bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.
Authors: Serafini A N , Houston S J , Resche I , Quick D P , Grund F M , Ell P J , Bertrand A , Ahmann F R , Orihuela E , Reid R H , Lerski R A , Collier B D , McKillop J H , Purnell G L , Pecking A P , Thomas F D , Harrison K A 
Published: February 2017

PURPOSE To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.
Oncologists' recognition of depression in their patients with cancer.
Authors: Passik S D , Dugan W , McDonald M V , Rosenfeld B , Theobald D E , Edgerton S 
Published: February 2017

PURPOSE This study was performed as part of a large depression screening project in cancer patients to determine the degree of physician recognition of levels of depressive symptoms in cancer patients and to describe patient characteristics that influence the accuracy of physician perception of depressive symptoms. METHODS Twenty-five ambulatory oncology clinics affiliated with Community Cancer Care, Inc of Indiana enrolled and surveyed 1,109 subjects treated by 12 oncologists. Subjects completed the Zung Self-Rating Depression Scale (ZSDS) and physicians were asked to rate their patients' level of depressive symptoms, anxiety, and pain using numerical rating scales. Subjects' sex, age, primary tumor type, medications, primary caregiver, and disease stage at diagnosis were also recorded. RESULTS Physician ratings of depression were significantly associated with their patients' levels of endorsement of depressive symptoms on the ZSDS. However, agreement between physicians and patients is most frequently clustered when patients report little or no depressive symptoms. While physician ratings are concordant with patient endorsement of no significant depressive symptomatology 79% of the time, they are only concordant 33% and 13% of the time in the mild-to-moderate/severe ranges, respectively. Physician ratings were most influenced by patient endorsement of frequent and obvious mood symptoms, ie, sadness, crying, and irritability. Physician ratings also appeared to be influenced by medical correlates of patients' level of depressive symptoms (functional status, stage of disease, and site of tumor). Additionally, patients whose depression was inaccurately classified reported significantly higher levels of pain and had higher levels of disability. Physicians' ratings of depression were most highly correlated with physicians' ratings of patients' anxiety and pain. CONCLUSION Physicians' perceptions of depressive symptoms in their patients are correlated with patient's ratings, but there is a marked tendency to underestimate the level of depressive symptoms in patients who are more depressed. They are most influenced by symptoms such as crying and depressed mood, and medical factors that are useful, but not the most reliable, indicators of depression in this population. Physicians' ratings of their patients' distress symptoms seem to be global in nature--they are highly correlated with anxiety, pain, and global dysfunction. Physician assessment might be improved if they were instructed to assess and probe for the more reliable cognitive symptoms such as anhedonia, guilt, suicidal thinking, and hopelessness. Screening instruments and the use of brief follow-up interviews would help to identify patients who are depressed.
BRCA-associated breast cancer in young women.
Authors: Robson M , Gilewski T , Haas B , Levin D , Borgen P , Rajan P , Hirschaut Y , Pressman P , Rosen P P , Lesser M L , Norton L , Offit K 
Published: February 2017

PURPOSE To delineate the clinical characteristics and outcomes of breast cancer that arises in the setting of a germline BRCA mutation and to compare BRCA-associated breast cancers (BABC) with those that arise in women without mutations. PATIENTS AND METHODS We reviewed the clinical records of 91 Ashkenazi Jewish women ascertained during studies of the genetics of early-onset breast cancer. All women underwent testing for the BRCA1 mutations 185delAG and 5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2 mutation 6174delT. RESULTS Mutations were identified in 30 women (33%). BABC were less likely to present with stage I disease than cases in women without mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%), and more likely to have extensive axillary involvement (25% v 17%). These differences were not statistically significant. BABC were significantly more likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor-negative (70% v 34%, P=.04). In the entire cohort, there were no significant differences between BABC and non-BRCA-associated cancers in 5-year relapse-free survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v 68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2 years of study entry, there was a trend toward shorter event-free survival in BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA mutations were significantly more likely to develop contralateral breast cancer at 5 years (31% v 4%, P=.0007). CONCLUSION BABC present with adverse clinical and histopathologic features when compared with cases not associated with BRCA mutations. However, the prognosis of BABC appears to be similar to that of nonassociated cancer. Further studies of incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.
What you don't know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing.
Authors: Lerman C , Hughes C , Lemon S J , Main D , Snyder C , Durham C , Narod S , Lynch H T 
Published: February 2017

PURPOSE To identify members of hereditary breast and ovarian cancer families who are at risk for adverse psychologic effects of genetic testing. PATIENTS AND METHODS A prospective cohort study with baseline (preeducation) assessments of predictor variables (ie, sociodemographic factors, cancer history, and cancer-related stress symptoms) was performed. The primary outcome variable (presence of depressive symptoms) was assessed at baseline and at 1- and 6-month follow-up evaluations. Participants were 327 adult male and female members of BRCA1- and BRCA2-linked hereditary breast and ovarian cancer families, who were identified as carriers, noncarriers, or decliners of genetic testing. RESULTS The presence of cancer-related stress symptoms at baseline was strongly predictive of the onset of depressive symptoms in family members who were invited but declined testing. Among persons who reported high baseline levels of stress, depression rates in decliners increased from 26% at baseline to 47% at 1-month follow-up; depression rates in noncarriers decreased and in carriers showed no change (odds ratio [OR] for decliners v noncarriers=8.0; 95% confidence interval [CI], 1.9 to 33.5; P=.0004). These significant differences in depression rates were still evident at the 6-month follow-up evaluation (P=.04). CONCLUSION In BRCA1/2-linked families, persons with high levels of cancer-related stress who decline genetic testing may be at risk for depression. These family members may benefit from education and counseling, even if they ultimately elect not to be tested, and should be monitored for potential adverse effects.
Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment.
Authors: Falkson G , Gelman R S , Pandya K J , Osborne C K , Tormey D , Cummings F J , Sledge G W , Abeloff M D 
Published: February 2017

PURPOSE To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR). PATIENTS AND METHODS One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy. RESULTS Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P < .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P=.74). Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment was always the most significant covariate in time-to-relapse models. CONCLUSION There is definite toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients.
Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study.
Authors: Falkson C I , Ibrahim J , Kirkwood J M , Coates A S , Atkins M B , Blum R H 
Published: February 2017

PURPOSE To investigate the response rate, time to treatment failure (TTF), overall survival, and toxicity in patients with metastatic melanoma treated with dacarbazine alone, dacarbazine plus interferon (IFN), dacarbazine plus tamoxifen (TMX), or dacarbazine plus IFN plus TMX. MATERIALS AND METHODS Two hundred seventy-one patients (258 were eligible) were randomized in a 2 x 2 factorial design to receive one of the above treatments. The trial was designed to detect a 50% improvement in survival with 83% power. RESULTS Nine complete (CRs) and 18 partial responses (PRs) were observed in the patients who received treatments that contained IFN compared with four CRs and 18 PRs in the patients who received treatments that did not contain IFN. Five CRs and 20 PRs occurred in patients treated with TMX compared with eight CRs and 16 PRs in those treated without TMX. Response differences were nonsignificant. The overall median TTF was 2.6 months, and the overall median survival was 8.9 months. There was no significant difference in TTF or survival among any of the different treatments. Poor performance status (PS), hepatic metastases, and weight loss were significant adverse prognostic factors. Twenty-three patients had a TTF greater than 20 months, and these durable responses were evenly distributed among the treatment arms. Significantly more severe and life-threatening toxic events occurred with treatments that contained IFN. CONCLUSION Neither IFN, TMX, nor the combination significantly improved the response rate, TTF, or survival when added to dacarbazine, but IFN significantly increased toxicity.
Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma.
Authors: Legha S S , Ring S , Eton O , Bedikian A , Buzaid A C , Plager C , Papadopoulos N 
Published: February 2017

PURPOSE To evaluate the antitumor activity and toxicity of concurrent biochemotherapy that uses cisplatin, vinblastine, and docarbazine (DTIC) (CVD) in combination with interferon alfa-2a (IFN-alpha) and interleukin-2 (IL-2) in patients with metastatic melanoma. PATIENTS AND METHODS Between October 1992 and October 1993, 53 patients with a documented diagnosis of metastatic melanoma with measurable lesions and an Eastern Oncology Cooperative Group (ECOG) performance status of 2 or less were enrolled onto this study. Patients were required to have no clinically significant cardiac dysfunction and to be free from symptomatic brain metastases. The treatment consisted of cisplatin 20 mg/m2 daily for 4 days; vinblastine 1.6 mg/m2 daily for 4 days; and DTIC 800 mg/m2 intravenously (i.v.) day 1 with IL-2 9 x 10(6) IU/m2 i.v. by continuous infusion daily for 4 days and IFN-alpha 5 x 10(6) U/m2 subcutaneously daily for 5 days, repeated at 21-day intervals. Response was assessed after two cycles and patients who responded were continued on treatment for a total of six cycles. RESULTS Among 53 assessable patients, 11 patients (21%) achieved a complete response (CR) and 23 patients (43%) achieved a partial response (PR), for an overall objective response rate of 64%. The median time to disease progression for all patients was 5 months. The median survival of all patients entered onto the trial was 11.8 months. Among the 11 patients who achieved a CR, five patients (9%) have remained in continuous CR for 50+ to 61+ months. The toxicity of biochemotherapy consisted of severe myelosuppression, significant nausea and vomiting, and moderately severe hypotension that required inpatient hospital care for each 5-day cycle of treatment. There were no treatment-related deaths. CONCLUSION Concurrent biochemotherapy for patients with advanced melanoma is capable of producing high CR and overall response rates and resulted in durable complete remissions in a small fraction of patients. Toxicity, although severe, was manageable in a routine inpatient hospital environment.
Polymerase chain reaction detection of melanoma cells in the circulation: relation to clinical stage, surgical treatment, and recurrence from melanoma.
Authors: Curry B J , Myers K , Hersey P 
Published: February 2017

PURPOSE The detection of melanoma cells in the circulation by polymerase chain reaction (PCR) assays has been shown by several investigators to correlate with the stage of the disease and possibly with prognosis. PATIENTS AND METHODS We performed prospective studies on 276 patients with primary melanoma and regional lymph node (LN) metastases to assess the predictive value of PCR detection of tyrosinase and melanoma antigen recognized by T cells-1 (MART-1) in the blood for recurrence of melanoma. RESULTS PCR tests for gp 100, Muc-18, and p97 reacted with RNA in blood from healthy subjects and were considered unsuitable for patient monitoring. The tests were most frequently positive in the first 3 months after surgery. There were 47 recurrences in 123 patients who had been followed up for 18 months. Assays within 3 months of surgery predicted recurrence from melanoma in 66% of the latter (tests for tyrosinase alone detected 51% and MART-1 alone 21% of the patients). Hence, 34% of recurrences were not predicted by tests in the early postoperative period. This did not appear to be because of marker-negative melanoma because summation of tests over the first year identified 89% of those with recurrent disease. CONCLUSION Positive tests were recorded in 35% of patients who remained disease free, but it is too early to assess whether these represent false-positive results. The false-negative results raise the question of whether the assays will provide a reliable basis for selection of patients for adjuvant therapy.
Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial.
Authors: Riethmüller G , Holz E , Schlimok G , Schmiegel W , Raab R , Höffken K , Gruber R , Funke I , Pichlmaier H , Hirche H , Buggisch P , Witte J , Pichlmayr R 
Published: February 2017

PURPOSE As previously shown, antibody treatment increased survival of patients with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we performed a 7-year analysis with only four of 189 patients monitored for less than 5 years. PATIENTS AND METHODS A total of 189 patients with resected Dukes' C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17-1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n=99), or to observation only (n=90). Primary end points were overall survival and disease-free interval. Patients were stratified by a dynamic randomization according to center, sex, location of tumor, number of affected lymph nodes, and preoperative carcinoembryonic antigen concentration. RESULTS Randomization produced balanced distribution of risk factors. After 7 years of follow-up evaluation, treatment had reduced overall mortality by 32% (Cox's proportional hazard, P < .01; log-rank, P=.01) and decreased the recurrence rate by 23% (Cox's proportional hazard, P < .04; log-rank, P=.07). The intention-to-treat analysis gave a significant effect for overall survival (Cox's proportional hazard, P < .01; log-rank, P=.02) and disease-free survival (Cox's proportional hazard, P=.02; log-rank, P=.11 ). While distant metastases were significantly reduced (Cox's proportional hazard, P=.004; log-rank, P=.004), local relapses were not (Cox's proportional hazard, P=.65; log-rank, P=.52). This differential effect of 17-1A antibody on disseminated isolated tumor cells versus occult local satellites may explain the increased significance seen in the overall survival. CONCLUSION The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.
Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine.
Authors: Budman D R , Meropol N J , Reigner B , Creaven P J , Lichtman S M , Berghorn E , Behr J , Gordon R J , Osterwalder B , Griffin T 
Published: February 2017

PURPOSE To evaluate the toxicology and pharmacology of an orally active fluoropyrimidine given as a continuous daily dose divided into two portions for 6 weeks, and to determine the maximal-tolerated daily dose (MTD) and the suggested phase II daily dose. PATIENTS AND METHODS Solid-tumor patients with a Karnofsky performance status greater than 70 who had normal organ function and resolution of the effects of prior therapy, and who gave informed written consent, were enrolled. Oral capecitabine, as a divided morning and evening dose, was administered to cohorts of a minimum of 3 patients starting at 110 mg/m2 and escalating by means of a modified Fibonacci scheme to 1,657 mg/m2/d. Pharmacologic samples were obtained on days 1 and 15. Toxicity evaluations were performed approximately every 3 days for the first 43 days. Antitumor effect was evaluated at day 42 of therapy. RESULTS Thirty-three patients entered the study. Few side effects occurred at or below 1,331 mg/m2/d. The MTD was 1,657 mg/m2/d with limiting toxicities of palmar-plantar erythrodysesthesia, nausea, vomiting, vertigo, abdominal pain, diarrhea, and thrombocytopenia. All toxicities were reversible. A mixed response was seen in one breast cancer patient. Pharmacologic studies showed rapid and extensive metabolism of the parent drug into cytotoxic metabolites with a maximum plasma concentration (Cmax) 1 hour after ingestion. Linear increases in the area under the concentration-time curve (AUC) and Cmax were seen with linear increases in administered dose. CONCLUSION The suggested phase II dose on a continuous 42-day dosing schedule is 1,331 mg/m2/d. Linear pharmacologic parameters of the parent compound and metabolites are demonstrated.
Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer.
Authors: Smith D C , Dunn R L , Strawderman M S , Pienta K J 
Published: February 2017

PURPOSE Prostate-specific antigen (PSA) has been used as a marker of advanced prostate cancer but remains controversial. To evaluate PSA as a predictor of survival, we analyzed data from sequential phase II trials of estramustine and etoposide. METHODS A landmark analysis that used data from 62 men with PSA levels at baseline and 8 weeks was conducted. The best PSA measure (of six evaluated) was incorporated into a multiple regression model with performance status (PS); relative change in PSA level; and pretreatment PSA, alkaline phosphatase, and hemoglobin values. RESULTS A decrease in PSA of 50% or greater at 8 weeks was associated with a significantly increased survival (P=.0005, two-sided log-rank test). Median survival from the landmark was 91 weeks in patients with a 50% or greater decrease at 8 weeks versus 38 weeks in those without this decrease. Modeling showed that PS, pretreatment hemoglobin level, and relative change in PSA level were significant prognostic factors, with a significant interaction between PS and pretreatment hemoglobin level. In the final model, a relative change in PSA level at 8 weeks of less than 50% had an adjusted relative risk of 2.20 (95% confidence interval, 1.21 to 4.00). A decrease in PSA level of 50% or greater at any time during therapy was associated with a response in measurable disease (P=.0369, two-sided Fisher's exact test). CONCLUSION The PSA value after 8 weeks of this cytotoxic regimen does predict survival. A decrease in PSA level is associated with both survival and response in soft tissue lesions and should be incorporated into the response criteria and reporting of trials of cytotoxic agents in prostate cancer.