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Vestnik Rossiiskoi Akademii... 2002To improve the action and selectivity of new drugs on tumor cells and the use of currently available pharmaceutical technologies to develop the systems of controlled... (Review)
Review
To improve the action and selectivity of new drugs on tumor cells and the use of currently available pharmaceutical technologies to develop the systems of controlled transport of well-known antitumor compounds is one of the ways of enhancing the efficiency of drug therapy for tumors. The tropicity of steroid hormones to definite organs and tissues makes it possible to use them as specific messengers of alkylating groups to target tissues and tumors. Hormone cytostatics synthesized by this principle have a double mechanism of hormonal and cytotoxic actions. The original Russian water-insoluble hormone cytostatistics testifenon, kortifen, and cytestrol acetate demonstrated local tissue irritation together with high antitumor activity. No rational dosage forms make it possible to conduct clinical trials by parenteral administration. The aim of this paper is to summarize the authors' results of designing hydrophobic antitumor hormone cytostatics. The advantages and disadvantages of different approaches to designing traditional dosage forms and to applying colloid liposomal systems for intravenous administration of water-insoluble agents are shown.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Corticosterone; Female; Humans; Injections, Intravenous; Liposomes; Nitrogen Mustard Compounds; Prednimustine
PubMed: 11882971
DOI: No ID Found -
Anticancer Research 2001The purpose of this study was to investigate the effect of long-term administration of G-CSF with regard to its impact on overall survival of patients with ovarian... (Clinical Trial)
Clinical Trial
The purpose of this study was to investigate the effect of long-term administration of G-CSF with regard to its impact on overall survival of patients with ovarian cancer. We report the results of a non-randomized trial on 64 patients with advanced ovarian cancer treated with 6 cycles of conventional chemotherapy. Chemotherapy comprised carboplatin 400 mg/m2 and epirubicin 70 mg/m2 on day 1 of each cycle and prednimustine 100 mg/m2 on days 3 to 7, every 28 days. Thirty-three patients received CEP chemotherapy with G-CSF support whereas 31 women received CEP chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day subcutanously on days 8 to 21 of each cycle. The severity of reduction in white cells and neutrophil count was significantly different in the two treatment groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users had a non significant 0.88-fold lower risk of dying from ovarian cancer (95% CI, 0.48-1.60, p=0.678). In a survival analysis using a Cox proportional hazards model, residual tumor remained as an independent prognostic factor. The increasing amount of residual tumor resulted in a 1.767-fold higher risk (95% CI, 1.23-2.53, p=0.002) of death secondary to the underlying disease. In conclusion, this trial has failed to demonstrate any negative impact on patients' overall survival for the additional use of G-CSF with platinum-based chemotherapy; our results were consistent with the beneficial effects of G-CSF treatment on cytotoxic chemotherapy-induced myelosuppression.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Drug Administration Schedule; Epirubicin; Female; Granulocyte Colony-Stimulating Factor; Humans; Middle Aged; Ovarian Neoplasms; Prednimustine; Survival Rate
PubMed: 11848547
DOI: No ID Found -
European Journal of Haematology Jan 2001Few studies have been performed regarding multiple myeloma (MM) in elderly patients. We report a retrospective series of 130 unselected patients with MM aged 75 yr or... (Review)
Review
Few studies have been performed regarding multiple myeloma (MM) in elderly patients. We report a retrospective series of 130 unselected patients with MM aged 75 yr or more at diagnosis. Presenting features were identical to those reported in younger patients, except for a higher rate of infection. Heavy comorbidity was characteristic of unselected geriatric patients. Ninety-four patients received conventional chemotherapy. The response rate was 62%. Treatment toxicity was mild. Median survival was 22 months. Durie-Salmon (DS) clinical stages II and III MM were severe and often led to death, while significantly more patients with DS stage I MM died from unrelated causes (p<0.0001). Univariate analysis showed that age > or = 85 yr, performance status > or = 2, creatinine level > or = 120 micromol/l, beta 2 microglobulin level > 4 mg/l, C-reactive protein level > 6 mg/l, platelet count < 100 x 10(9)/l, presence of infection and lack of response to chemotherapy were adverse prognostic factors for survival. In Cox multivariate regression analysis, age > or = 85 yr (p<0.0001), performance status > or = 2 (p<0.0001) and creatinine level > or = 120 micromol/l (p<0.0001) were independent factors in predicting short survival. This study provides evidence that in patients with symptomatic MM age should not be considered as a major obstacle to active treatment. Prospective clinical trials are needed in this population of patients and should include an assessment of quality of life.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cause of Death; Comorbidity; Cyclophosphamide; Dexamethasone; Doxorubicin; Etoposide; Female; France; Humans; Interferon-alpha; Life Tables; Lomustine; Male; Melphalan; Multiple Myeloma; Myeloma Proteins; Neoplasm Staging; Paraneoplastic Syndromes; Prednimustine; Prednisone; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Treatment Outcome; Vincristine
PubMed: 11168502
DOI: 10.1034/j.1600-0609.2001.00301.x -
Critical Reviews in Oncology/hematology Feb 2001We have evaluated the clinico-pathological and therepeutical outcome of patients aged 70 and older with malignant lymphomas treated at a single institute over a 20-year... (Review)
Review
We have evaluated the clinico-pathological and therepeutical outcome of patients aged 70 and older with malignant lymphomas treated at a single institute over a 20-year period of time. Among the several studies evaluated, the most important is a prospective randomized study comparing a new regimen, VMP (VP 16, Mitoxantrone and Prednimustine) vs the goal standard CHOP in unfavorable non-Hodgkin's lymphoma (NHL), showing that CHOP is significantly better than VMP in terms of objective response rate, progression free and overall survival. Therefore CHOP remains the standard regimen also for patients of over 70 years of age and stage II--IV intermediate and high grade NHL.
Topics: Aged; Aged, 80 and over; Humans; Lymphoma
PubMed: 11166589
DOI: 10.1016/s1040-8428(00)00103-7 -
Methods in Molecular Medicine 2001Human tumor cell lines have provided valuable model systems to study a wide variety of tumor characteristics including the cell biology, genetics, and chemosensitivity...
Human tumor cell lines have provided valuable model systems to study a wide variety of tumor characteristics including the cell biology, genetics, and chemosensitivity profiles of disease. A large number of ovarian cancer cell lines have now been established and are in widespread use Table 1) (1-15). Many of these have been selected to reflect specific situations, e.g., pre- and postchemotherapy models or different histo- logical subtypes. Table 1 Properties of Established Ovarian Carcinoma Cell Lines Prior Cell Line Histology Source Treatment Ref. PE01 P.D. Serous adenoca Ascites P/FU/CHL 1 PE04 P.D. Serous adenoca Ascites P/FU/CHL 1 PE06 P.D. Serous adenoca Ascites P/FU/CHL 2 PEA1 P.D. Adenoca Pleural None 2 PEA2 P.D. Adenoca Ascites P/Pred 2 PE016 P.D. Serous adenoca Ascites Radioth 2 PE014 W.D.Serous adenoca Ascites None 2 T014 W.D.Serous adenoca Sol. Met None 2 PE023 W.D.Serous adenoca Ascites P/CHL 2 SKOV-3 Adenoca Ascites T 3 SW626 Adenoca - - 3 OVCAR-2 Adenoca Ascites P/Cy 4 OVCAR-3 P.D. papillary adenoca Ascites P/Cy/Adr 5 OVCAR-4 Adenoca Ascites P/Cy/Adr 6 OVCAR-5 Adenoca Ascites None 7 OAW 28 Adenoca Ascites P / Mel 8 OAW 42 Serous adenoca Ascites P 8 41M Adenoca Ascites None 9 59M Endometr adenoca Ascites None 8 CH1 Papillary adenoca Ascites P/ JM8 8 138D Serous adenoca Ascites Carb 9 180D Adenoca Ascites P 9 200D Serous adenoca Solid None 9 253D Serous adenoca Ascites Cy/MPA 9 HOC-1 W.D. Serous adenoca Ascites None 10 HOC-7 W.D. Serous adenoca Ascites None 10 CAOV-3 Adenoca Tumour Cy/Adr/FU 10 COLO 110 Serous adenoca Sol. Met None 11 COLO 316 Serous adenoca Pleural None 11 COLO 319 Serous adenoca Ascites None 11 COLO 330 Serous adenoca Ascites Mel/Radiother 11 IGROV1 Adenoca Primary None 12 HTOA W.D. serous adenoca Primary None 13 OV-1063 Papillary adenoca Ascites Cy/Adr/P/HMM 14 DO-s W.D. mucinous adenoca Ascites - 15 P.D. = Poorly differentiated; W.D. = Well differentiated; adenoca = adenocarcinoma; pleural = pleural effusion; Sol.met. = solid metastasis; P = cisplatin; FU = 5-fluorouracil; CHL = chlorambucil; Pred = prednimustine; Radioth = radiotherapy; T = thiotepa; Cy = cyclophosphamide; Adr = adriamycin; Mel = melphalan; Carb = carboplatin; MPA = medroxyprogesterone actetate; HMM = examethylmelamine.
PubMed: 21340766
DOI: 10.1385/1-59259-071-3:155 -
Clinical Cancer Research : An Official... Sep 2000Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug...
Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug resistance protein (MRP1). To determine the clinical relevance of these multidrug resistance factors in previously untreated diffuse large B-cell lymphomas (n = 48), we studied LRP and MRP1 expression in lymphoma cells and their impact on clinical outcome. LRP and MRP1 expression were immunohistochemically assessed by means of the monoclonal antibodies LRP-56 and MRPr1, respectively. LRP was positive in 23% and MRP1 in 44% of the samples. LRP expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.01), and the International Prognostic Index (P = 0.0001). LRP-positive patients had a lower complete response rate to polychemotherapy than LRP-negative patients (18 versus 65%; P = 0.006). Patients with LRP expression had a shorter overall survival than those without LRP expression (median of 0.9 years versus median not reached; P = 0.001). MRP1 expression was independent of clinical and laboratory parameters and had no impact on the outcome of chemotherapy or survival of the patients. These data suggest that LRP expression but not MRP1 expression is an important mechanism of drug resistance associated with worse clinical outcome in previously untreated diffuse large B-cell lymphomas. Thus, the reversal of LRP-mediated drug resistance may improve clinical outcome in diffuse large B-cell lymphoma in the future.
Topics: ATP-Binding Cassette Transporters; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Resistance, Multiple; Etoposide; Female; Humans; Immunohistochemistry; Lomustine; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Prednimustine; Prednisone; Regression Analysis; Survival Analysis; Treatment Outcome; Vault Ribonucleoprotein Particles; Vincristine
PubMed: 10999723
DOI: No ID Found -
Critical Reviews in Oncology/hematology Aug 2000In elderly patients age-specific comorbidity often reduces the possibility of administering intensive chemotherapy and of obtaining response to treatment. Therefore,...
In elderly patients age-specific comorbidity often reduces the possibility of administering intensive chemotherapy and of obtaining response to treatment. Therefore, chemotherapy must differ from that for non-elderly patients, while maintaining the primary goal of a complete clinical response. We treated 19 patients over the age of 70 years (median age 75 years, range 70-86) with stage II-IV high-grade non-Hodgkin's lymphoma (NHL) with a combination regimen including idarubicin plus etoposide and prednimustine (or chlorambucil+prednisone), all administered orally on an outpatient basis. The therapeutic schedule included six 5-day courses of idarubicin 20 mg/sqm on day 1 (or 10 mg/sqm on days 1 and 3 in the nine patients last treated), etoposide 60 mg/sqm/12 h days 2-5, prednimustine 60 mg/sqm days 2-5, G-CSF 300 microg/day from day+7 until PMN>1000/microl. In ten patients prednimustine was replaced by chlorambucil 10 mg/sqm, days 2-5, and prednisone 50 mg days 2-5, because of non-availability of the drug. Of the 19 patients submitted to this regimen 15 (79%) obtained a clinical response: eight reached a complete response (CR), and seven a partial response (PR). Hematologic toxicity was generally mild. Only three patients had to be hospitalised for infection. Except alopecia, non-hematologic toxicities were negligible. At a median follow-up of 16 months, five of eight patients who obtained CR relapsed (median CR duration 7 months). The actuarial median survival is 34 months (range 6-46). This study demonstrates the feasibility and efficacy of an all-oral regimen including idarubicin, plus etoposide and prednimustine (or chlorambucil+prednisone) in NHL patients aged over 70 years.
Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Agranulocytosis; Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Evaluation; Etoposide; Female; Follow-Up Studies; Humans; Idarubicin; Lymphoma, Non-Hodgkin; Male; Prednimustine; Thrombocytopenia; Treatment Outcome
PubMed: 10936466
DOI: 10.1016/s1040-8428(00)00065-2 -
Gynecologic Oncology Feb 1999The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced ovarian cancer.
METHODS
Between 1985 and 1992 64 patients with radically operated ovarian cancers (4 stage IC, 2 stage II, 54 stage III, and 4 stage IV) were enrolled in a randomized study. Radical surgery comprised total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and pelvic and paraaortic lymphadenectomy. All patients received adjuvant chemotherapy with carboplatin IV 400 mg/m2, epirubicin IV 70 mg/m2 on day 1 and prednimustine orally 100 mg/m2 on days 3 to 7 at 1-month intervals. Thirty-two patients without residual disease were randomized to whole abdominal radiation (30 Gy, administered over 4 weeks). An additional 21.6 Gy were delivered to the pelvis and 12 Gy to the paraaortic region up to the diaphragm for total doses of 51.6 and 42 Gy, respectively. Cancer-related survival was calculated with the Kaplan-Meier and Cox proportional hazards methods.
RESULTS
The relapse-free and overall survival rates of patients who received adjuvant chemoradiotherapy were significantly higher than those of patients who received adjuvant chemotherapy only (68% vs 56% at 2 years and 49% vs 26% at 5 years, P = 0.013, and 87% vs 61% at 2 years and 59% vs 33% at 5 years, P = 0.029). The differences were most pronounced in patients with stage III disease (77% vs 54% at 2 years and 45% vs 19% at 5 years, P = 0. 0061, and 88% vs 58% at 2 years and 59% vs 26% at 5 years, P = 0. 012). Toxicities were acceptable.
CONCLUSION
Sequential combination of platinum-based chemotherapy with open-field abdominal radiotherapy is a promising adjuvant regimen for patients with advanced ovarian cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Disease-Free Survival; Epirubicin; Female; Follow-Up Studies; Humans; Middle Aged; Ovarian Neoplasms; Prednimustine; Radiotherapy, Adjuvant; Survival Rate
PubMed: 10021304
DOI: 10.1006/gyno.1998.5184 -
American Journal of Hematology Oct 1998Elderly patients with intermediate- or high-grade non-Hodgkin's lymphoma have a worse outcome than those who are younger than 60 years. It has been shown that aggressive... (Clinical Trial)
Clinical Trial
Elderly patients with intermediate- or high-grade non-Hodgkin's lymphoma have a worse outcome than those who are younger than 60 years. It has been shown that aggressive combination chemotherapy is poorly tolerated in older patients resulting in a subsequent decrease in dose intensity. A phase II trial was conducted with mitoxantrone, prednimustine, and vincristine (NSO) in this group of patients. NSO consists of mitoxantrone 12 mg/M2 intravenously on day one, vincristine 1.4 mg/M2 intravenously on day 1 (maximum dose of two mg), and prednimustine 100 mg/M2 orally once a day for four days. NSO was repeated every 21 days. Thirty-six patients were able to be evaluated. There were 18 males and 18 females with the median age of 71 (range 60-85). NSO was well tolerated and nonhematological toxicities were uncommon. More than 80% of the patients received 90% or greater of the intended dose. The complete response rate was 60.6% and partial response was 21.8%. At 60 months the Kaplan-Meier estimate of progression-free survival was 47.9% (standard error 8.6%) and actual survival was 40.6% (standard error 8.8%). There were no differences in outcome between those with performance status (PS) of zero or one and those with PS > 1. NSO is well tolerated by elderly patients including those with PS > 1. These results compare favorably with other combinations in elderly patients with aggressive non-Hodgkin's lymphoma.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoxantrone; Prednimustine; Remission Induction; Survival Rate; Treatment Outcome; Vincristine
PubMed: 9766801
DOI: 10.1002/(sici)1096-8652(199810)59:2<156::aid-ajh9>3.0.co;2-x -
Medicina Clinica May 1998
Review
Topics: Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Middle Aged; Mitoxantrone; Palliative Care; Prednimustine; Prednisolone; Prednisone; Prognosis; Vincristine
PubMed: 9650201
DOI: No ID Found