bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influences on Oncologists’ Adoption of New Agents in Adjuvant Chemotherapy of Breast Cancer
Authors: Buban Gina M. , Link Brian K. , Doucette William R. 
Published: February 2017

PURPOSE: Little is known about how oncologists’ adopt new treatments for breast cancer. This study investigated influences on oncologists’ adoption of paclitaxel as adjuvant chemotherapy for early-stage breast cancer, 9 months after presentation of phase III data suggesting improved disease-free and overall survival when paclitaxel was added to doxorubicin and cyclophosphamide for such patients. METHODS: Self-reported data were collected with a mail survey of a random sample of 1,200 oncologists practicing in the United States. Using Rogers’ model, we measured four types of influences on adoption of innovation: (1) communication channels, (2) innovation characteristics, (3) a practitioner’s social system, and (4) physician characteristics. Multiple regression analysis assessed the associations between oncologist adoption of paclitaxel for early-stage breast cancer patients and variables representing the modeled influences on adoption. RESULTS: On average, respondents (n = 181) reported having adopted paclitaxel for 37% of their early-stage breast cancer patients. The overall model was significant, with seven variables associated (P ≤ .05) with adoption of paclitaxel. Significant influences on adoption included use of symposia as a therapy information source, physician experience with paclitaxel to treat late-stage breast cancer, and perceived advantage in efficacy of paclitaxel. CONCLUSION: As new modalities become available to treat cancer, it is vital to understand what factors influence oncologists and patients when choosing to use them. Those parties interested in fostering the adoption of new breast cancer treatments should address features of communication channels (eg, use of symposia), characteristics of new treatments (eg, perceived advantage in efficacy), physicians’ social systems (eg, patient requests), and characteristics of potential adopters (eg, previous experience with the treatment).
Estimation of Risk of Inherited Medullary Thyroid Carcinoma in Apparent Sporadic Patients
Authors: Wiench M. , Wygoda Z. , Gubala E. , Wloch J. , Lisowska K. , Krassowski J. , Scieglinska D. , Fiszer-Kierzkowska A. , Lange D. , Kula D. , Zeman M. , Roskosz J. , Kukulska A. , Krawczyk Z. , Jarzab B. 
Published: February 2017

PURPOSE: The study was undertaken to evaluate the frequency of inherited medullary thyroid carcinoma (MTC) among patients with apparent sporadic disease. A stepwise algorithm was used depending on clinical indices and the age of patient at MTC diagnosis. PATIENTS AND METHODS: One hundred sixteen patients with MTC verified by postoperative pathologic examination were subjected to genetic analysis of RET exons 10, 11, 13, 14, and 16 by means of polymerase chain reaction, restriction endonuclease digestion, and DNA sequencing. RESULTS: Among 116 apparent sporadic MTC patients, we identified eleven (9.5%) RET germline mutation carriers. Seven of these (6.0%) were found by routine analysis (exons 10 and 11). The frequency of inherited disease among patients younger than 45 years at diagnosis was 10.2% by analysis of typical mutations in exons 10 and 11. Extended genetic analysis (sequencing of exons 11, 13, 14, and 16) yielded 6.1% additional diagnoses, giving a risk of 16.3% in this age group. One previously unreported mutation in exon 11 affected codon 649 (TCG>TTG, Ser>Leu). In the true sporadic MTC patients younger than 30 years at diagnosis, frequencies of 36% and 4.5% in polymorphic variants L769L and S836S, respectively, were observed. The frequency for L769L was higher than in older patients (P < .05). CONCLUSION: The frequency of inherited disease among apparent sporadic medullary thyroid carcinoma patients is close to 10% in the Polish population of MTC patients. The extended analysis of all known RET proto-oncogene mutation sites is obligatory in patients younger than 45 years at diagnosis, but we also see the need to analyze the impact of rarer mutations in older patients.
Health-Related Quality-of-Life Effects of Radical Prostatectomy and Primary Radiotherapy for Screen-Detected or Clinically Diagnosed Localized Prostate Cancer
Authors: Madalinska Joanna B. , Essink-Bot Marie-Louise , de Koning Harry J. , Kirkels Wim J. , van der Maas Paul J. , Schröder Fritz H. 
Published: February 2017

PURPOSE: The current study was undertaken within the framework of a screening trial to compare the health-related quality-of-life (HRQOL) outcomes of two primary treatment modalities for localized prostate cancer: radical prostatectomy and external-beam radiotherapy. PATIENTS AND METHODS: We conducted a prospective longitudinal cohort study among 278 patients with early screen-detected (59%) or clinically diagnosed (41%) prostate cancer using both generic and disease-specific HRQOL measures (SF-36, UCLA Prostate Cancer Index [urinary and bowel modules] and items relating to sexual functioning) at three points in time: t1 (baseline), t2 (6 months later), and t3 (12 months after t1). RESULTS: Questionnaires were completed by 88% to 93% of all initially enrolled patients. Patients referred for primary radiotherapy were significantly older than prostatectomy patients (63 v 68 years, P < .01). Analyses (adjusted for age and pretreatment level of functioning) revealed poorer levels of generic HRQOL after radiotherapy. Prostatectomy patients reported significantly higher (P < .01) posttreatment incidences of urinary incontinence (39% to 49%) and erectile dysfunction (80% to 91%) than radiotherapy patients (respectively, 6% to 7% and 41% to 55%). Bowel problems (urgency) affected 30% to 35% of the radiotherapy group versus 6% to 7% of the prostatectomy group (P < .01). Patients with screen-detected and clinically diagnosed cancer reported similar posttreatment HRQOL. CONCLUSION: Prostatectomy and radiotherapy differed in the type of HRQOL impairment. Because the HRQOL effects may be valued differently at the individual level, patients should be made fully aware of the potential benefits and adverse consequences of therapies for early prostate cancer. Differences in posttreatment HRQOL were not related to the method of cancer detection.
Twenty-Two Years of Phase III Trials for Patients With Advanced Non–Small-Cell Lung Cancer: Sobering Results
Authors: Breathnach Oscar S. , Freidlin Boris , Conley Barbara , Green Mark R. , Johnson David H. , Gandara David R. , O’Connell Michael , Shepherd Frances A. , Johnson Bruce E. 
Published: February 2017

PURPOSE: To determine the changes in clinical trials and outcomes of patients with advanced-stage non–small-cell lung cancer (NSCLC) treated on phase III randomized trials initiated in North America from 1973 to 1994. PATIENTS AND METHODS: Phase III trials for patients with advanced-stage NSCLC were identified through a search of the National Cancer Institute’s Cancer Therapy Evaluation Program database from 1973 to 1994, contact with Cooperative Groups, and by literature search of MEDLINE. Patients with advanced NSCLC treated during a similar time interval were also examined in the SEER database. Trends were tested in the number of trials, in the number and sex of patients entered on the trials, and in survival over time. RESULTS: Thirty-three phase III trials were initiated between 1973 and 1994. Twenty-four trials (73%) were initiated within the first half of this period (1973 to 1983) and accounted for 5,359 (64%) of the 8,434 eligible patients. The median number of patients treated per arm of the trials rose from 77 (1973 to 1983) to 121 (1984 to 1994) (P < .001). Five trials (15%) showed a statistically significant difference in survival between treatment arms, with a median prolongation of the median survival of 2 months (range, 0.7 to 2.7 months). CONCLUSION: Analysis of past trials in North America shows that the prolongation in median survival between two arms of a randomized study was rarely in excess of 2 months. Techniques for improved use of patient resources and appropriate trial design for phase III randomized therapeutic trials with patients with advanced NSCLC need to be developed.
Localized Ewing Tumor of Bone: Final Results of the Cooperative Ewing’s Sarcoma Study CESS 86
Authors: Paulussen M. , Ahrens S. , Dunst J. , Winkelmann W. , Exner G.U. , Kotz R. , Amann G. , Dockhorn-Dworniczak B. , Harms D. , Müller-Weihrich S. , Welte K. , Kornhuber B. , Janka-Schaub G. , Göbel U. , Treuner J. , Voûte P.A. , Zoubek A. , Gadner H. , Jürgens H. 
Published: February 2017

PURPOSE: Cooperative Ewing’s Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for “high risk” (HR, n = 241), and small extremity lesions for “standard risk” (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and ≥100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P = .92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P = .0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P = .0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.
Phase I Study of a Third-Generation Selective Estrogen Receptor Modulator, LY353381.HCl, in Metastatic Breast Cancer
Authors: Münster Pamela N. , Buzdar Aman , Dhingra Kapil , Enas Nathan , Ni Lan , Major Maureen , Melemed Allen , Seidman Andrew , Booser Daniel , Theriault Richard , Norton Larry , Hudis Clifford 
Published: February 2017

PURPOSE: We conducted this phase I trial to determine the safety and toxicity profile of LY353381.HCl—a novel, potent, third-generation selective estrogen receptor modulator (SERM)—because this benzothiophene derivative demonstrated an SERM profile in preclinical studies. PATIENTS AND METHODS: We studied 32 patients with recurrent or metastatic breast cancer. Patients were treated in four cohorts with oral daily doses of 10, 20, 50, and 100 mg. Pharmacokinetic sampling was performed during the first 72 hours following the first dose on day 1 and during the 24 hours after the day 57 dose. Eligibility criteria included Eastern Cooperative Oncology Group performance status of 0 to 2; no significant major organ dysfunction; and at least 3 weeks elapsed since most recent hormonal therapy, chemotherapy, and estrogen replacement therapy. RESULTS: The median patient age was 56 years (range, 30 years to 76 years). The median number of prior chemotherapies for metastatic disease was one (range, zero to four), while the median number of prior hormone regimens for metastatic disease was two (range, zero to five). Receptor status was estrogen receptor (ER) positive and progesterone receptor (PR) positive, 19 patients; ER positive and PR negative, eight patients; ER positive and PR unknown, two patients; and ER and PR unknown, three patients. Dose-limiting toxicity was not observed. Treatment was well tolerated with mild to moderate hot flashes in 18 of 32 patients (56%) at all dose levels. Transvaginal ultrasound performed at baseline and after 12 weeks of treatment showed no endometrial thickening. Of the 32 patients evaluable for response, six patients had stable disease for at least 6 months with a median duration of 7.7 months (range, 6.2 months to 33.8 months). The pharmacokinetics of LY353381.HCl were generally linear with respect to time and studied dose range. CONCLUSION: As predicted in preclinical testing, daily oral LY353381.HCl is safe, is well tolerated at all tested dose levels, and may be clinically beneficial in patients with extensively pretreated metastatic breast cancer. Further studies with LY353381 to evaluate the efficacy in patients with or without prior exposure to tamoxifen and fewer overall prior regimens are under way.
Low-Volume Nodal Metastases Detected at Retroperitoneal Lymphadenectomy for Testicular Cancer: Pattern and Prognostic Factors for Relapse
Authors: Rabbani Farhang , Sheinfeld Joel , Farivar-Mohseni Hesam , Leon Antonio , Rentzepis Michael J. , Reuter Victor E. , Herr Harry W. , McCaffrey John A. , Motzer Robert J. , Bajorin Dean F. , Bosl George J. 
Published: February 2017

PURPOSE: To determine the incidence, pattern, and predictive factors for relapse in patients with low-volume nodal metastases (stage pN1) at retroperitoneal lymphadenectomy (RPLND) and identify who may benefit from chemotherapy in the adjuvant or primary setting. PATIENTS AND METHODS: Fifty-four patients with testicular nonseminomatous germ cell tumor had low-volume retroperitoneal metastases (pathologic stage pN1, 1997 tumor-node-metastasis classification) resected at RPLND, 50 of whom were managed expectantly without adjuvant chemotherapy. The dissection was bilateral in 12 and was a modified template in 38 patients. Retroperitoneal metastases were limited to microscopic nodal involvement in 14 patients. Follow-up ranged from 1 to 106 months (median, 31.4 months). RESULTS: Eleven patients (22%) suffered a relapse at a median follow-up of 1.8 months (range, 0.6 to 28 months). The most frequent form of recurrence was marker elevation in nine (18%) patients. Persistent marker elevation after orchiectomy and before retroperitoneal lymphadenectomy was a significant independent predictor of relapse (relative risk, 8.0; 95% confidence interval, 2.3 to 27.8; P = .001). Four of five (80%) patients with elevated markers (alpha-fetoprotein alone in three, alpha-fetoprotein and beta human chorionic gonadotropin in one) suffered a relapse, compared with seven of 45 (15.6%) patients with normal markers. CONCLUSION: Clinical stage I and IIA patients with normal markers who have low-volume nodal metastases have a low incidence of relapse and can be managed by observation only if compliance can be assured. In contrast, patients with elevated markers before retroperitoneal lymphadenectomy have a high rate of relapse and should be considered for primary chemotherapy.
Comparison of Oral Capecitabine Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Treatment in 605 Patients With Metastatic Colorectal Cancer: Results of a Randomized Phase III Study
Authors: Hoff Paulo M. , Ansari Rafat , Batist Gerald , Cox John , Kocha Walter , Kuperminc Mario , Maroun Jean , Walde David , Weaver Charles , Harrison Evelyn , Burger Hans U. , Osterwalder Bruno , Wong Alfred O. , Wong Ralf 
Published: February 2017

PURPOSE: To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer. PATIENTS AND METHODS: We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles. RESULTS: The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P = .005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P = .72), median times to treatment failure were 4.1 and 3.1 months (P = .19), and median overall survival times were 12.5 and 13.3 months (P = .974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P < .0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P < .0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P < .00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment. CONCLUSION: Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.
Phase I and Pharmacokinetic Study of BMS-184476, a Taxane With Greater Potency and Solubility Than Paclitaxel
Authors: Hidalgo Manuel , Aylesworth Cheryl , Hammond Lisa A. , Britten Carolyn D. , Weiss Geoffrey , Stephenson Joseph , Schwartz Garry , Patnaik Amita , Smith Lon , Molpus Kathleen , Felton Sally , Gupta Elora , Ferrante Karen J. , Tortora Anne , Sonnichsen Daryl S. , Skillings Jamey , Rowinsky Eric K. 
Published: February 2017

PURPOSE: To assess the feasibility, toxicity, pharmacokinetics, and preliminary activity of BMS-184476 administered as a 1-hour intravenous (IV) infusion every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of BMS-184476 as a 1-hour IV infusion every 3 weeks without premedication to prevent hypersensitivity reactions (HSR). Plasma sampling and urine collections were performed to characterize the pharmacokinetics and pharmacodynamics of BMS-184474. RESULTS: Thirty-four patients were treated with 78 courses of BMS-184476 at five dose levels ranging from 20 to 80 mg/m2. Dose-limiting toxicity (DLT), consisting of severe neutropenia with fever, severe diarrhea, and/or severe mucositis, was experienced during course 1 by six of nine minimally pretreated patients treated at the 70 and 80 mg/m2 dose level. In contrast, of 15 assessable patients treated at the 60 mg/m2 dose level, which is the maximum-tolerated dose (MTD) of BMS-184476 on this administration schedule, only one heavily pretreated patient developed DLT (grade 4 neutropenia with fever and grade 3 diarrhea). One patient developed a grade 2 HSR during a second course of BMS-184476 at the 40 mg/m2 dose level. A previously untreated patient with an advanced cholangiocarcinoma experienced a partial response, and a patient with an untreated carcinoma of the gastroesophageal junction had a minor response. The pharmacokinetics of BMS-184476 seemed linear in the dose range studied. Mean ± SD values for clearance, volume of distribution at steady-state, and terminal half-life were 220 ± 89 mL/min/m2, 402 ± 231 L/m2, and 40.8 ± 21.8 hours, respectively. CONCLUSION: The MTD and recommended dose for phase II evaluations of BMS-184476 is 60 mg/m2 as a 1-hour IV infusion every 3 weeks. The results of this study suggest that BMS-184476 may have several advantages compared with paclitaxel in terms of toxicity, pharmacokinetics, pharmaceutics, and administration and warrants further clinical development.
Health Outcomes After External-Beam Radiation Therapy for Clinically Localized Prostate Cancer: Results From the Prostate Cancer Outcomes Study
Authors: Hamilton A. S. , Stanford J. L. , Gilliland F. D. , Albertsen P. C. , Stephenson R. A. , Hoffman R. M. , Eley J. W. , Harlan L. C. , Potosky A. L. 
Published: February 2017

PURPOSE: Studies reporting effects of radiotherapy for prostate cancer on sexual, bowel, and urinary function have been conducted primarily in referral centers or academic institutions. Effects of external-beam radiotherapy for prostate cancer among a population-based cohort were assessed. PATIENTS AND METHODS: The study population included 497 white, Hispanic, and African-American men with localized prostate cancer from six US cancer registries who were diagnosed between October 1, 1994, and October 31, 1995, and treated initially with external-beam radiotherapy. They were interviewed at regular intervals, and medical records were reviewed. Distributions of responses for bowel-, urinary-, and sexual-related functions at 6, 12, and 24 months after diagnosis and adjusted mean composite change scores for each domain were analyzed. RESULTS: Declines of 28.9% in the sexual function score and 5.4% in the bowel function score occurred by 24 months, whereas at this time, the urinary function score was relatively unchanged. A total of 43% of those who were potent before diagnosis became impotent after 24 months. More than two thirds of the men were satisfied with their treatment and would make the same decision again. CONCLUSION: Sexual function was the most adversely affected quality-of-life domain, with problems continuing to increase between 12 and 24 months. Bowel function problems increased at 6 months, with partial resolution observed by 24 months. Despite the side effects, satisfaction with therapy was high. These results are representative of men in community practice settings and may be of assistance to men and to clinicians when making treatment decisions.
Pharmacodynamic Studies of the Epidermal Growth Factor Receptor Inhibitor ZD1839 in Skin From Cancer Patients: Histopathologic and Molecular Consequences of Receptor Inhibition
Authors: Albanell Joan , Rojo Federico , Averbuch Steve , Feyereislova Andrea , Mascaro Jose Manuel , Herbst Roy , LoRusso Patricia , Rischin Danny , Sauleda Silvia , Gee Julia , Nicholson Robert I. , Baselga Jose 
Published: February 2017

PURPOSE: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals, Alderley Park, United Kingdom) is under development as an anticancer agent. We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin, an EGFR-dependent tissue, in cancer patients participating in ZD1839 phase I clinical trials. PATIENTS AND METHODS: We studied 104 pre– and/or on–ZD1839 therapy (≈ at day 28 of therapy) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839. We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated (phosphorylated) EGFR. Effects on receptor signaling (activated mitogen-activated protein kinase [MAPK]), proliferation, p27KIP1, and maturation were also assessed. RESULTS: Histopathologically, the stratum corneum of the epidermis was thinner during therapy (P < .001). In hair follicles, prominent keratin plugs and microorganisms were found in dilated infundibula. ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells (P < .001). In addition, ZD1839 inhibited MAPK activation (P < .001) and reduced keratinocyte proliferation index (P < .001). Concomitantly, ZD1839 increased the expression of p27KIP1 (P < .001) and maturation markers (P < .001) and increased apoptosis (P < .001). These effects were observed at all dose levels, before reaching dose-limiting toxicities. CONCLUSION: ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo. These effects were profound at doses well below the one producing unacceptable toxicity, a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials.