bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk non-T, non-B acute lymphocytic leukemia: A Pediatric Oncology Group study.
Authors: Camitta B , Mahoney D , Leventhal B , Lauer S J , Shuster J J , Adair S , Civin C , Munoz L , Steuber P , Strother D 
Published: February 2017

PURPOSE To determine the potential efficacy and toxicity of intravenous (i.v.) methotrexate (MTX) and mercaptopurine (MP) as postremission intensification treatment for children with B-lineage acute lymphoblastic leukemia (ALL) at higher risk to relapse. PATIENTS AND METHODS Eighty-three patients (age 1 to 20 years) with higher-risk B-lineage ALL were entered onto this protocol. Following standard four-drug remission induction, 80 patients received 12 intensive 2-week cycles of MTX/MP: MTX 200 mg/m2 i.v. push, then 800 mg/m2 i.v. 24-hour infusion on day 1; MP 200 mg/m2 i.v. in 20 minutes, then 800 mg/m2 i.v. 8-hour infusion day 2; MTX 20 mg/m2 intramuscularly day 8; and MP 50 mg/m2 by mouth days 8 to 14. Age-based triple intrathecal therapy (MTX, hydrocortisone, and cytarabine) was administered for CNS prophylaxis. Continuation therapy was weekly MTX/MP (as on days 8 to 14) for 2 years. RESULTS Eighty-one patients (98%) entered remission. There were 28 relapses (marrow, n = 11; marrow and CNS, n = 2; isolated CNS, n = 9; testes, n = 5; ovaries, n = 1). No overt relapse occurred during the intensive phase of therapy. The event-free survival (EFS) rate at 4 years is 57.4% +/- 9.1% (SE). Hematologic, mucosal, and infectious toxicities were seen in 12%, 9%, and 5% of intensive MTX/MP courses, but were generally mild. CONCLUSION Combined data from this and our previous trial suggest that intensive MTX/MP may produce long-term disease-free survival in 70 to 75% of children with B-lineage ALL. In comparison to other intensive regimens, intensive MTX/MP is easy to administer, effective, and relatively nontoxic. If patients at risk for failure of MTX/MP can be identified prospectively, more aggressive regimens could be restricted to this smaller (25% to 30%) cohort.
Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up.
Authors: Schultz P K , Herr H W , Zhang Z F , Bajorin D F , Seidman A , Sarkis A , Fair W R , Scherr D , Bosl G J , Scher H I 
Published: February 2017

PURPOSE To determine survival in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and to analyze prechemotherapy and postchemotherapy factors for prognostic significance. PATIENTS AND METHODS The survival of 111 patients with T2-4N0M0 bladder cancer treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was assessed. Prechemotherapy and postchemotherapy factors were analyzed for correlation with survival. Factors found to be significant on univariate analysis were subjected to multivariate analysis using Cox's proportional hazards model. RESULTS The median follow-up duration was 5.3 years. Initial tumor (T) stage (P = .0001), presence of ureteral obstruction (P = .0074), and presence of a palpable mass (P = .0039) were the only pretreatment factors found to be significant on univariate analysis. Postchemotherapy surgery was performed in 81 patients. In these cases, postchemotherapy clinical stage and pathologic stage were significant factors on univariate analysis. In the multivariate analysis, the initial prechemotherapy T stage and the postchemotherapy pathologic stage (pT stage) were the only two factors to demonstrate independent significance. An association between downstaging postchemotherapy and survival was observed for patients with extravesical disease (T < or = 3B) at the start of treatment. In this subset, the 5-year survival rate was 54% for patients with downstaging versus 12% for those without downstaging. This association was not observed for patients with bladder-confined disease (T < or = 3A) at presentation. CONCLUSION The stage of bladder cancer at presentation and at postchemotherapy pathologic staging are independent prognostic factors for long-term survival in patients treated with neoadjuvant chemotherapy. Downstaging after neoadjuvant chemotherapy was associated with improved survival in patients with muscle-invasive bladder cancers, but only for those with extravesical disease (T > or = 3B) pretreatment. Randomized comparisons will be required to assess the impact of chemotherapy on overall survival.
Incidence of multiple myeloma in Olmsted County, Minnesota: 1978 through 1990, with a review of the trend since 1945.
Authors: Kyle R A , Beard C M , O'Fallon W M , Kurland L T 
Published: February 2017

PURPOSE Incidence rates of multiple myeloma appear to have increased in recent decades, but it is difficult to compare the incidence rates over time because of changes in laboratory procedures, differences in diagnostic criteria, and variations in indexing of medical records. However, Olmsted County, Minnesota, provides a rare opportunity to minimize these limitations, because the medical care has been provided mainly by the Mayo Clinic. PATIENTS AND METHODS Records of Olmsted County residents with a diagnosis of multiple myeloma from January 1, 1978 through December 31, 1990 were reviewed. Criteria for diagnosis and residency were the same as in previous Olmsted County studies. RESULTS The incidence rate per 100,000 age-adjusted to the 1950 United States white population was 5.4 for males and 2.8 for females; the overall rate was 4.1. The rates were age-adjusted to the 1950 United States population for comparison with earlier data from this population. The rates increased with age for both sexes. There was no significant change in incidence rates from 1945 through 1990. A comparison of the median age for Olmsted County patients with the age of those referred to the Mayo Clinic from elsewhere indicated that the local patients were appreciably older (74 v. 62 years, respectively). Thirty-two of 55 patients (58%) with multiple myeloma from 1978 through 1990 had a monoclonal plasma-cell proliferative process before the diagnosis of multiple myeloma. CONCLUSION The incidence rate of multiple myeloma in Olmsted County, Minnesota, has not changed significantly during the past 46 years. We believe that reports of increasing rates over time are mainly due to improved case ascertainment.
Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study.
Authors: Muss H B , Case L D , Atkins J N , Bearden J D , Cooper M R , Cruz J M , Jackson D V , O'Rourke M A , Pavy M D , Powell B L 
Published: February 2017

PURPOSE To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting. PATIENTS AND METHODS Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown. RESULTS One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen. CONCLUSION In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.
Plasminogen activator inhibitor-1 and prognosis in primary breast cancer.
Authors: Foekens J A , Schmitt M , van Putten W L , Peters H A , Kramer M D , Jänicke F , Klijn J G 
Published: February 2017

PURPOSE Evaluation of the relationship between plasminogen activator inhibitor-1 (PAI-1) and the metastatic potential of primary breast cancer, and to compare the prognostic impact of PAI-1 in multivariate analysis with those of conventional prognostic factors, including steroid-hormone receptors, and those of urokinase plasminogen activator (uPA), pS2-protein (PS2), and cathepsin D. PATIENTS AND METHODS Cell biologic prognostic factors were analyzed in 657 cytosols routinely prepared from frozen-tissue biopsies that were submitted to our laboratory for the assessment of steroid-hormone receptor status. The median duration of follow-up in patients still alive at the time of analysis was 48 months. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assay, PS2, and cathepsin D by radiometric immunoassay, and uPA and PAI-1 by enzyme-linked immunosorbent assay (ELISA). RESULTS PAI-1 levels were found to be strongly positively correlated with the rates of relapse (P < .0001) and death (P < .001). Relating the levels of PAI-1 with those of other cytosolic prognostic factors, we found a positive association with the metastasis-related proteases uPA (P < .0001) and cathepsin D (P < .0001). On the other hand, PAI-1 levels were found to be negatively correlated with ER (P < .005) and PgR (P < .001), and the estrogen-regulated pS2-protein (P < .001), which are proteins associated with a favorable prognosis. In multivariate regression analysis for 5-year relapse-free survival, and using an optimized cutoff point for discrimination between PAI-1-positive and -negative, independent predictors of the rate of relapse were found to be PAI-1 (P < .0001) and uPA (P = .01) of the cytosolic parameters, and tumor size, lymph node status, and premenopausal age of the clinical parameters. In multivariate analysis in patients with node-negative disease, only PAI-1 (P < .001) and tumor size (P = .03) were positively and premenopausal age negatively (P < .001) associated with the rate of relapse. In patients with node-positive disease, PAI-1 (P < .001), uPA (P = .02), tumor size (P < .001), and the number of positive lymph nodes (P < .001) were all positively associated with the rate of relapse. CONCLUSION We conclude that the PAI-1 level measured in routinely prepared cytosols is an important parameter to predict the metastatic potential in both node-negative and node-positive human primary breast cancer.
Leukemia: management of relapse after allogeneic bone marrow transplantation.
Authors: Kumar L 
Published: February 2017

PURPOSE To review the current state of knowledge regarding the management of leukemic relapse after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS The literature was analyzed using MEDLINE (National Library of Medicine, Bethesda, MD) and reports were identified through review of report bibliographies. Pertinent studies were selected and data synthesized into a review format. RESULTS Leukemic relapse after allogeneic BMT is an important cause of treatment failure. The risk of leukemic relapse varies from 20% to 60% depending on the diagnosis and phase of disease. Reinduction chemotherapy (CT), second BMT, interferon (IFN) alfa, and donor leukocyte infusions are various options, but none of the approaches is clearly optimal. Approximately 50% of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients achieve remission after standard induction CT. However, most patients finally relapse and die of uncontrolled leukemia. Second BMT is successful in 20% to 25% patients and is a reasonable option in patients who relapse more than 6 months after the initial transplant. Young patients with a good performance status and those in remission from initial transplant relapse have a better outcome after second BMT. Venocclusive disease (VOD), interstitial pneumonitis (IP), and acute graft-versus-host disease (GVHD) are the main complications. Therapy with IFN alfa results in cytogenetic complete remission (CR) in 10% to 25% patients with chronic myeloid leukemia (CML). The initial results of leukocyte infusions from the original donor are promising. However, acute GVHD and bone marrow aplasia are associated complications. The correct dose and schedule of donor leukocyte infusions need to be determined in future studies to minimize GVHD while maintaining the graft-versus-leukemia (GVL) effect. CONCLUSION Identification of patients at increased risk for relapse and use of biologic response modifiers post-transplant to augment the GVL effect in such patients are possible areas of improvement for future studies.
Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study.
Authors: Thigpen J T , Blessing J A , Ball H , Hummel S J , Barrett R J 
Published: February 2017

PURPOSE This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy. PATIENTS AND METHODS Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol. RESULTS Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (< 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each. CONCLUSION Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.
Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial.
Authors: Wishart G C , Bissett D , Paul J , Jodrell D , Harnett A , Habeshaw T , Kerr D J , Macham M A , Soukop M , Leonard R C 
Published: February 2017

PURPOSE To evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer. PATIENTS AND METHODS Between 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses. RESULTS Ten eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anthracycline resistance in multidrug-resistant (MDR) breast carcinoma cells in vitro. There were no statistically significant differences in hematologic or gastrointestinal toxicity between the two arms. The response rate in the placebo arm was 44% (6% complete remission [CR], 38% partial remission [PR]), and in the quinidine arm was 43% (4% CR, 39% PR). Surviving patients have been monitored for a median time of 74 weeks, and there is no significant difference in the overall or progression-free survival between the two arms. The median survival times were 59 weeks for placebo and 47 weeks for quinidine patients. The estimated relative death rate (quinidine/placebo) was 1.2 (P = .247; 95% confidence interval [CI], 0.88 to 1.63). CONCLUSION Quinidine at this dose does not significantly alter the toxicity profile, response rate, or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin.
Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report.
Authors: Hussain M , Wolf M , Marshall E , Crawford E D , Eisenberger M 
Published: February 2017

PURPOSE To assess the impact of prognostic factors, including continued (orchiectomy) versus discontinued androgen-suppression (nonorchiectomy) therapy, on chemotherapy response and survival of patients with hormone-refractory prostate cancer. METHODS Analysis of five consecutive Southwest Oncology Group (SWOG) phase II chemotherapy trials was undertaken. RESULTS Two hundred five hormone-refractory patients were evaluated. Eighty-four percent had been orchiectomized. The median survival durations for the nonorchiectomy and orchiectomy patients were 6 and 7 months, respectively (P = .73). In a univariate analysis, orchiectomy patients had a significantly longer median time from diagnosis to first hormone therapy (1.1 v 0.1 years, P = .003), were more likely to have had chemotherapy initiated > or = 2 years from diagnosis (75% v 56%, P = .03), had a lower incidence of liver metastases (16% v 30%, P = .05), and had lower likelihood of being black (8% v 18%, P = .05) when compared with the nonorchiectomy group. Orchiectomy patients had a marginally significant longer median time from initial hormone treatment, more prior endocrine manipulations, lower median baseline alkaline phosphatase levels, and a lower likelihood of response to chemotherapy when compared with the nonorchiectomy group. Absence of liver metastases (P = .004), hemoglobin level > or = 10 g/dL (P < .001), acid phosphatase level > or = 1.2 IU/L (P = .05), response to chemotherapy (P = .001), and > or = 2 years from initial hormone treatment (P = .01) are important factors for survival. CONCLUSION This study failed to show obvious advantages in response to chemotherapy or survival for patients with continued gonadal suppression. A prospective randomized trial is suggested to evaluate the effect of this factor on progression-free and overall survival of patients with hormone-refractory prostate cancer receiving chemotherapy.
Improved survival for patients with AIDS-related Kaposi's sarcoma.
Authors: Miles S A , Wang H , Elashoff R , Mitsuyasu R T 
Published: February 2017

PURPOSE We retrospectively analyzed all patients with AIDS-related Kaposi's sarcoma (AIDS-KS) seen at one large California medical center to delineate factors that may have contributed to a relative decline in survival. METHODS Potential prognostic factors were analyzed individually, using the Cox proportional hazards regression model, for their association with survival. After a stepwise Cox regression procedure was applied to those factors that showed a significant effect on survival, a subset of factors that best predicted survival was identified. We then quantified the effect of the year of diagnosis on survival using a univariate Cox model. Next, we combined the year of diagnosis with the subset of prognostic factors previously identified into the Cox model to examine survival after adjustment for the prognostic factors. Survival distribution was estimated by the Kaplan-Meier method, and the 95% confidence interval for the median survival was computed using the modified reflected method. RESULTS In 688 patients, we identified four baseline variables that best predicted survival: CD4 cell number, hematocrit, number of KS lesions, and body mass index (BMI). Adjusted for these predictive factors, there was a significant improvement in survival for patients with AIDS-KS over the last 6 years. CONCLUSION Contrary to prior reports, survival has increased for patients with AIDS-KS. The apparent increase in observed mortality is most likely due to a decline in the CD4 cell number at presentation.
Effect of body position on ventricular CSF methotrexate concentration following intralumbar administration.
Authors: Blaney S M , Poplack D G , Godwin K , McCully C L , Murphy R , Balis F M 
Published: February 2017

PURPOSE Intralumbar methotrexate is one of the primary therapeutic modalities for the prevention and treatment of meningeal leukemia. However, methotrexate distribution to the ventricles is limited and highly variable following intralumbar dosing, and cytotoxic concentrations of methotrexate are not always achieved or sustained in the ventricular CSF. We used a nonhuman primate model to determine the effect of body position on the caudal distribution of an intralumbar dose of methotrexate. METHODS Methotrexate (1.0 mg) was administered by intralumbar injection to four animals, which were then immediately placed either in an upright sitting position or in a prone position for 1 hour, then upright. Each animal served as its own control and was studied in each position on at least one occasion. RESULTS The mean peak ventricular methotrexate concentration was 0.12 mumol/L (range, 0.091 to 0.20) in animals that were immediately placed upright, compared with 2.81 mumol/L (range, 0.21 to 8.9) in animals that remained prone for 1 hour. The mean area under the concentration-versus-time curves (AUC) was 0.51 mumol/L.h (range, 0.26 to 1.1) in the upright animals and 12.0 mumol/L.h (range, 0.9 to 35.4) in the prone animals. CONCLUSION Maintaining a prone position for 1 hour after an intralumbar dose increased the peak methotrexate concentration and drug exposure in ventricular CSF. CSF drug distribution following intralumbar therapy can be influenced by body position after the injection.