bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractTNFα 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.