pts. Baseline characteristics included median age 65y, 81% male, 28% KPS &lt;90%, 35% LDH &gt; normal, 43% IPI ≥3, 74% stage IV MCL. 90% of pts had prior intensive therapy (e.g. Hyper CVAD, CHOP, EPOCH), 96% had prior rituximab, and 14% had prior stem cell transplant. Median duration of Vc treatment was 4 cycles. 138 pts were evaluable for response. By investigator assessment, RR was 35% (CR + CRu = 8%) and median DOR was 9.2 mo. Median TTP was 5.5 mo (all patients, n = 154). Using central radiology review RR was 31% (CR + CRu = 7%), median DOR was 4.6 mo and median TTP was 4.1 mo. With median follow-up of 10 mo, median survival has not been reached. The most common non-hematologic AEs were fatigue (14% ≥grade 3), GI events (≥grade 3 diarrhea, abdominal pain, and nausea/vomiting in 5%, 4%, and 3%, respectively), and peripheral neuropathies (7% ≥grade 3). Hematologic toxicities were minimal except for transient thrombocytopenia (10% ≥grade 3), as previously seen with Vc. Conclusions: This study confirms the activity of Vc in relapsed/refractory MCL in a multicenter international setting and supports its rapid development as a new treatment for relapsed MCL. Vc is also being studied in the first-line setting in combination with standard chemotherapy. [Table: see text]
Bevacizumab and paclitaxel for breast cancer patients with CNS metastases
Authors: S. Labidi, T. Bachelot, I. L. Ray Coquard, B. Favier, G. Galy, J. Guastalla
Journal: Journal of Clinical Oncology (2008)

12009 Background: CNS metastases are a major problem among patients with stage IV breast cancer. Recently, many studies showed efficay of anti-VEGF drugs on brain tumors in particular glioblastoma but none explored their efficacy and tolerance on breast patients with CNS metastases. Methods: We report four cases of patients with SNC metastases treated with bevacizumab and paclitaxel. All the patients had prior whole brain radiotherapy (WBRT), PS 0–2, and radiographic evidence of progressive CNS metastases. Patients received paclitaxel 80 mg/m2 d1, d8 and d15 and bevacizumab 10 mg/kg d1, d15. Response was evaluated according to RECIST criteria. Results: Among the 4 patients, 3 had brain metastases and one had meningeal lesions. Only one patient was chemotherapy-naive. Significant anti-tumor activity was observed, with 3 partial response (PR) and one stable disease (SD) in the CNS. With a median follow-up of 7 months, duration of response was 8 months for 2 patients, 6 months for one patient and 3 months for the last patient. None presented extra-CNS progression. Conclusions: This observed antitumor activity suggests efficiency of the combination of bevacizumab and paclitaxel, and warrants further evaluation of this combination as an alternative treatment of multiple CNS metastases. No significant financial relationships to disclose.
The safety and pharmacokinetics (PK) of pemetrexed (PEM) in patients with third-space fluid (TSF)
Authors: N. J. Dickgreber, I. Díaz Padilla, L. G. Paz-Ares, L. C. Musib, Z. Yuan, J. E. Latz
Journal: Journal of Clinical Oncology (2008)

2555 Background: PEM in combination with cisplatin is an established treatment for 1st-line treatment of malignant pleural mesothelioma and, as a single agent, for 2nd-line treatment of non-small cell lung cancer. PEM structure and PK are similar to methotrexate. TSF is associated with severe toxicity following methotrexate treatment. This study evaluates PEM safety and PK in patients with TSF (pleural effusions or ascites). Methods: Approximately 30 patients with either [1] relapsed, advanced (Stage III or IV) NSCLC or [2] malignant pleural or peritoneal mesothelioma will be enrolled in this multicenter, open-label, single-agent PEM study. PEM is administered as a 10-minute intravenous infusion on day 1 of a 21-day cycle for up to 6 cycles. Folic acid and vitamin B12 are administered per label. Samples for measurement of PEM concentration in plasma are collected during cycles 1 and 2 for comparison with reference data and evaluation using population PK methods. A planned safety and PK evaluation was performed after 10 patients received 2 treatment cycles. Results: Twelve patients with varying degrees of TSF have been treated (11 with pleural effusions and 1 with ascites). Forty-nine total doses have been administered: 5 patients completed 6 treatment cycles; 4 discontinued early due to progressive disease (1 after 1 cycle, 2 after 2 cycles, 1 after 4 cycles); 3 patients are ongoing at this time (having received 2, 3, and 5 doses, respectively). Average dose intensity by patient was 95%. There were no dose reductions and 10 dose delays (7 for schedule conflicts, 3 secondary to hospitalization [1 patient, multiple hospitalizations]). There was 1 occurrence of CTCAE G3/4 toxicity that was considered to be related to study drug (G3 leucopenia). One patient was hospitalized 4 times (respiratory infection, urinary tract infection, and fever [x2], all were CTCAE G3 and not considered by the investigator to be related to study drug). No patients died during treatment. PEM plasma PK profiles were within the range of those seen previously in patients without TSF. Conclusions: PEM was well tolerated in patients with TSF. The toxicities were expected, manageable and consistent with the known PEM safety profile. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company
Use of postoperative venous thromboembolism to predict disease-specific survival in cancer patients.
Authors: R. A. Auer, A. S. Scheer, J. I. McSparron, A. R. Schulman, S. Tuorto, M. Gonen, J. Gonsalves, Y. Fong
Journal: Journal of Clinical Oncology (2010)

9032 Background: Oncology patients who develop a spontaneous venous thromboembolic event (VTE) have an inferior cancer prognosis. It is not known whether oncology patients who develop a postoperative VTE following complete surgical resection are at the same survival disadvantage as oncology patients who develop a spontaneous VTE. Methods: An institutional database at the Memorial Sloan-Kettering Cancer Center was used to identify all cancer patients who underwent abdominal, pelvic, thoracic or soft tissue procedures between January 1, 2000 and December 31, 2005. Patients who developed a VTE within 30 days of the procedure were identified from a prospective morbidity and mortality database. Stage I-III patients with a VTE following complete resection were then matched 1:10 to controls by age, sex, cancer type, stage, and surgical procedure. Overall (OS) and Disease Specific Survival (DSS) were compared for the entire cohort and for the cohort of matched patients using the Kaplan-Meier method. Results: Of the 23,541 cancer patients who underwent surgery, 474 (2%) had a postoperative VTE. The median follow-up was 24.9 months. In the entire cohort, VTE patients had a significantly worse OS at 5 years compared to controls (49.9% vs 61.1%; p <.0001). The survival difference was seen in stage I-III but not in stage IV patients. The type of VTE did not impact OS and patients with a deep vein thrombosis had a similar survival to patients with a pulmonary embolism. A total of 205 Stage I-III VTE patients who underwent a complete resection were then matched with 2050 controls by age, sex, cancer type, stage, and surgical procedure. In this matched analysis VTE patients continued to demonstrate a significantly worse prognosis with an inferior 5 year OS (54.7% vs. 66.2%; p <.0001) and DSS (67.8% vs. 80.3%; p =.0007) for VTE patients as compared to controls. Conclusions: Postoperative VTE in oncology patients with limited disease and a complete surgical resection is associated with an inferior cancer survival. A postoperative VTE remains a poor prognostic factor, even when controlling for age, stage, cancer type and surgical procedure further supporting an independent link between hypercoagulability and cancer survival. No significant financial relationships to disclose.
Randomized, open-label phase II study of motesanib or bevacizumab in combination with paclitaxel and carboplatin (P/C) for advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: G. R. Blumenschein, F. F. Kabbinavar, H. Menon, T. Mok, J. Stephenson, J. T. Beck, K. Lakshmaiah, K. Kracht, R. S. Sikorski, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2010)

7528 Background: Motesanib is a small molecule antagonist of VEGF (1, 2, and 3), PDGF, and Kit receptors. The objective of this study was to estimate the objective response rates (ORR) of motesanib (two dosing cohorts) + P/C and bevacizumab + P/C in patients (pts) with NSCLC. Methods: Adults with confirmed unresectable, stage IIIB with pericardial or pleural effusion or stage IV/recurrent nonsquamous NSCLC and ECOG 0 or 1 were randomized (1:1:1) to receive paclitaxel (200 mg/m2) + carboplatin (AUC 6 mg/mL/min) on day 1 of each 3-week cycle (6 cycles max) plus motesanib orally from day 1 of cycle 1 at either (Arm A) 125 mg once daily (QD) continuously or (Arm B) 75 mg twice daily (BID) for 5 days followed by 2 treatment-free days; or (Arm C) P/C + bevacizumab 15 mg/kg once every 3 weeks on day 1 of each cycle until disease progression or intolerability. The primary endpoint was ORR per RECIST by independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (AEs). Results: 181 pts received at least 1 dose of treatment (Arms A/B/C, n = 59/62/60). In pts with measurable disease at baseline (Arms A/B/C, n = 57/60/62) ORR in Arms A/B/C was 30/23/37%, with no complete responses. At time of data cut-off, median PFS in months (95% CI) was 8.4 (6.1, 10.1) in Arm A, 6.2 (4.7, 6.3) in Arm B, and 9.0 (7.4, 11.0) in Arm C. OS in months was 15.2 (8.5, 20.2) in Arm A, 13.9 (8.6, 18.5) in Arm B, 15.2 (10.2, 18.2) in Arm C. AEs of interest (all grades) included cholecystitis (5/8/0%), hemorrhagic events (22/24/18%), deep vein thrombosis (3/0/2%), and pulmonary embolism (3/2/3%). In Arms A/B/C, grade 3 AEs occurred in 46/58/50%, grade 4 AEs in 10/3/5%, and grade 5 AEs (excluding NSCLC progression) in 7/16/7% of pts. The most common grade ≥ 3 AEs were diarrhea (Arms A/B/C, 19/11/3%), dehydration (17/11/3%), pneumonia (7/10/2%) and neutropenia (7/8/13%). Conclusions: The estimated efficacy of motesanib 125 mg QD + P/C was similar to bevacizumab + P/C. Motesanib BID dosing had relatively lower efficacy than the other arms. The data support further study of motesanib 125 mg QD + P/C in nonsquamous NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, AstraZeneca, Eisai, Lilly, Pfizer, Roche Amgen Amgen, AstraZeneca, Lilly, Pfizer, Roche Amgen
Understanding resistance to hormonal therapy in estrogen avid breast cancer
Authors: H. M. Linden, S. Stekhova, J. M. Link, R. B. Livingston, J. R. Gralow, G. K. Ellis, L. M. Peterson, E. K. Schubert, K. A. Krohn, D. A. Mankoff
Journal: Journal of Clinical Oncology (2006)

566 Background: The estrogen receptor (ER) is an essential target for endocrine therapy in breast cancer. We, and others, have tested an in vivo assay of ER function, [F-18]-16α-fluoroestradiol (FES) PET, which allows assessment of all sites of tumor spread and predicts response to hormonal therapy. However, not all patients with tumors bearing functional ER respond to therapy, suggesting the presence of mechanisms of resistance other than ER loss. Methods: 65 postmenopausal female patients with known ER+ metastatic (mostly bone and soft tissue dominant) breast cancer treated with aromatase inhibitors underwent PET FDG and FES imaging on an institutional imaging protocol (majority in second-line therapy). Hormone levels were assayed at the time of imaging, and biopsy specimens from either the primary tumor or metastasis were analyzed for expression of ER, PR, AR, PSA, HER2neu, and TopoIIα. Results: 49 (75%) patients had at least modest levels of retained ER expression, indicated by an average FES SUV &gt; 1.5 at the tumor sites. We found serum estradiol, or estrone, levels &gt;30pg/ml in 30% of patients. We found the majority of patients had PR, or AR expression, but few had EGFR or TopoIIα expression. FES SUV &gt; 1.5 predicted response to therapy (p=.0006); no patient with an FES SUV &lt; 1.5 had an objective response. Only 18/49 patients with SUV &gt;1.5 responded to AI therapy. In the subset with FES SUV &gt; 1.5, factors predicting lack of response to AI included PR negativity (p=.038) and/or detectable serum estradiol levels (p=.05). Conclusions: Quantitative PET FES predicts response to hormonal therapy. Estrogen levels may not be completely suppressed in patients on long-term AI therapy. Estradiol levels &gt; 30pg/ml and lack of PR expression predict resistance to endocrine therapy in patients with tumors bearing functional ER expression. Efforts to monitor and reduce estradiol levels may offer therapeutic benefit to patients. No significant financial relationships to disclose.