bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Trial of Tamoxifen Versus Tamoxifen Plus Aminoglutethimide as Adjuvant Treatment in Postmenopausal Breast Cancer Patients With Hormone Receptor-Positive Disease: Austrian Breast and Colorectal Cancer Study Group Trial 6
Authors: Schmid Marianne , Jakesz Raimund , Samonigg Hellmut , Kubista Ernst , Gnant Michael , Menzel Christian , Seifert Michael , Haider Karin , Taucher Susanne , Mlineritsch Brigitte , Steindorfer Peter , Kwasny Werner , Stierer Michael , Tausch Christoph , Fridrik Michael , Wette Viktor , Steger Günther , Hausmaninger Hubert
Published: March 2003

Purpose: To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor–positive, early-stage breast cancer.

Patients and Methods: A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years.

Results: All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P = .89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P = .74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P = .0001).

Conclusion: Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.
Quantitation of GD2 Synthase mRNA by Real-Time Reverse Transcriptase Polymerase Chain Reaction: Clinical Utility in Evaluating Adjuvant Therapy in Neuroblastoma
Authors: Cheung Irene Y. , Lo Piccolo M. Serena , Kushner Brian H. , Kramer Kim , Cheung Nai-Kong V.
Published: March 2003

Purpose: Minimal residual disease (MRD) is one of the final hurdles to cancer cure. Because therapy (myeloablation, immunotherapy, or differentiation) for MRD is applied at the time of clinical remission, objective surrogate markers are needed to gauge treatment efficacy.

Patients and Methods: Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) of GD2 synthase (β1,4-N-acetylgalactosaminyltransferase, EC 2.4.1.92 ) mRNA, we evaluated MRD response to anti-GD2 monoclonal antibody 3F8 adjuvant therapy, namely, one cycle of radioimmunotherapy using iodine-131 (131I)-3F8 plus one cycle of unlabeled 3F8 in 45 stage 4 neuroblastoma patients (newly diagnosed or without prior relapse) on the N7 protocol at Memorial Sloan-Kettering Cancer Center. The prognostic effect of MRD in their bone marrows before and after this phase of adjuvant therapy on progression-free survival (PFS) and overall survival (OS) was also analyzed.

Results: Before 3F8 treatment, 24 of 45 patients were in complete remission (CR), 12 were in very good partial remission (VGPR), and nine were in partial remission (PR), according to criteria from International Neuroblastoma Staging System plus 131I-3F8 scan; 71% had detectable tumor cells in marrow by real-time RT-PCR. Of the 32 positive patients, 20 became negative after therapy, with a 63% efficacy. When patients were stratified by CR/VGPR versus PR, GD2 synthase positivity was prognostic when detected before 3F8-targeted therapy (PFS, P = .045 and OS, P = .010). Persistent marker positivity was also predictive of PFS (P = .035) and OS (P = .027). Patients who succumbed to the disease had transcript levels four times higher than those who remain alive.

Conclusion: GD2 synthase mRNA is a useful surrogate marker for evaluating adjuvant treatment efficacy in neuroblastoma with prognostic potential.
Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer
Authors: Henderson I. Craig , Berry Donald A. , Demetri George D. , Cirrincione Constance T. , Goldstein Lori J. , Martino Silvana , Ingle James N. , Cooper M. Robert , Hayes Daniel F. , Tkaczuk Katherine H. , Fleming Gini , Holland James F. , Duggan David B. , Carpenter John T. , Frei Emil , Schilsky Richard L. , Wood William C. , Muss Hyman B. , Norton Larry
Published: March 2003

Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival.

Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor–positive tumors.

Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor–negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor–positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest.

Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
Quality of Life in Good Prognosis Patients With Metastatic Germ Cell Cancer: A Prospective Study of the European Organization for Research and Treatment of Cancer Genitourinary Group/Medical Research Council Testicular Cancer Study Group (30941/TE20)
Authors: Fosså Sophie D. , de Wit Ronald , Roberts J. Trevor , Wilkinson Peter M. , de Mulder Pieter H.M. , Mead Graham M. , Cook Pat , de Prijck Linda , Stenning Sally , Aaronson Neil K. , Bottomley Andrew , Collette Laurence
Published: March 2003

Purpose: To describe global quality of life (GLQL) in patients with metastatic testicular cancer (TC) treated with four different schedules of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (four v three cycles given over 5 v 3 days).

Patients and Methods: Quality-of-life data were prospectively collected in 666 patients with metastatic TC entered into the European Organization for Research and Treatment of Cancer (EORTC) Trial 30941/United Kingdom Medical Research Council Trial TE20, using the EORTC Quality-of-Life Questionnaire C30 and a TC module. Data were analyzed by a mixed effects model and by evaluation of clinically relevant changes at 2 years.

Results: The pattern of GLQL changes was similar in the four groups. Two years after chemotherapy, 36% of patients displayed improved GLQL as compared with baseline, whereas GLQL had deteriorated in 13%. At 3 months, patients receiving the 3-day regimen experienced increased gastrointestinal (GI) toxicity more than those receiving the 5-day regimen, with the difference reaching the level of clinical relevance (≥ 10-point change) if four cycles were given. The 3-day schedule increased the 2-year risk of tinnitus, with clinical relevance demonstrated after four cycles. Long-term peripheral neuropathy and Raynaud-like phenomena were not associated with the number of cycles or days per cycle. At 2 years, Raynaud-like phenomena, tinnitus, or reduced hearing were reported by 21% to 26% of the patients.

Conclusion: Because of the excess of acute GI toxicity and the increased risk of tinnitus after the 3-day regimen, we recommend the 5-day regimen if four cycles of BEP are planned. If only three cycles are to be given, then the 3-day regimen is acceptable, even given the increased risk of nausea/vomiting at 3 months.
Maternal Preoccupation and Parenting as Predictors of Emotional and Behavioral Problems in Children of Women With Breast Cancer
Authors: Sigal John J. , Perry J. Christopher , Robbins James M. , Gagné Marie-Anik , Nassif Edgard
Published: March 2003

Purpose: To test the hypothesis that differences between sicker and not-so-sick women in their preoccupation with their illness and parenting behavior can explain why some investigators find that children of breast cancer patients fare better than controls and other investigators find the reverse.

Patients and Methods: Forty-two women with metastasized breast cancer (sicker mothers) and 45 women with a first occurrence of nonmetastasized breast cancer (not-so-sick mothers) rated the degree of their preoccupation with the disease, their parenting behavior, mood, and social supports and the emotional and behavioral symptoms in one of their children. Their 12- to 18-year-old children rated their mothers’ parenting behavior, their own emotional and behavioral symptoms, and their self-esteem.

Results: Sicker mothers reported relatively less preoccupation. They, and their children, reported less poor parenting and fewer externalizing symptoms in the children. Regression analyses revealed further differences between the groups.

Conclusion: Less preoccupation with their illness and less poor parenting behavior by sicker mothers may explain why their children seem to fare better then those of not-so-sick mothers. Formulations concerning families of breast cancer patients should include consideration of the effect of the mothers’ perception of the severity of their illness.
Treatment of Primary CNS Lymphoma With Methotrexate and Deferred Radiotherapy: A Report of NABTT 96–07
Authors: Batchelor Tracy , Carson Kathryn , O’Neill Alison , Grossman Stuart A. , Alavi Jane , New Pamela , Hochberg Fred , Priet Regina
Published: March 2003

Purpose: A multicenter, phase II study of single-agent, intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium.

Methods: Methotrexate (8 g/m2) was initially administered every 2 weeks. The primary end point was radiographic CR or PR, as defined by standard radiographic criteria, and secondary end points were survival and drug-related toxicity.

Results: Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80. Three of 14 patients who underwent lumbar puncture had malignant cells on CSF cytopathology, and five of 25 patients had ocular involvement. Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another. All patients have completed the treatment program or progressed. Among 23 patients, there were 12 CR (52%), five PR (22%), one (4%) with stable disease, and five progressions (22%) while on therapy. Seven patients died of tumor progression, and two died of other causes. Median progression-free survival was 12.8 months. Median overall survival for the entire group had not been reached at 22.8+ months. The toxicity of this regimen was modest, with no grade 3 or 4 toxicity in 13 of 25 patients, grade 3 toxicity in eight of 25 patients, and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy.

Conclusion: These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion (74%) comparable to more toxic regimens.
Identifying Potential Indicators of the Quality of End-of-Life Cancer Care From Administrative Data
Authors: Earle Craig C. , Park Elyse R. , Lai Bonnie , Weeks Jane C. , Ayanian John Z. , Block Susan
Published: March 2003

Purpose: To explore potential indicators of the quality of end-of-life services for cancer patients that could be monitored using existing administrative data.

Methods: Quality indicators were identified and assessed by literature review for proposed indicators, focus groups with cancer patients and family members to assess candidate indicators and generate new ideas, and an expert panel ranking the meaningfulness and importance of each potential indicator using a modified Delphi approach.

Results: There were three major concepts of poor quality of end-of-life cancer care that could be examined using currently-available administrative data (such as Medicare claims): institution of new anticancer therapies or continuation of ongoing treatments very near death; a high number of emergency room visits, inpatient hospital admissions, or intensive care unit days near the end of life; and a high proportion of patients never enrolled in hospice, only admitted in the last few days of life, or dying in an acute-care setting. Concepts such as access to psychosocial and other multidisciplinary services and pain and symptom control are important and may eventually be feasible, but they cannot currently be applied in most data systems. Indicators based on limiting the use of treatments with low probability of benefit or indicators based on economic efficiency were not acceptable to patients, family members, or physicians.

Conclusion: Several promising claims-based quality indicators were identified that, if found to be valid and reliable within data systems, could be useful in identifying health-care systems in need of improving end-of-life services.
Economic Evaluation of Breast Cancer Treatment: Considering the Value of Patient Choice
Authors: Polsky Daniel , Mandelblatt Jeanne S. , Weeks Jane C. , Venditti Laura , Hwang Yi-Ting , Glick Henry A. , Hadley Jack , Schulman Kevin A.
Published: March 2003

Purpose: To use 5 years of primary data to compare the incremental cost-effectiveness of breast conservation and radiation versus mastectomy with the restriction of choice to a single therapy versus providing a choice of either therapy.

Patients and Methods: We evaluated a random retrospective cohort of 2,517 Medicare beneficiaries treated for newly diagnosed stage I or II breast cancer from 1992 through 1994. The outcome measures were quality-adjusted life-years (QALYs) and 5-year medical costs. Risk and propensity score adjustments were used in the analysis.

Results: A breast conservation and radiation regimen has significantly higher costs than mastectomy in the first year after surgery; the adjusted 5-year costs are $14,054 (95% confidence interval, $9,791 to $18,312) greater than those of mastectomy. The adjusted incremental cost-effectiveness ratio comparing breast conservation and radiation to mastectomy was $219,594 per QALY for the comparison of the two strategies. If the possibility of patient choice from maintaining the availability of multiple treatments versus restricting choice to mastectomy alone provides a quality-of-life gain of 0.031 QALYs, then the cost-effectiveness ratio of this choice option is $80,440 per QALY.

Conclusion: The current system of providing a choice between mastectomy and breast conservation surgery is economically attractive when the economic analysis includes the benefit of patient choice of treatment.
Randomized Phase I/II Study of Troxacitabine Combined With Cytarabine, Idarubicin, or Topotecan in Patients With Refractory Myeloid Leukemias
Authors: Giles Francis J. , Faderl Stefan , Thomas Deborah A. , Cortes Jorge E. , Garcia-Manero Guillermo , Douer Dan , Levine Alexandra M. , Koller Charles A. , Jeha Sima S. , O’Brien Susan M. , Estey Elihu H. , Kantarjian Hagop M.
Published: March 2003

Purpose: Troxacitabine has significant single-agent activity. This study was conducted to define the dose-limiting toxicities (DLTs) of its combination with cytarabine (ara-C), idarubicin, or topotecan.

Patients and Methods: Patients with refractory acute myeloid leukemia (AML), advanced myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP) were initially randomly assigned to receive troxacitabine 5.0 mg/m2 by intravenous (IV) infusion over 30 minutes on days 1 to 5 with ara-C 1.0 mg/m2/d IV over 2 hours on days 1 to 5, idarubicin 12 mg/m2 by 5 minute IV infusion on days 1 to 3, or topotecan 1.0 mg/m2 as an continuous IV infusion on days 1 to 5. Doses were then adjusted to define DLT for each combination.

Results: Eighty-seven patients (68 AML, eight MDS, 11 CML-BP) were treated. DLTs were hepatic transaminitis, hyperbilirubinemia, and hand foot syndrome (HFS) on the troxacitabine plus ara-C combination. The recommended phase II doses were 6 mg/m2 once a day for 5 days and 1.0g/m2 once a day for 5 days, respectively. DLTs were diarrhea, rash, and mucositis on the troxacitabine plus topotecan combination. The recommended phase II doses were 4 mg/m2 once a day for 5 days and 0.75 mg/m2 once a day for 5 days, respectively. DLTs were HFS, rash, and mucositis on the troxacitabine plus idarubicin combination. The recommended phase II doses were 4 mg/m2 once a day for 5 days and 9 mg/m2 once a day for 3 days, respectively. Among 74 evaluable patients with AML or MDS, 10 (13%) achieved complete remission and four (5%) had hematologic improvement. Two of 11 (18%) evaluable patients with CML-BP returned to chronic phase.

Conclusion: Troxacitabine-based combinations had significant antileukemic activity.
Docetaxel and Doxorubicin Compared With Doxorubicin and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer: Results of a Randomized, Multicenter, Phase III Trial
Authors: Nabholtz Jean-Marc , Falkson Carla , Campos Daniel , Szanto Janos , Martin Miguel , Chan Stephen , Pienkowski Tadeuz , Zaluski Jerzy , Pinter Tamas , Krzakowski Maciej , Vorobiof Daniel , Leonard Robert , Kennedy Ian , Azli Nacer , Murawsky Michael , Riva Alessandro , Pouillart Pierre
Published: March 2003

Purpose: This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC).

Patients and Methods: Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 (n = 214) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (n = 215) on day 1, every 3 weeks for up to eight cycles.

Results: Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank P = .014; median TTF, 25.6 v 23.7 weeks; log-rank P = .048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response [CR], 49% partial response [PR]) than for those taking AC (47%, with 7% CR, 39% PR) (P = .009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v 41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P < .001; 8% v 2%, P = .01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%).

Conclusion: AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.
Risk of Secondary Leukemia After a Solid Tumor in Childhood According to the Dose of Epipodophyllotoxins and Anthracyclines: A Case-Control Study by the Société Française d’Oncologie Pédiatrique
Authors: Le Deley Marie-Cécile , Leblanc Thierry , Shamsaldin Akthar , Raquin Marie-Anne , Lacour Brigitte , Sommelet Danièle , Chompret Agnès , Cayuela Jean-Michel , Bayle Chantal , Bernheim Alain , de Vathaire Florent , Vassal Gilles , Hill Catherine
Published: March 2003

Purpose: To estimate the risk of secondary leukemia as a function of the dose of epipodophyllotoxins and anthracyclines.

Methods: We conducted a case-control study of the risk of secondary leukemia or myelodysplasia after a solid tumor in childhood within the Société Française d’Oncologie Pédiatrique, including 61 patients with leukemia matched with 196 controls. The characteristics of the first cancer, the patient’s family history of cancer, and the treatment (type, cumulative dose of chemotherapy, schedule of etoposide administration, and radiation dose delivered to active bone marrow) were compared in the two groups.

Results: Only two factors were found to increase the risk of leukemia in multivariate analysis, namely, the type of the first tumor, with an excess risk in patients with Hodgkin’s disease (relative risk 6.4; 95% confidence interval [CI], 1.6 to 24) or osteosarcoma (relative risk 5; 95% CI, 1.3 to 19), and exposure to epipodophyllotoxins and anthracyclines. The risk of leukemia increased regularly with the cumulative dose of etoposide. In summary, patients who received between 1.2 and 6 g/m2 of epipodophyllotoxins or more than 170 mg/m2 of anthracyclines had a seven-fold higher risk (95% CI, 2.6 to 19) compared with patients who received lower doses or none of these drugs. The risk of leukemia in patients who received more than 6 g/m2 of epipodophyllotoxins was multiplied by 197 (95% CI, 19 to 2,058). The risk of leukemia was not increased by exposure to alkylating agents or radiotherapy.

Conclusion: Both epipodophyllotoxins and anthracyclines increase the risk of secondary leukemia. The current challenge is to minimize the mutagenic effects of these drugs by diminishing cumulative doses without losing the therapeutic benefits.
Multicenter Phase II Study of Oral Bexarotene for Patients With Metastatic Breast Cancer
Authors: Esteva Francisco J. , Glaspy John , Baidas Said , Laufman Leslie , Hutchins Laura , Dickler Maura , Tripathy Debu , Cohen Roger , DeMichele Angela , Yocum Richard C. , Osborne C. Kent , Hayes Daniel F. , Hortobagyi Gabriel N. , Winer Eric , Demetri George D.
Published: March 2003

Purpose: Bexarotene is a retinoid X receptor–selective retinoid that has preclinical antitumor activity in breast cancer. We evaluated the efficacy and safety of oral bexarotene in the treatment of patients with metastatic breast cancer.

Patients and Methods: The following three groups of patients were treated: hormone-refractory, chemotherapy-refractory, and tamoxifen-resistant patients. Patients in the first two groups were treated with bexarotene alone, whereas the tamoxifen-resistant patients received both tamoxifen and bexarotene. Patients in all groups were randomly assigned to receive bexarotene at either 200 or 500 mg/m2/d.

Results: One hundred forty-eight patients were randomized; 145 patients were treated. Of 48 hormone-refractory patients, there were two partial responses (6%) and 10 patients with stable disease lasting more than 6 months; of 47 chemotherapy-refractory patients, there were two partial responses (6%) and five patients with stable disease; and of 51 tamoxifen-resistant patients, there was one partial response (3%) and 11 patients with stable disease. All partial responses occurred at the 200-mg/m2/d dose. The projected median time to progression across all of the arms was 8 to 10 weeks. There were no drug-related deaths, and only two patients had drug-related serious adverse events. The most common drug-related adverse events were hypertriglyceridemia (84%), dry skin (34%), asthenia (30%), and headache (27%). There were no cases of pancreatitis.

Conclusion: The efficacy of bexarotene in patients with refractory metastatic breast cancer is limited. However, it is an oral agent with minimal toxicity and a unique mechanism of action, which produced clinical benefit in approximately 20% of patients. Future efforts should define populations likely to benefit from this agent.
Influenza Vaccination in Elderly Patients With Advanced Colorectal Cancer
Authors: Earle Craig C.
Published: March 2003

Purpose: To examine influenza vaccination use in patients undergoing chemotherapy for advanced cancer.

Methods: All Medicare patients treated for stage IV colorectal cancer between 1993 and 1998 while living in one of the regions monitored by the Survival, Epidemiology, and End Results Program who were alive in the fall months and who survived at least 4 months with their cancer were considered eligible to have received vaccination. Their medical bills were analyzed to determine receipt of influenza vaccination and subsequent outcomes.

Results: Eligibility criteria were met by 1,225 patients who were undergoing chemotherapy during 1,577 person-years of observation. Overall, 39.7% of patients received influenza vaccination, increasing from 26% in 1993 to 43% in 1998. When vaccination was administered, it was provided by primary care physicians 68% of the time. Vaccinated patients were more likely to be white, of higher socioeconomic status, and to have more comorbidity. Fewer diagnoses of influenza and pneumonia infections were made in vaccinated patients while undergoing treatment. Those patients who were immunized also had fewer chemotherapy interruptions and were more likely to survive through to the beginning of the next fall (hazard ratio, 0.88; 95% confidence interval, 0.77 to 0.99). There was a trend toward decreased resource use among immunized patients.

Conclusion: This study observed outcomes associated with influenza vaccination that are similar to those reported for patients without cancer. However, rates of immunization are relatively low, and disparities exist for vulnerable populations. As part of delivering high-quality care, oncologists should promote influenza vaccination for their patients who are undergoing treatment for advanced cancer.
Radiotherapy for Stages IIA/B Testicular Seminoma: Final Report of a Prospective Multicenter Clinical Trial
Authors: Classen Johannes , Schmidberger Heinz , Meisner Christoph , Souchon Rainer , Sautter-Bihl Marie-Luise , Sauer Rolf , Weinknecht Stefan , Köhrmann Kai-U. , Bamberg Michael
Published: March 2003

Purpose: A prospective multicenter trial was initiated to evaluate the role of modern radiotherapy with reduced treatment portals for stage IIA and IIB testicular seminoma.

Patients and Methods: Patients with stages IIA/B disease (Royal Marsden classification) were assessable for the trial. Staging comprised computed tomography of the chest, abdomen, and pelvis as well as analysis of tumor markers alpha-fetoprotein and beta human chorionic gonadotropin. Linac-based radiotherapy was delivered to para-aortic and high ipsilateral iliac lymph nodes. The total doses were 30 Gy for stage IIA and 36 Gy for stage IIB disease.

Results: Between April 1991 and March 1994, 94 patients were enrolled for the trial by 30 participating centers throughout Germany. Seven patients were lost to follow-up. Median time to follow-up of 87 assessable patients was 70 months. There were 66 stage IIA and 21 stage IIB patients. One mediastinal and one field-edge relapse were observed in the stage IIA group. In the stage IIB group, there was one mediastinal and one mediastinal/pulmonary relapse. All patients were treated with a salvage regimen of platinum-based chemotherapy. Actuarial relapse-free survival at 6 years was 95.3% (95% confidence interval [CI], 88.9% to 100%) and 88.9% (95% CI, 74.4% to 100%) for stage IIA and IIB groups, respectively. Maximum acute side effects were 8% grade 3 nausea for stage IIA and 10% grade 3 nausea and diarrhea for stage IIB groups. No late toxicity was observed.

Conclusion: Radiotherapy for stages IIA/B seminoma with reduced portals yields excellent tumor control at a low rate of acute toxicity and no late toxicity, which supports the role of radiotherapy as the first treatment choice for these patients.
Phase II, Randomized, Double-Blind Study of Two Dose Levels of Arzoxifene in Patients With Locally Advanced or Metastatic Breast Cancer
Authors: Buzdar Aman , O’Shaughnessy Joyce A. , Booser Daniel J. , Pippen John E. , Jones Stephen E. , Munster Pamela N. , Peterson Patrick , Melemed Allen S. , Winer Eric , Hudis Clifford
Published: March 2003

Purpose: To select a daily dose of arzoxifene ( LY353381 ), a selective estrogen receptor modulator, for use in future studies in women with locally advanced or metastatic breast cancer who are either potentially tamoxifen sensitive (TS) or tamoxifen refractory (TR).

Patients and Methods: This trial was a randomized, double-blind, phase II study of arzoxifene 20 mg (n = 55) and 50 mg (n = 57) in women with advanced or metastatic breast cancer. Patients were randomly assigned to balance for number of metastatic disease sites, prior tamoxifen therapy, and estrogen receptor status. The primary end point was tumor response rate (RR). Secondary end points included clinical benefit rate (CBR), time to progression (TTP), and toxicity.

Results: Forty-nine patients were TS and 63 were TR. According to independent review, among TS patients, RR was higher in the 20-mg arm than the 50-mg arm (26.1% v 8.0%), with a longer TTP (8.3 v 3.2 months; P > .05). Among the TR patients, response rate was the same in the 20-mg and 50-mg arms (10.3%) with similar TTP (2.7 and 2.8 months, respectively; P > .05). CBR was higher in the 20-mg arm than in the 50-mg arm among TS patients (39.1% v 20.0%) and TR patients (13.8% v 10.3%). Arzoxifene was well tolerated. Dose-dependent toxicity was not demonstrated. There were no deaths during study.

Conclusion: Arzoxifene is effective in the treatment of TS and TR patients with advanced or metastatic breast cancer at the 20-mg and 50-mg dose levels. Toxicities are minimal, and the therapy is tolerated. The 20-mg dose seems to be at least as effective as the 50-mg dose. Accordingly, arzoxifene 20 mg/d was selected for further study in patients with breast cancer.
Phase I and Pharmacokinetic Study of Intravenous Irinotecan Plus Oral Ciclosporin in Patients With Fluorouracil-Refractory Metastatic Colon Cancer
Authors: Chester John D. , Joel Simon P. , Cheeseman Susan L. , Hall Geoffrey D. , Braun Michael S. , Perry Jackie , Davis Theresa , Button Christopher J. , Seymour Matthew T.
Published: March 2003

Purpose: To assess the safety and toxicity profile of escalating doses of intravenous irinotecan, in combination with a fixed dose of oral ciclosporin (Cs) and to determine the pharmacokinetic profile of irinotecan and its metabolites.

Patients and Methods: Patients with fluorouracil-refractory metastatic colorectal cancer received escalating doses of intravenous irinotecan from 40 to 125 mg/m2 every 2 weeks in combination with a fixed dose of oral Cs (5 mg/kg bid for 3 days). Pharmacokinetic analysis of plasma irinotecan and its metabolites SN38 and SN38G was performed during paired cycles with and without Cs.

Results: Thirty-seven patients were treated. Dose-limiting toxicity of grade 4 neutropenia was seen at an irinotecan dose of 125 mg/m2. There was no grade 4 diarrhea, and only one patient experienced grade 3 diarrhea. Toxicities caused by Cs were generally mild. Pharmacokinetic studies demonstrated that irinotecan clearance was reduced from 13.4 to 5.8 L/h/m2 and area under the curve (AUC)0-tn was increased 2.2-fold by the coadministration of Cs. Similar significant increases in AUC0-24h were seen for both SN38 and SN38G (2.2-fold and 2.3-fold, respectively) in the presence of Cs. Antitumor activity was seen at every irinotecan dose level.

Conclusion: The maximum tolerated irinotecan dose and recommended dose for phase II studies is 100 mg/m2 every 2 weeks. Dose-limiting diarrhea was not seen during this study, supporting the hypothesis that pharmacokinetic modulation of irinotecan by Cs may improve its therapeutic index. Further studies using this combination are warranted.
Cytokine-Hormone Interactions: Tumor Necrosis Factor α Impairs Biologic Activity and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts
Authors: Broussard Suzanne R. , MCCusker Robert H. , Novakofski Jan E. , Strle Klemen , Hong Shen Wen , Johnson Rodney W. , Freund Gregory G. , Dantzer Robert , Kelley Keith W.
Published: March 2003

TNFα is elevated following damage to skeletal muscle. Here we provide evidence that TNFα acts on muscle cells to induce a state of IGF-I receptor resistance. We establish that TNFα inhibits IGF-I-stimulated protein synthesis in primary porcine myoblasts. Similar results were observed in C2C12 murine myoblasts, where as little as 0.01 ng/ml TNFα significantly inhibits protein synthesis induced by IGF-I. TNFα also impairs the ability of IGF-I to induce expression of a key myogenic transcription factor, myogenin. The inhibition by TNFα of IGF-I-induced protein synthesis and expression of myogenin is not due to direct killing of myoblasts by TNFα. Although IGF-I induces an approximately 19-fold induction in tyrosine phosphorylation of the β-chains of its receptor, TNFα does not inhibit this autophosphorylation. Instead, TNFα significantly reduces by approximately 50% IGF-I-stimulated tyrosine phosphorylation of two of the major downstream receptor docking molecules, insulin receptor substrate (IRS)-1 and IRS-2. These results establish that low picogram concentrations of TNFα acts on both porcine and murine myoblasts to impair tyrosine phosphorylation of both IRS-1 and IRS-2, but not the receptor itself. These data are consistent with the notion that very low physiological concentrations of TNFα interfere with both protein synthesis and muscle cell development by inducing a state of IGF-I receptor resistance.
Dynamic behavior of a combined cycle power plant in the presence of a frequency drop
Authors: Baba Kazuhiro , Kakimoto Naoto
Published: March 2003

A combined cycle power plant which combines a gas turbine and a steam turbine can achieve high energy efficiency. Many combined cycle plants have been installed worldwide. However, a large‐scale blackout due to combined cycle chain trip‐out occurred in Malaysia in 1996. The cause of this chain trip was considered to be a large drop of system frequency. Thus, there is a need to investigate the stability of the combined cycle power plant for the frequency drop. Several dynamic models of a combined cycle plant have been proposed. In our analysis, we use some of them and build a model for a single‐shaft combined cycle plant. We execute numerical simulations to see how the combined cycle plant behaves when the system frequency drops. The cause and the countermeasure of the combined cycle plant trip‐out are explained. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(3): 9–19, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10117
Automatic generation of system descriptions for plant supervisory control systems
Authors: Nakata Hideo , Harauchi Satoshi , Kojima Taizo
Published: March 2003

This paper describes the automatic generation of system descriptions for SCADA (Supervisory Control And Data Acquisition) systems. The proposed method produces various types of data and programs for SCADA systems from equipment definitions using conversion rules. First, it makes directed graphs, which represent connections between the equipment, from equipment definitions. System descriptions are generated using the conversion rules, by analyzing these directed graphs, and finding groups of equipment that involve similar operations. This method can be used with various SCADA systems, and provides visual tools for editing conversion rules. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(3): 29–37, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10149
“Pulsed field losses and coupling current loop in a large‐current superconductor”, Electrical Engineering in Japan Volume 142, Number 4, 2003, pages 27–33
Authors: Shimamoto Susumu , Murase Satoru , Nishii Kenji , Naitou Fuminobu , Matsui Kunihiro , Takahashi Yoshikazu , Tsuji Hiroshi
Published: March 2003

The original article to which this Erratum refers was published in Electrical Engineering in Japan, Volume 142, Number 4, 2003, pages 27–33

An error appeared in the above article. The affiliations are correct as here. We apologize for any inconvenience this error may have caused.
The role of armadillos in the movement of archaeological materials: An experimental approach
Authors: Araujo Astolfo G. Mello , Marcelino José Carlos
Published: March 2003

Armadillos are medium‐sized animals whose burrowing behavior can be significant in archaeological settings ranging from South America to the central United States. Although archaeologists are well aware that these animals can move archaeological materials across stratigraphic layers, few data are available about the magnitude of mixing, number of burrows per individual, dimension of burrows, and their impact on archaeological sites. This paper addresses the problem from an experimental perspective. Specifically, we monitored the action of the yellow armadillo (Euphractus sexcintus) in translocating cultural materials. Our results suggest that: (1) the vertical movement of artifacts has no preferential direction; (2) cultural horizons at least 20 cm apart can be mixed; (3) the animal's activity leaves some distinct traces that can be recognized during an excavation; and (4) there is no significant correlation between size, shape, or weight of artifacts and amount of displacement. © 2003 Wiley Periodicals, Inc.
Public funding for residential and nursing home care: projection of the potential impact of proposals to change the residential allowance in services for older people
Authors: Clarkson Paul , Hughes Jane , Challis David
Published: March 2003

Background

This paper investigates the potential effects of a policy change in the funding of UK residential care. The White Paper Modernising Social Services (Cm 4169, 1998) outlined plans to change the distribution of the Residential Allowance (RA), payable in support of residents in independent residential or nursing home care, from a component of income support paid direct to establishments to a grant to local authorities. This change was intended to remove the perverse incentive in accessing independent residential care more favourably than local authority care. A further objective was to encourage local authorities to use the grant to support home‐based alternatives to residential care. The policy rests on a model in which price signals dictate the choice of care for an older person. By, in effect, raising the price of independent residential and nursing home care, the policy provides an incentive for authorities to seek alternatives to institutional care.

Methods

Managers from 16 UK social services departments attended a focus group discussion, completed questionnaires and provided information to assist in calculating the potential diversionary effect of the policy.

Results

Managerial estimates indicated a small diversionary effect of the policy; A potential effect of 0.26 and 0.19 per 1000 older people diverted from residential and nursing care respectively.

Conclusions

The study indicated that wider organisational factors other than price are likely to play a greater role in deciding whether an older person is admitted to care. Changes in public funding alone do not reflect the complexities involved in decision‐making concerning the residential placement of older people. Copyright © 2003 John Wiley & Sons, Ltd.
The cost implications of the changing population and characteristics of care homes
Authors: Darton Robin , Netten Ann , Forder Julien
Published: March 2003

Background

Recent increases in care home closures suggest that homes may not be able to balance pressures to reduce costs against pressures to increase standards. Commissioning requires an understanding of the factors affecting costs and how they change over time.

Methods

A survey of care homes for older people was conducted in 21 local authorities in England in 1996. A complete response was obtained for 618 homes (75%) and 11,900 residents. Findings were compared with surveys conducted in 1986 and 1988.

Results

Dependency was significantly related to prices, primarily due to the differential payments to nursing and residential homes. Home characteristics were also related to price, the proportion of single rooms having the largest impact. However, prices were most sensitive to local wage rates, particularly in residential homes. Compared with previous surveys levels of dependency had increased, particularly in voluntary residential homes and nursing homes. Independent homes were more likely to be purpose built, and a higher proportion of beds were in single rooms, although only 30% of private residential, dual registered and nursing homes achieved the proposed level of 80% of beds in single rooms. Staffing ratios appeared to have increased, but price rises were modest, particularly for nursing homes.

Conclusions

Standards of provision have improved over time, although prices appear to have been kept below those expected from increases in costs. Continuing pressures on costs and prices are likely to lead to further closures and a restriction of choice for older people. Copyright © 2003 John Wiley & Sons, Ltd.
The role of the specialist physician in nursing homes: the Netherlands' experience
Authors: Frank Hoek J. , Ribbe Miel W. , Hertogh Cees M. P. M , van der Vleuten Cees P. M.
Published: March 2003

Background

Dutch nursing homes employ physicians who have completed a two year specialist training programme to become a qualified nursing home physician. This paper describes the origin of the profession of nursing home medicine in the context of Dutch nursing homes.

Method

Review of the history and development of the need for specialist physicians in care of residents in nursing homes. Examination of the competencies required and training available for physicians and the benefits of this arrangement in improving quality of care.

Results

Relevant skills and competencies of the specialist physician in nursing homes are discussed. The role and tasks, and the nursing home physician's method of working and providing care are explained, as well as the benefits and disadvantages of organizing medical care in this way.

Conclusions

The benefits of a specialist physician are considered greater than the disadvantages. Specialist training for this role is considered to be highly desirable. Copyright © 2003 John Wiley & Sons, Ltd.
International experiments in integrated care for the elderly: a synthesis of the evidence
Authors: Johri Mira , Beland Francois , Bergman Howard
Published: March 2003

Background

The OECD countries have recently promoted policies of deinstitutionalisation and community‐based care for the elderly. These policies respond to common cost pressures associated with population aging, and the challenge of providing improved care for the elderly. They aim to substitute less costly services for institutional ones, to improve patient satisfaction and decrease expenses. However, views concerning their success are mixed. We took a comparative cross‐national approach to examine the evidence, to identify common features of an effective system of integrated care, and to examine the potential of such models to positively affect care of the elderly, and public finances.

Methods

We conducted a systematic review of recent demonstration projects testing innovative models of care for the elderly in OECD countries. Projects included aimed to create comprehensive integration of acute and long‐term care services, and were evaluated using a comparison group.

Results

For each project, we report available results on rates of hospitalisation, long term care institutionalisation, utilisation and costs, impact on process of care, and health outcomes. In addition, the following common features of an effective integrated system of care were identified: a single entry point system; case management, geriatric assessment and a multidisciplinary team; and use of financial incentives to promote downward substitution.

Conclusions

Community‐based care can impact favourably on rates of institutionalisation and costs. Comprehensive approaches to program restructuring are necessary, as cost‐effectiveness depends on characteristics of the system of care. Expansion of successful programmes to achieve widespread use remains a critical challenge. Copyright © 2003 John Wiley & Sons, Ltd.
Improving nursing home quality of care through outcomes data: the MDS quality indicators
Authors: Zimmerman David R.
Published: March 2003

Background

The quality of care provided to nursing home residents is a continuing source of concern throughout the world. In the United States, the Health Care Financing Administration mandated the use of a standardised resident assessment instrument, called the Minimum Data Set (MDS) which facilitated the development of a set of nursing home quality of care indicators.

Methods

The MDS Quality Indicators were developed by a team of researchers at the University of Wisconsin‐Madison and covered 12 domains, as well as associated risk factors. This initial set of indicators then went through an iterative process of review by national clinical panels, further empirical analysis, validation studies, and pilot tests, to confirm whether they were accurate, reliable and useful tools for identifying quality problems.

Results

The final set of MDS Quality Indicators includes 24 variables that include both processes and outcomes of care and prevalence and incidence measures. They are defined at both the resident and facility level. Four of the indicators are risk‐adjusted.

Conclusion

The indicators have several possible applications: a source of consumer information; to help guide policy makers; and to assist providers in conducting quality improvement initiatives and to evaluate the impact of these efforts. Copyright © 2003 John Wiley & Sons, Ltd.
Benchmarking and quality in residential and nursing homes: lessons from the US
Authors: Mor Vincent , Angelelli J. , Gifford D. , Morris J. , Moore T.
Published: March 2003

Background

Performance measurement and benchmarking are common concerns in the delivery of long term care. It is common to measure the performance of providers and to publicly report these data. This paper examines selected technical challenges facing those who design, implement and disseminate health care quality performance measures.

Method

Review of the application of measures of performance in the US nursing home sector.

Results

Using examples drawn from the skilled nursing home arena, problems ranging from data reliability and validity, the multi‐dimensional nature of quality measures and selection bias as well as differential measurement abilities are discussed.

Conclusions

Benchmarking of performance is an inherently complex issue. However, to ensure that such comparisons are both fair and valid requires measures to be more technically sophisticated and sensitive to real changes attributable to changes in care. Copyright © 2003 John Wiley & Sons, Ltd.