bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of a novel assay for breast cancer mucin to CA15-3 and carcinoembryonic antigen.
Authors: Daly L , Ferguson J , Cram G P , Hars V , George S L , McCarty K S , Bast R C 
Published: February 2017

PURPOSE To compare the sensitivity and specificity of an automated microparticle enzyme immunoassay (MEIA) for breast cancer mucin (IMx BCM; Abbott Laboratories, North Chicago, IL) to that of CA15-3 and carcinoembryonic antigen (CEA) for detecting and monitoring breast cancer. MATERIALS AND METHODS IMxBCM was compared to assays of CA15-3 and CEA in 630 serum specimens from healthy women, and from women with breast cancer, other malignancies, benign breast conditions, or other benign diseases. RESULTS Analysis of the log-transforms for the three markers in all specimens showed a high correlation of IMxBCM with CA15-3 (r = .78), but not with CEA (r = .25). Based on a receiver-operating-characteristics (ROC)-curve analysis for any given specificity, IMxBCM was found to be a more sensitive marker than either CA15-3 or CEA for distinguishing 105 women with advanced or metastatic breast cancer from 89 healthy women (P = .003 and P = .04, respectively), from 98 women with benign breast conditions (P = .02 and P = .002), or from 191 women with benign diseases (P = .03 and P less than .0001). At 95% specificity, the sensitivities of IMxBCM, CA15-3, and CEA for detecting advanced or metastatic breast cancer were 69%, 51%, and 30%, respectively. Serial serum samples (n = 177) were analyzed in 20 additional metastatic breast cancer patients with measurable disease. Serial IMxBCM levels corresponded with the clinical course of disease in 80%, CA15-3 in 65%, and CEA in 60% of the 20 patients. CONCLUSIONS Increased sensitivity of IMxBCM, despite a high correlation with CA15-3, suggests that IMxBCM and CA15-3 may recognize distinct epitopes on the same molecule. Although further research is indicated, IMxBCM may provide a promising marker in the clinical management of breast cancer patients.
Effects of recombinant human interleukin-3 in patients with relapsed small-cell lung cancer treated with chemotherapy: a dose-finding study.
Authors: Postmus P E , Gietema J A , Damsma O , Biesma B , Limburg P C , Vellenga E , de Vries E G 
Published: February 2017

PURPOSE The aim of the study was to determine the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after combination chemotherapy and to evaluate the ability of rhIL-3 to influence hematopoietic recovery. PATIENTS AND METHODS Nineteen patients who had relapsed small-cell lung cancer (SCLC) received rhIL-3 after their second course of chemotherapy, which consisted of either cyclophosphamide, doxorubicin, and etoposide (CDE) every 3 weeks or vincristine, ifosfamide, mesna, and carboplatin (VIMP) every 4 weeks. Twenty-four hours after the last chemotherapy dose, rhIL-3 was administered subcutaneously (SC) once daily for 14 days on an outpatient basis. Escalating dosages (1, 2, 4, 8, and 16 micrograms/kg/d) of rhIL-3 were tested. Hematologic effects were evaluated by comparing blood cell recovery after chemotherapy cycle 1 and cycle 2 plus rhIL-3. RESULTS The adverse effects of rhIL-3 at dosages up to 8 micrograms/kg/d consisted mainly of low-grade fever and flulike symptoms. At 16 micrograms/kg, rhIL-3 headache became dose-limiting. Severe neutropenia (neutrophils less than 0.5 x 10(9)/L) after VIMP cycle 2 was shorter in duration than after cycle 1 (7 v 3 days; P less than .05). At rhIL-3 dose levels 8 and 16 micrograms/kg, hematologic effects in seven patients who were treated with VIMP showed a significant hastened recovery of leukocyte and neutrophil counts during cycle 2 compared with cycle 1 and increased monocyte and eosinophil counts in cycle 2 compared with cycle 1. rhIL-3 also increased reticulocyte and platelet counts at a dose level of 8 micrograms/kg. No significant stimulation of basophils and lymphocytes was observed. Apart from the hematologic effects, rhIL-3 also augmented the release of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and lowered cholesterol levels. CONCLUSIONS This study demonstrates that rhIL-3 can be safely administered after chemotherapy on an outpatient basis. rhIL-3 is tolerated well at doses up to 8 micrograms/kg/d and is biologically active in patients after myelosuppressive chemotherapy.
Influence of sex and age on fluorouracil clearance.
Authors: Milano G , Etienne M C , Cassuto-Viguier E , Thyss A , Santini J , Frenay M , Renee N , Schneider M , Demard F 
Published: February 2017

PURPOSE Currently, fluorouracil (5-FU) is one of the major drugs used in cancer chemotherapy. Several investigators, including ourselves, have demonstrated a link between abnormalities in 5-FU clearance (Cl) and the risk of developing more or less 5-FU-related toxicities. Age and sex are among the host factors that have been implicated in the pharmacokinetic variability of drugs. Presently, no data are available on the possible influence of sex and age on 5-FU Cl. PATIENTS AND METHODS Three hundred eighty patients (mean age, 61.7 years; range, 25 to 91; 301 men and 79 women) with squamous cell carcinoma (sre) of the head and neck were treated in our institution between 1987 and 1991. 5-FU Cl was determined for a total of 1,092 chemotherapy cycles. Each cycle consisted of cisplatin and 5-day continuous intravenous infusion 5-FU (daily doses ranging between 365 and 1,224 mg/m2). RESULTS 5-FU Cl values (L/h/m2) showed a wide dispersion for both men (median, 179; range, 29 to 739) and women (median, 155; range, 56 to 466). 5-FU Cl values were lower significantly for women compared with men (P = .0005). When adjusted for age and dose, the influence of sex on log Cl remained significant (P = .013). There was no evidence that age modified 5-FU Cl when adjusted for sex and dose. Interestingly, for both men and women, the oldest patients (greater than 70 years) maintained their ability to clear 5-FU with daily doses that ranged from 500 to 1,000 mg/m2. CONCLUSIONS These data indicate that the capacities to clear 5-FU are lower in women compared with men and are not influenced by age. It would be of interest to know whether this sex-related difference in 5-FU Cl may be clinically relevant by considering both toxicity and tumor response to 5-FU treatment.
Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach.
Authors: Minsky B D , Cohen A M , Kemeny N , Enker W E , Kelsen D P , Reichman B , Saltz L , Sigurdson E R , Frankel J 
Published: February 2017

PURPOSE We compared the combined radiation therapy (RT) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT, fluorouracil (5-FU), and high-dose leucovorin (LV) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer. PATIENTS AND METHODS Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5-FU. Patients with resectable disease received identical doses, techniques, and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively. On day 1, patients received LV and 5-FU times one cycle. RT began on day 8. A second cycle of LV and 5-FU was given concurrently with the fourth week of RT. RESULTS Although more patients (75% v 32%; P = .02) received the higher dose level of 5-FU (250 mg/m2), significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy (13% v 48%; P = .045). There was no grade 3 to 4 myelosuppression in either group. The two grade 3 toxicities in the preoperative group were gastrointestinal. The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary; four patients had a grade 4 toxicity. CONCLUSION Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach.
Methotrexate pharmacokinetics following administration of recombinant carboxypeptidase-G2 in rhesus monkeys.
Authors: Adamson P C , Balis F M , McCully C L , Godwin K S , Poplack D G 
Published: February 2017

PURPOSE Carboxypeptidase-G2 (CPDG2) is a bacterial enzyme that rapidly hydrolyzes methotrexate (MTX) into inactive metabolites. As an alternative form of rescue after high-dose MTX (HDMTX), CPDG2 has more potential advantages than standard leucovorin (LV) rescue. In this study, the plasma pharmacokinetics of MTX with and without CPDG2 were evaluated in adult rhesus monkeys. MATERIALS AND METHODS The plasma pharmacokinetics of MTX were determined in groups of animals that had received a 300-mg/m2 loading dose of MTX followed by a 60-mg/m2/h infusion during an 18-hour period. One group received CPDG2 at the end of the infusion, and the other group served as a control. Two additional animals with high titers of anti-CPDG2 antibody also were studied. RESULTS During infusion, the steady-state MTX plasma concentration was 11.3 +/- 4.8 mumol/L. Without CPDG2, the postinfusion plasma MTX concentration remained above 0.1 mumol/L for more than 6 hours. After the administration of 50 U/kg of CPDG2, plasma MTX concentrations decreased to nontoxic levels (less than 0.05 mumol/L) within 30 minutes. The initial half-life (t1/2 alpha) of MTX decreased from 5.8 +/- 2.1 minutes to 0.7 +/- 0.02 minutes after enzyme administration. The postinfusion area under the plasma concentration time curve of MTX was 301 +/- 171 mumol/L/min without CPDG2 compared with 19.6 +/- 6.1 mumol/L/min with CPDG2. The immunogenicity studies performed indicated that although animals developed anti-CPDG2 antibodies, none of them manifested allergic symptoms. The effectiveness of CPDG2 was diminished but not eliminated in animals with high titers of anti-CPDG2 antibody. CONCLUSIONS CPDG2 is capable of rapidly decreasing plasma MTX concentrations to nontoxic levels. The administration of CPDG2 seems safe, well tolerated, and it may be useful as an alternative to LV rescue.
Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.
Authors: Pedersen-Bjergaard J , Sigsgaard T C , Nielsen D , Gjedde S B , Philip P , Hansen M , Larsen S O , Rørth M , Mouridsen H , Dombernowsky P 
Published: February 2017

PURPOSE To report five cases of acute monocytic or myelomonocytic leukemia after chemotherapy with 4-epidoxorubicin for breast cancer and to evaluate the risk of leukemia after the use of this drug. PATIENTS AND METHODS One hundred fifty-seven patients with advanced breast cancer were randomized to either 4-epi-doxorubicin plus cisplatin or 4-epi-doxorubicin alone. An additional 203 patients were treated prospectively with 4-epi-doxorubicin alone. All were observed closely for leukemic complications. RESULTS Three patients from the randomized study developed leukemia; all were in the subgroup of 74 patients who received 4-epi-doxorubicin plus cisplatin, whereas no leukemia was observed among the remaining 83 patients in the randomized study or among the additional 203 patients who were treated prospectively with 4-epi-doxorubicin alone (P = .023, log-rank test). In the subgroup of 74 patients who were treated with 4-epi-doxorubicin plus cisplatin, the cumulative risk of leukemia was 16.0% +/- 9.9% (mean +/- SE) 33 months after the start of therapy; the relative risk was 668 (95% confidence interval [Cl], 138 to 1,953). Two other cases of acute monocytic and myelomonocytic leukemia were observed after 4-epi-doxorubicin plus alkylating agents were administered for breast cancer. Three of five cases of leukemia presented balanced translocations to chromosome band 11q23 and two, loss of a whole chromosome no. 7 or its long arm. CONCLUSIONS 4-epi-doxorubicin is leukemogenic, and the leukemias are often acute monocytic or myelomonocytic with balanced chromosome translocations to band 11q23, such as in the leukemias after therapy with the epipodophyllotoxins. Furthermore, our results suggest a synergistic effect in leukemogenesis between 4-epi-doxorubicin targeting DNA-topoisomerase II and directly genotoxic drugs such as cisplatin or alkylating agents.
Dosing regimen of granulocyte-macrophage colony-stimulating factor to support dose-intensive chemotherapy.
Authors: Neidhart J A , Mangalik A , Stidley C A , Tebich S L , Sarmiento L E , Pfile J E , Oette D H , Oldham F B 
Published: February 2017

PURPOSE This trial evaluated the optimum dosing regimen for recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) to support a dose-intensive chemotherapy regimen given without progenitor cell replacement. PATIENTS AND METHODS Fifty-one patients with refractory malignancy received cyclophosphamide 2,500 mg/m2 on days 1 and 2, etoposide 500 mg/m2 on days 1, 2, and 3, and cisplatin 50 mg/m2 on days 1, 2, and 3. Patients were hospitalized from cycle days 1 to 4 for chemotherapy and readmitted for cytopenic temperatures above 38.5 degrees C. Cycles were repeated every 35 days in patients who responded to a total of three cycles. GM-CSF was given at doses of 250 to 1,000 micrograms/m2 by continuous intravenous infusion (CIV) or subcutaneously starting on cycle days 3 to 6. Two nonrandomized control groups are used. RESULTS The optimum regimen of GM-CSF for shortening the duration of leukopenia (WBC count less than 300/microL) was 500 micrograms/m2 given CIV. Duration of leukopenia was 5.9 days compared with 13.2 and 10.2 days in the controls (P less than .05). The optimum regimens for shortening duration of hospitalization, however, were 500 and 750 micrograms/m2/d given as divided (twice daily) subcutaneous injections. Durations of hospitalization were 9.6 and 9.8 days compared with 15.7 and 22.2 days in the controls (P less than .08). At the higher GM-CSF dose, only 36% of patients required readmission for cytopenic fever. Toxicities of GM-CSF at clinically useful doses were minimal. Twelve patients had complete response (24%) and 22 partial response (43%). CONCLUSIONS This dose-intensive regimen can be given safely without progenitor replacement. rhu GM-CSF decreases the duration of severe leukopenia and decreases the need for hospitalization and antibiotic therapy.
Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung.
Authors: Ziegler L D , Palazzolo P , Cunningham J , Janus M , Itoh K , Hayakawa K , Hellstrom I , Hellstrom K E , Nicaise C , Dennin R 
Published: February 2017

PURPOSE A phase I trial was undertaken to determine the toxicity and biologic effects of a combination of murine monoclonal antibody L6 (MoAb L6) plus subcutaneous (SC) interleukin-2 (IL-2). PATIENTS AND METHODS Fifteen patients with refractory adenocarcinoma (five breast, five lung, five colorectal), received L6 at 200 mg/m2 intravenously (IV) daily on days 1 to 7, followed by a 1-week rest period. IL-2 was given at either 2, 3, or 4.5 x 10(6) U/m2 daily doses times 4 days for a total duration of 3 weeks. RESULTS Side effects of L6 consisted of mild fever and chills along with a rash and serum sickness in one patient. One patient developed dyspnea and urticaria, that resolved with antihistamines. Maximum-tolerated dose (MTD) of SC IL-2 was 3 x 10(6) U/m2, with dose-limiting toxicities that consisted of grade 4 fatigue and dyspnea. Significant decreases in complement levels along with increases in absolute lymphocyte count and eosinophil count were observed. Mean antibody-dependent cellular cytotoxicity from mononuclear cells taken from patients who received IL-2 was elevated significantly compared with baseline in all patients independent of IL-2 dose (P less than .05). Serum IL-2 levels were elevated in 13 of 14 patients (range, 0.9 to 100 U/mL). Human antimouse antibody (HAMA) titers were elevated in nine of 14 (64%) patients who were tested between 3 and 8 weeks after L6 infusion. One patient with breast cancer had a transient mixed response, and one patient with colorectal cancer had a partial response. CONCLUSIONS L6 and SC IL-2 were well tolerated in the majority of patients when given in the outpatient setting. In view of the clinical efficacy of this combination, more phase II trials are warranted.
Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.
Authors: Markman M , Rowinsky E , Hakes T , Reichman B , Jones W , Lewis J L , Rubin S , Curtin J , Barakat R , Phillips M 
Published: February 2017

PURPOSE To evaluate the safety and pharmacology of the intraperitoneal (IP) administration of the antineoplastic agent taxol. PATIENTS AND METHODS Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were no intrapatient dose escalations. RESULTS The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. CONCLUSION Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.
Systemic chemotherapy of brain metastases from small-cell lung cancer: a review.
Authors: Kristensen C A , Kristjansen P E , Hansen H H 
Published: February 2017

PURPOSE For decades the treatment of choice in small-cell lung cancer (SCLC) with brain metastases has been corticosteroids and radiotherapy (RT) because of a presumed lack of penetrance of cytostatic agents into parenchymatous brain metastases. In recent years, several reports have appeared on radiologic and clinical responses to systemic chemotherapy without additional RT in patients with metastatic SCLC in the brain. We reviewed the literature and focused on the methodologic aspects in comparison with RT data. DESIGN We reviewed 12 patient series that included 116 patients and were published between 1981 and 1990. RESULTS The overall brain response to chemotherapy without irradiation in patients with intracranial metastases at diagnosis was 76%, whereas the response rate of brain relapses was 43%. CONCLUSIONS We conclude that intracranial metastases from SCLC seem to respond to chemotherapy as readily as other metastatic locations of SCLC do. Thus first-line cranial irradiation probably should be applied routinely only in cases of delayed brain metastases. Whether consolidating cranial RT should be given after a few courses of initial chemotherapy in SCLC patients with brain metastases at diagnosis is unclear and warrants a randomized evaluation.
Dose-related immunologic effects of levamisole in patients with cancer.
Authors: Janik J , Kopp W C , Smith J W , Longo D L , Alvord W G , Sharfman W H , Fenton R G , Sznol M , Steis R G , Creekmore S P 
Published: February 2017

PURPOSE This phase I study was conducted to determine the maximum-tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-gamma). PATIENTS AND METHODS Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN-gamma 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis. RESULTS The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-gamma. Dose-related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of > or = 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-gamma and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-gamma alone. CONCLUSION Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.
Body-composition changes in patients who gain weight while receiving megestrol acetate.
Authors: Loprinzi C L , Schaid D J , Dose A M , Burnham N L , Jensen M D 
Published: February 2017

PURPOSE Randomized placebo-controlled clinical trials have now established that megestrol acetate causes appetite stimulation and weight gain in patients with anorexia and/or cachexia. There is a paucity of available data to delineate the substance of this increased weight. PATIENTS AND METHODS Using dual-energy x-ray absorptiometry and tritiated body water methodologies, we performed body-composition measurements in 12 patients with advanced cancer before the institution of oral megestrol acetate (800 mg/d) and at subsequent 2-month intervals. RESULTS Seven of the 12 patients gained weight (2.1 to 16.5 kg) and had repeat body-composition measurements performed at the time of maximum weight gain. The vast majority of the gained weight was clearly from an increase in adipose tissue, while there was a suggestion that an increase in body fluid was responsible for a minority of the weight gain. CONCLUSION Megestrol acetate-induced weight gain is primarily the result of an increase in body mass.