Abstract:
BACKGROUND:Compared with free drug, sterically stabilized liposomal drug has prolonged circulation time and, thereby, higher tumor selectivity and antitumor activity. The stability in plasma is an important consideration in the formulation of clinically useful liposomal drug. A Phase I study of a stable liposomal doxorubicin with polyethylene glycol (PEG) coating and phospholipid component of distearoyl phosphatidylcholine (DSPC) was performed to characterize its pharmacokinetic properties, toxicity profile, and maximal tolerated dose. METHODS:The starting dose was 30 mg/m(2) every 3 weeks with an increment of 10 mg/m(2) for each level. A cohort of at least three patients was entered for each level. Dose escalation stopped when more than one-third of patients had dose limiting toxicity (DLT), which was equal to or more than Grade 3 nonhematologic toxicity. Blood was sampled immediately before and at 5 minutes, 2 hours, 4 hours, 10 hours, 24 hours, 48 hours, 72 hours, and 168 hours after the completion of PEGylated liposomal doxorubicin (PLD) infusion. Plasma level of doxorubicin was determined with fluorometry, and the pharmacokinetic properties were analyzed. RESULTS:Twenty-six patients were entered, and 101 courses were studied. This DSPC PLD had a steady-state distribution volume (Vss) of 2.4 +/- 0.9 liters (mean +/- standard deviation), a clearance of 0.027 +/- 0.010 liters per hour, and a beta half-life of 65.0 +/- 17.8 per hour. These characteristics were dose independent, and the Vss and clearance were smaller than those of a well characterized PLD comprised of hydrogenated soybean phosphatidylcholine (HSPC). At the dose level of 50 mg/m(2), its plasma area under the concentration time curve was approximately twice that of HSPC PLD. Attenuation of acute toxicity, such as nausea, emesis, and alopecia, was noted in all dose levels. However, stomatitis was common from the dose level of 30 mg/m(2), and its incidence and severity increased with dosage and became dose limiting at 50 mg/m(2). A dose of 45 mg/m(2) every 3 weeks was then given in eight patients, and the side effects were acceptable. This dose was recommended for Phase II clinical trials. Fourteen of 17 patients with a dose level > or = 40 mg/m(2) were evaluable for response, but none achieved partial remission. CONCLUSIONS:This DSPC PLD had the characteristics of second-generation liposomal drug pharmacokinetically and toxicologically. The incidence of severe stomatitis was higher than that of HSPC PLD, corresponding to the difference in pharmacokinetics. Only limited antitumor activity was observed, although defining its therapeutic application will need further Phase II studies. Further prolongation of plasma stability of PLD may not be clinically beneficial considering the increased stomatitis and the reduced achievable dose intensity.
journal_name
Cancerjournal_title
Cancerauthors
Hong RL,Tseng YLsubject
Has Abstractpub_date
2001-05-01 00:00:00pages
1826-33issue
9eissn
0008-543Xissn
1097-0142pii
10.1002/1097-0142(20010501)91:9<1826::AID-CNCR1203journal_volume
91pub_type
临床试验,杂志文章相关文献
CANCER文献大全abstract:BACKGROUND:Hyalinizing clear cell carcinoma (HCCC) is an uncommon malignant salivary gland tumor that was characterized only recently as a distinct entity. Because of its histologic similarity to several other primary and metastatic tumors and its purported favorable clinical outcome after local resection, it is import...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/cncr.23974
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Human neoplasms often are accompanied by an inflammatory infiltrate. It has been proposed that this represents an immunologic response to the tumor. Dysgerminoma, a germ cell tumor of the ovary, is a classic example of this phenomenon. The authors investigated the immunophenotype of the tumor-infiltrating ly...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19930415)71:8<2562::aid-cncr2820
更新日期:1993-04-15 00:00:00
abstract:BACKGROUND:The aim of this work was to study the expression of alpha, beta1, and beta4 integrin subunits in meningiomas. METHODS:Seventeen atypical or anaplastic meningiomas were retrieved from the files of Hôpital de Bellevue, Saint-Etienne, France. They were compared with 17 benign meningiomas consecutively examined...
journal_title:Cancer
pub_type: 杂志文章
doi:
更新日期:1999-12-15 00:00:00
abstract::Although weight loss has an adverse impact on cancer patient survival, the ability of caloric provision via total parenteral nutrition (TPN) to favorably influence outcome in chemotherapy-treated populations is not established. In randomized trials, no significant improvement in either response or survival was associa...
journal_title:Cancer
pub_type: 临床试验,杂志文章,评审
doi:10.1002/1097-0142(19850101)55:1+<268::aid-cncr2820
更新日期:1985-01-01 00:00:00
abstract::Elective irradiation of sites of potential occult tumor spread is often part of a patient's radiation therapy program. The required radiation dose (D) depends on the probability that occult disease exists (P(occ)), the number of sites at risk (A), the number of tumor clonogens present (Ni), their radiation sensitivity...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19901215)66:12<2498::aid-cncr282
更新日期:1990-12-15 00:00:00
abstract:BACKGROUND:The demonstration of the monoclonality of immunoglobulin heavy chain (IgH) gene rearrangement is an indispensable method for the diagnosis of B-cell lymphoma as well as histocytochemical analysis. For the detection of IgH gene rearrangement, the extraction of DNA from a homogenous cell population is necessar...
journal_title:Cancer
pub_type: 临床试验,杂志文章
doi:10.1002/cncr.11331
更新日期:2003-08-25 00:00:00
abstract:BACKGROUND:Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of sur...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.31186
更新日期:2018-04-15 00:00:00
abstract:BACKGROUND:Methotrexate is a chemotherapeutic agent frequently utilized for the treatment of malignant, rheumatic, and pulmonary diseases. Although this agent has been extensively used for more than 45 years, there are few reports of immediate systemic hypersensitivity reactions. The reported immediate reactions includ...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/(SICI)1097-0142(19960515)77:10<2123::AID-C
更新日期:1996-05-15 00:00:00
abstract:BACKGROUND:Radiotherapy (RT) after breast-conserving surgery (BCS) has produced significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was shown previously that a delay in the initiation of RT resulted in a higher local recurrence (LR) rate. In the current retrospective analysis, the authors investi...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.21161
更新日期:2005-07-15 00:00:00
abstract:BACKGROUND:Ovarian tumors of borderline malignancy have a less aggressive behavior and tend to occur at a younger age than their invasive counterparts. The role and extent of fertility-sparing conservative treatments is under continuous evaluation. METHODS:The current study was a retrospective review of 82 patients wi...
journal_title:Cancer
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Flow cytometric measurements were done on 51 ovarian carcinoma specimens collected from consecutive patients in a prospective study. The ploidy status was related to the course of the disease. The tumors from 26 (52%) of 50 evaluable patients had DNA aneuploidy. Patients with diploid tumors were more often considered ...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19880301)61:5<971::aid-cncr28206
更新日期:1988-03-01 00:00:00
abstract::The records of 1,497 patients with histologically proven adenocarcinoma of the stomach were reviewed from Charity Hospital over the 25-year period, 1948 to 1973. The operability rate was 82% and the resectability rate was 48%. In this series gastric carcinoma predominated in males and Negroes. Necropsy studies indicat...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197803)41:3<941::aid-cncr2820410
更新日期:1978-03-01 00:00:00
abstract::In a 3 1/2 year cytogenetic study of 107 leukemia patients diagnosed in childhood and adloescence, 8 presented with chronic myelogenous leukemia (CML). Seven of the 8 had chromosomal abnormalities. Six had the Ph1 chromosome; 5 had the usual 9;22 translocation. Two patients had involvement with chromosome 15; one had ...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197907)44:1<210::aid-cncr2820440
更新日期:1979-07-01 00:00:00
abstract:BACKGROUND:To clarify the differences in angiogenesis between benign and malignant ovarian tumors, the authors examined the immunohistochemical characteristics and the density of tumor vessels in both tumor groups. Intratumoral vascularization was observed preoperatively by transvaginal color Doppler ultrasound. METHO...
journal_title:Cancer
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::A total of 1026 patients with gastric cancer was followed up for five years after surgery and classified into different groups according to surgeons' assessment of nodal involvement, serosal invasion, peritoneal spread, and hepatic metastasis. The survival of each group was studied by parametric analysis, using the lo...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19801215)46:12<2709::aid-cncr282
更新日期:1980-12-15 00:00:00
abstract:BACKGROUND:Greater than one-half of children who are treated for acute lymphoblastic leukemia (ALL) develop ≥1 treatment-related medical conditions in their lifetime, many of which are known risk factors for diabetes mellitus. In the current study, the authors evaluated the prevalence and risk factors of diabetes melli...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.32596
更新日期:2020-02-15 00:00:00
abstract::Flow cytometry was used to compare binding of wheat germ agglutinin (WGA) and Lens culinaris lectin (Lcl) to peripheral lymphocytes (PBL) from normal subjects and 26 patients with chronic lymphocytic leukemia (CLL). As defined by the interactions of WGA and Lcl with cell surface receptors, normal unfractionated PBL an...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19830601)51:11<2083::aid-cncr282
更新日期:1983-06-01 00:00:00
abstract::Melanoma cell oncolysate, prepared with Newcastle disease virus, was administered as an immunostimulant to 13 patients with metastatic melanoma. The oncolysate was well tolerated. Six treated patients evidenced a decrease in the size of skin nodules or diseased lymph nodes. Visceral lesions were not favorably influenc...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197708)40:2<680::aid-cncr2820400
更新日期:1977-08-01 00:00:00
abstract::Between June 1977 and December 1978, occult testicular leukemia (OTL) was discovered at three years of continual complete remission (CCR) from the time of diagnosis of acute lymphoblastic leukemia (ALL) in 5 of 59 (8.5%) of males undergoing bilateral wedge testicular biopsy at 1 of 15 participating Southwest Oncology ...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19810201)47:3<470::aid-cncr28204
更新日期:1981-02-01 00:00:00
abstract::High tissue concentrations of human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) were revealed by radioimmunoassay in a hepatic tumor which was surgically removed from a two-year, eight-month-old boy manifesting sexual precocity. Histologically the tumor showed an embryonal type hepatoblastoma admixed with...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19830501)51:9<1647::aid-cncr2820
更新日期:1983-05-01 00:00:00
abstract::This report describes 11 adults with non-Hodgkin's lymphoma who presented with symptoms caused by large mediastinal masses. Patients with lymphoblastic lymphoma were excluded from this analysis. Most of the patients were young women with localized disease at presentation. Ten tumors were diffuse large cell ("histiocyt...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19820715)50:2<277::aid-cncr28205
更新日期:1982-07-15 00:00:00
abstract::A 17 year old man with a primary intracranial germ cell tumor in the pituitary region is reported. Both serum alpha-fetoprotein (AFP) and serum human chorionic gonadotropin (hCG) were found elevated preoperatively. Normal levels of serum AFP and hCG were found after operation and radiotherapy. By indirect immunofluore...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197806)41:6<2315::aid-cncr282041
更新日期:1978-06-01 00:00:00
abstract:BACKGROUND:The Hanford Tribal Service Program offers technical assistance and health education to American Indian tribes in an area reported to be affected by radiation from the Hanford Nuclear Reservation, which was developed and operated by the United States federal government. This article describes strategies used ...
journal_title:Cancer
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract:BACKGROUND:Cyclin D1 expression has been reported in a subset of patients with diffuse large B-cell leukemia (DLBCL), but studies have been few and generally small, and they have demonstrated no obvious clinical implications attributable to cyclin D1 expression. METHODS:The authors reviewed 1435 patients who were diag...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.28664
更新日期:2014-06-15 00:00:00
abstract::A new Hodgkin's cell line, designated HD-70, was established from the peripheral blood of a 69-year-old man with Hodgkin's disease of nodular sclerosing type. The cell line grows in a single cell suspension and has a doubling time of 28 hours. The cells have a round or irregular nucleus or multiple nuclei in relativel...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19920215)69:4<1034::aid-cncr2820
更新日期:1992-02-15 00:00:00
abstract:BACKGROUND:We investigated p16(INK4A) expression in branchial cleft cysts and its utility in distinguishing branchial cleft cysts from metastatic head and neck squamous cell carcinomas (SCCs) in fine-needle aspiration biopsies (FNABs). METHODS:A study set comprising 41 resections (15 SCC and 26 branchial cleft cysts) ...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncy.20001
更新日期:2009-04-25 00:00:00
abstract::The effect of multimodal immunotherapy was studied in rats bearing primary gastrointestinal tumors induced by 1,2-dimethylhydrazine dihydrochloride. Multimodal immune manipulation consisted of combinations of splenectomy, C. parvum, unblocking serum, unblocked lymphoid cells, and levamisole. Such immunologic intervent...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/1097-0142(197811)42:5<2079::aid-cncr282042
更新日期:1978-11-01 00:00:00
abstract:BACKGROUND:Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). ...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.26409
更新日期:2012-03-15 00:00:00
abstract:BACKGROUND:The identification of brain metastases in patients with malignant disease has important implications for determining their treatment and prognosis. Asymptomatic metastatic brain tumors may be detected by surveillance imaging techniques, but longitudinal follow-up of patients who are at risk is sporadic prima...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.21220
更新日期:2005-08-15 00:00:00
abstract:BACKGROUND:A phase 1 trial was used to evaluate a combination of cisplatin, gemcitabine, and escalating doses of veliparib in patients with untreated advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2-mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to determine t...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.31218
更新日期:2018-04-01 00:00:00