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1.
Ann Oncol ; 29(3): 737-743, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29267856

ABSTRACT

Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.


Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma, Ovarian Epithelial/drug therapy , Maintenance Chemotherapy/adverse effects , Ovarian Neoplasms/drug therapy , Pyrimidines/adverse effects , Quality of Life , Sulfonamides/adverse effects , Adult , Angiogenesis Inhibitors/adverse effects , Double-Blind Method , Female , Humans , Indazoles , Maintenance Chemotherapy/methods , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Patient Reported Outcome Measures , Progression-Free Survival , Time-to-Treatment
2.
Ann Oncol ; 27(12): 2236-2241, 2016 12.
Article in English | MEDLINE | ID: mdl-27789470

ABSTRACT

BACKGROUND: Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC). PATIENTS AND METHODS: Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points. RESULTS: A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4-10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4-27.6 resp. 26.0-36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P < 0.001), with 17.4% leucopenia, 27.8% neutropenia and 15.9% thrombopenia. CONCLUSION: The combination of carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Topotecan/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Austria , Carboplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/analogs & derivatives , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Quality of Life , Topotecan/adverse effects , Gemcitabine
3.
Anaesthesist ; 62(4): 293-5, 2013 Apr.
Article in German | MEDLINE | ID: mdl-23494023

ABSTRACT

A 29-year-old primagravida developed severe chest pains during labor. An emergency caesarean section was performed as the symptoms persisted. Imaging diagnosis immediately after delivery revealed an acute proximal (type A) aortic dissection. The patient was transferred to the nearest cardiothoracic surgery centre and successful emergency surgical aortic repair was performed. The perioperative course of a type A aortic dissection during pregnancy and labor is complicated by time pressure, diagnostic restrictions until delivery and potentially fatal uterine bleeding during cardiopulmonary bypass and hypothermic cardiac arrest. This case report describes the diagnosis and the surgical, anesthesiological and gynecological management of this life-threatening peripartum complication.


Subject(s)
Aortic Aneurysm/surgery , Aortic Dissection/surgery , Pregnancy Complications, Cardiovascular/surgery , Adult , Anesthesia , Aortic Dissection/diagnostic imaging , Aortic Aneurysm/diagnostic imaging , Cesarean Section , Echocardiography , Echocardiography, Transesophageal , Electrocardiography , Emergency Medical Services , Female , Humans , Peripartum Period , Pregnancy , Pregnancy Complications, Cardiovascular/diagnostic imaging , Tomography, X-Ray Computed
4.
Br J Cancer ; 105(3): 360-5, 2011 Jul 26.
Article in English | MEDLINE | ID: mdl-21750553

ABSTRACT

BACKGROUND: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin-paclitaxel (CP) or carboplatin-liposomal doxorubicin (CPLD). METHODS: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 10(9) per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. RESULTS: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008).Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). CONCLUSION: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Doxorubicin/administration & dosage , Leukopenia/chemically induced , Ovarian Neoplasms/drug therapy , Paclitaxel/adverse effects , Adult , Aged , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Male , Peripheral Nervous System Diseases/chemically induced , Prognosis , Recurrence
5.
Ann Oncol ; 22(11): 2417-2423, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21402619

ABSTRACT

BACKGROUND: CALYPSO (CAeLYx in Platinum Sensitive Ovarian) patients compared carboplatin-pegylated liposomal doxorubicin (C-PLD) with carboplatin-paclitaxel (C-P) in patients with late-relapsing recurrent ovarian cancer (ROC). We analyzed outcomes in patients ≥70 years. PATIENTS AND METHODS: Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing >6 months after first- or second-line platinum-based therapy were randomly assigned to 4-weekly C area under the curve (AUC) 5 plus PLD 30 mg/m(2) or 3-weekly C AUC 5 plus P 175 mg/m(2) for six or more cycles. RESULTS: One hundred and fifty-seven (16%) patients ≥70 years (median: 74 years, C-PLD; 73 years, C-P; range 70-82 years) were included (n = 71, C-PLD; n = 86, C-P). In comparing elderly and younger, elderly patients experienced fewer grade ≥2 allergic reactions (P = 0.005) but more grade ≥2 sensory neuropathy (P = 0.007). Myelosuppression did not differ with age. Elderly patients completed planned treatment as frequently as younger (79%, C-PLD; 82%, C-P). In comparing arms within elderly patients, C-P was associated with more grade ≥2 alopecia, sensory neuropathy, arthralgia/myalgia (P < 0.001 for all), severe leukopenia plus febrile neutropenia; C-PLD was associated with more grade ≥2 hand-foot syndrome (P = 0.005). Median progression-free survival was 11.6 months (C-PLD) and 10.3 months (C-P; P = 0.44). CONCLUSIONS: Patients ≥70 years experienced more neuropathy, with a higher incidence in the C-P arm. Similar to all study patients, C-PLD provided a better therapeutic index with less toxicity than C-P in elderly women with platinum-sensitive ROC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Age Factors , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/analogs & derivatives , Female , Humans , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Quality of Life , Treatment Outcome
6.
Eur J Gynaecol Oncol ; 30(5): 497-9, 2009.
Article in English | MEDLINE | ID: mdl-19899399

ABSTRACT

OBJECTIVE: There are few data in the literature as to whether findings at routine preoperative gynecologic examination of patients with primary endometrial cancer including cervical cytology, colposcopy and rectovaginal bimanual pelvic exam could predict cervical extension of the disease. METHODS AND MATERIALS: The present retrospective study was undertaken to preoperatively identify potential clinical parameters associated with the histological diagnosis of cervical involvement by primary endometrial cancer in the hysterectomy specimen. We reviewed the records of 104 patients with Stage II endometrial cancer treated at our institution between 1985 and 2005 by simple or radical abdominal hysterectomy with special emphasis on cervical Pap smear, colposcopy, cervical palpation as well as rectal parametrial assessment. Patients with Stage I disease operated on before and after each study patient were selected as controls (n = 208). Patients with more advanced disease were excluded. RESULTS: Overall, 312 records of patients with primary endometrial cancer were reviewed. Patients with Stage II disease had a significantly lower prevalence (p < 0.0001) of endometrioid carcinomas and a significantly higher (p < 0.01) prevalence of G3 tumors compared to the control patients. Pap smears and colposcopic findings were abnormal in 39% of patients with Stage II and in 9% and 10% of patients with Stage I disease (p < 0.0001). Of patients with Stage II disease, 42% had a suspicious cervical palpation compared to only 4% of patients with Stage I disease (p < 0.0005). Parametrial assessment was suspicious in 16% of patients with Stage II disease and in no patient with Stage I disease (p < 0.001). CONCLUSION: The four routine clinical parameters Pap smear, colposcopy, cervical palpation and rectal parametrial examination are significantly more often pathologic in patients with Stage II than in Stage I disease. The majority of patients with Stage II disease had at least one of these tests positive. Thus they may be useful to preoperatively detect cervical involvement by primary endometrial cancer.


Subject(s)
Endometrial Neoplasms/pathology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Colposcopy , Female , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Papanicolaou Test , Physical Examination , Retrospective Studies , Vaginal Smears
7.
J Cancer Res Clin Oncol ; 134(10): 1113-21, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18392852

ABSTRACT

PURPOSE: BRCA1 mutation carriers are at high risk for breast cancer (BC). The risk management strategy may include radiological investigations for early detection or prophylactic mastectomy (PM). For a mutation carrier, PM may be more significant than surveillance alone when pre-malignant and malignant changes occur increasingly in mastectomy specimens, given normal findings on radiological investigations. In the present study we retrospectively investigated the differences between histological findings in PM specimens of BRCA1 carriers and those of a control group. METHODS: Twenty-four healthy and 28 affected carriers in the presence of normal preoperative radiological findings were included in the study. To compare the frequency of pre-malignant and malignant lesions in PM specimens, a control group matched for age and disease status was included. T-tests for independent samples and Wilcoxon's signed-rank test were used for comparison of groups. RESULTS: The entire study group differed significantly from the control group (42.3 vs. 5.8%; P < 0.001) in terms of the occurrence of pre-malignant and malignant lesions. Both, the sub-group comparison of healthy mutation carriers as well as diseased carriers with their controls, showed a significant difference in terms of the occurrence of pre-malignant and malignant changes (45.8 vs. 0%; P = 0.002; 39.3 vs. 10.7%; P = 0.03). In PM specimens of mutation carriers, carcinomas were identified in 5.8% (3/52) and pre-malignant changes in 36.5% (19/52). CONCLUSIONS: BRCA1 mutation carriers should be informed of the fact that pre-malignant and even malignant changes are frequently found in PM specimens despite normal radiological findings.


Subject(s)
Breast Neoplasms/epidemiology , Genes, BRCA1 , Mastectomy , Precancerous Conditions/epidemiology , Adult , Breast Neoplasms/genetics , Breast Neoplasms/prevention & control , Female , Genetic Predisposition to Disease , Heterozygote , Humans , Mutation , Precancerous Conditions/genetics , Precancerous Conditions/prevention & control , Prevalence
8.
Anticancer Res ; 26(2B): 1627-30, 2006.
Article in English | MEDLINE | ID: mdl-16619583

ABSTRACT

BACKGROUND: Primary metastatic breast cancer with bone marrow involvement and pronounced thrombocytopenia is rare. The myelosuppressive effect of most cytotoxic drugs limits chemotherapy in patients with cytopenia due to marrow involvement. CASE REPORT: A 62-year-old patient, who presented with locally and systemically advanced breast cancer, is reported. The initial work-up revealed bone marrow carcinosis with thrombocytopenia of less than 20,000/mm3 lung and osseous metastases without signs of suppressed erythropoiesis and leucopoiesis. The patient was stabilized with 6 different standard-dose chemotherapy regimens, antihormonal therapy, and trastuzumab before dying 57 months after first diagnosis. The patient received only platelet transfusions on 2 instances with platelets of 2,000/mm3. CONCLUSION: This case illustrates that aggressive standard chemotherapy may be feasible in selected patients with bone marrow carcinosis-associated thrombocytopenia without major bleeding episodes.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Thrombocytopenia/complications , Bone Marrow/pathology , Breast Neoplasms/blood , Female , Humans , Middle Aged , Thrombocytopenia/pathology
9.
Cancer Lett ; 44(3): 221-6, 1989 Mar.
Article in English | MEDLINE | ID: mdl-2924289

ABSTRACT

The aim of the present study was to investigate to what extent the induction of leukemia by the carcinogenic agent cyclophosphamide (CPA) might be influenced by the genetic predisposition. CPA was s.c. administered at 26 mg/kg and 13 mg/kg weekly for lifetime to AKR mice which are genetically predisposed to develop leukemias, and to NMRI mice, that exhibit a low spontaneous leukemia rate. CPA dose-dependently increased the median life span in AKR mice by 27% and 76% (P less than 0.001), and decreased the incidence in leukemias by 17% and 37% (P less than 0.01), respectively. In NMRI mice, CPA significantly increased the incidence of leukemias by 46% at the low dose (P less than 0.02) and 26% at the high dose (P less than 0.03), respectively. The apparently parallel observations of the lower leukemia incidences following the higher CPA-dosage in both strains probably are related to different mechanisms of action: in the susceptible, genetically determined AKR mice the therapeutic effect of CPA prevailed its carcinogenic potential and the genetic host factors whereas in the resistant NMRI mice the cytotoxic efficacy of CPA reduced its carcinogenicity at the higher dosage.


Subject(s)
Cyclophosphamide/toxicity , Leukemia, Experimental/chemically induced , Animals , Dose-Response Relationship, Drug , Female , Mice , Mice, Inbred AKR , Species Specificity
10.
Cancer Lett ; 31(3): 311-8, 1986 Jun.
Article in English | MEDLINE | ID: mdl-3719571

ABSTRACT

The administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide FANFT) by gavage to female NMRI-mice resulted in a high incidence of neoplasms of the forestomach. From 117 effective animals which were pooled from 3 dosed groups, 30 squamous cell carcinomas and 26/117 papillomas of the forestomach were diagnosed. Only 5/117 neoplasms of the urinary bladder occurred. The average cumulative dose administered was 1180 mg/mouse, and the mean latent period for the induction of forestomach tumours was 574 days. The mode of application seems to be an important factor in the carcinogenicity of FANFT.


Subject(s)
Adenocarcinoma/chemically induced , Carcinoma, Squamous Cell/chemically induced , FANFT/toxicity , Papilloma/chemically induced , Stomach Neoplasms/chemically induced , Thiazoles/toxicity , Urinary Bladder Neoplasms/chemically induced , Administration, Oral , Animals , FANFT/administration & dosage , Female , Mice , Mice, Inbred Strains
11.
J Cancer Res Clin Oncol ; 114(2): 183-5, 1988.
Article in English | MEDLINE | ID: mdl-3350851

ABSTRACT

The results of clinical studies dealing with first and second line chemotherapy of metastatic breast cancer published between 1975 and early 1986 which involved 9350 women were reviewed. Our special aim was to evaluate combination chemotherapy and its influence on overall survival in late stage breast cancer patients. No significant improvement in overall survival times was found in this selected group of patients who were treated with intense palliative chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Female , Humans , Neoplasm Metastasis
12.
J Cancer Res Clin Oncol ; 113(5): 437-45, 1987.
Article in English | MEDLINE | ID: mdl-3624299

ABSTRACT

Four experiments investigating the antitumor activity of bacterial lipopolysaccharide (LPS) against the autochthonous methylnitrosourea-induced mammary carcinoma are summarized. Administration of LPS alone i.v. caused distinct regression of small tumors following its first injection. This therapeutic effect, however, was short-lived and could not be maintained by administering a second dose. The observed antineoplastic activity of LPS was dose-related, whereas no dose-response relationship was observed with respect to its toxicity. A series of experiments in which LPS was combined with other compounds to possibly exploit its activity while reducing the toxicity were performed. Neither the combination with cytotoxic drugs such as 4'-(9-acridinylamino)-methansulfone-m-aniside or cyclophosphamide nor that with 1-octadecyl-2-methoxy-rac-glycero-3-phosphocholine or hexadecylphosphocholine showed sufficient anticancer activity at acceptable toxicity. In all experiments promising efficacy was observed at high dosages but also high toxicity. When the dosages were reduced, diminished antineoplastic activity was found together with overproportionally high mortality. It might therefore be concluded that the active dose range of LPS cannot be reached clinically because of its inherent toxicity.


Subject(s)
Lipopolysaccharides/therapeutic use , Mammary Neoplasms, Experimental/therapy , Animals , Antineoplastic Agents/administration & dosage , Combined Modality Therapy , Dose-Response Relationship, Immunologic , Female , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/adverse effects , Mammary Neoplasms, Experimental/chemically induced , Methylnitrosourea , Rats , Rats, Inbred Strains
13.
J Cancer Res Clin Oncol ; 116(5): 431-3, 1990.
Article in English | MEDLINE | ID: mdl-2229131

ABSTRACT

The ability of two supposed DNA-repair inhibitors to modulate cisplatin-induced cytotoxicity in a human ovarian cancer cell line (CAOV-3) and a human cervical cancer cell line (Me-180) was investigated using a short-term chemosensitivity assay based on bioluminescence of cellular adenosine triphosphate (ATP). Cisplatin concentrations bracketing the reported peak plasma concentration (2.5 micrograms/ml) were used and the 50% inhibitory concentrations were determined by linear regression of log-transformed survival data. At 2.5 mM, the methylxanthine caffeine enhanced cisplatin sensitivity 2.9-fold in CAOV-3 cells and 2.7-fold in Me-180 cells. At 2.5 mM, pentoxifylline, a closely related methylxanthine, increased cisplatin sensitivity 2.9-fold in CAOV-3 cells and 3.4-fold in Me-180 cells. Chemical modification of cisplatin-induced cytotoxicity by assumed inhibition of DNA-repair mechanisms may hold promise for clinical application in the treatment of gynecological cancer.


Subject(s)
Cisplatin/therapeutic use , Ovarian Neoplasms/drug therapy , Xanthines/pharmacology , Adenosine Triphosphate/biosynthesis , Caffeine/pharmacology , Cell Survival/physiology , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques
14.
J Cancer Res Clin Oncol ; 114(3): 317-20, 1988.
Article in English | MEDLINE | ID: mdl-3384846

ABSTRACT

The anticancer activity of estradiol-linked 2-chloroethylnitrosoureas in methylnitrosourea-induced rat mammary carcinoma was investigated using the short-term assay and the bilayer soft agar system after in vitro exposure as well as the monolayer methylcellulose assay following in vivo treatment. The aim was to evaluate to what extent previous in vivo findings are paralleled by the results of two in vitro test systems and the monolayer culture technique ex vivo. From the test systems investigated and under the conditions used, the results of the short-term test and the monolayer methylcellulose assay did not show a correlation with previous in vivo findings. Only the results of the bilayer clonogenic assay paralleled therapeutic parameters in vivo, although the degree of activity obtained in vivo was not reflected in vitro.


Subject(s)
Antineoplastic Agents , Colony-Forming Units Assay , Estradiol/analogs & derivatives , Mammary Neoplasms, Experimental/drug therapy , Nitrogen Mustard Compounds/therapeutic use , Tumor Stem Cell Assay , Animals , Estradiol/therapeutic use , Female , Mammary Neoplasms, Experimental/chemically induced , Methylnitrosourea , Rats , Statistics as Topic
15.
J Cancer Res Clin Oncol ; 121(4): 203-10, 1995.
Article in English | MEDLINE | ID: mdl-7751318

ABSTRACT

The human colon carcinoma cell line SW 707 was exposed for up to 72 h to the new antineoplastic agent 4-amino-N-(2'-aminophenyl)benzamide (GOE 1734, dinaline). Thereafter, uptake measurements with fluorodeoxy-[14C]glucose (FdGlc) were performed and cell-cycle fractions as well as adenine nucleotide pools were determined by flow cytometry and HPLC. One day after a 24 h exposure to 20-540 microM dinaline a 2.0-to 2.5-fold enhancement of FdGlc uptake was observed, and the values after 48-h or 72-h incubations showed a 2.5- to 3.5-fold or a 2.0-fold increase respectively. For all periods of exposure a diminished S phase (3%-71% of control) was found initially after incubation, demonstrating the antiproliferative effect of dinaline, with total recovery after 1 day. Adenine nucleotide pools were not diminished concomitantly. The enhanced FdGlc uptake caused by dinaline was the basis for choosing 2-deoxyglucose (dGlc) as the combination partner, which acts as an antimetabolite to enzymes involved in glucose metabolism. Several combinations of dinaline and dGlc were analyzed for their effects on growth inhibition. Almost 50% additional decrease in cell number as compared to monotherapy with dinaline was found after coexposure to 12 mM dGlc and 20 microM dinaline 24 h after incubation. Similar effects were observed 2 days after incubation with the two drugs. After 3 days, the cell numbers reached monotherapy levels. Since the cytostatic effect of dinaline could be enhanced by dGlc although incubation with dGlc alone caused no changes in cell number, the combined effect of both agents is synergistic. These results imply that dinaline might have applications in combination treatment in vivo.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Phenylenediamines/pharmacology , Adenine Nucleotides/metabolism , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Carbon Radioisotopes , Cell Line , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Deoxyglucose/administration & dosage , Deoxyglucose/analogs & derivatives , Deoxyglucose/pharmacokinetics , Deoxyglucose/pharmacology , Flow Cytometry , Fluorodeoxyglucose F18 , Glucose/pharmacokinetics , Humans , Phenylenediamines/administration & dosage , Tumor Cells, Cultured/drug effects
16.
J Cancer Res Clin Oncol ; 113(1): 27-30, 1987.
Article in English | MEDLINE | ID: mdl-3818776

ABSTRACT

This methodological study describes three surgical procedures for locoregional and systemic drug administration, which are based on a similar experimental design. Cannulation of the arterial and portal access to the liver in comparison to the general venous system, and arterial access to the large intestine through a permanently implantable system, suitable for serial bolus injections and infusions in unrestrained rats, is presented (experiment I). Furthermore, an infusion system for longterm administration (experiment II) and a method for blood sampling during locoregional or systemic infusion procedures (experiment III) have been developed. The positioning and free flow of the catheters were checked by means of scintigraphy, administration of fluorescein under UV light and angiography in animals of experimental series I. After 7 days, no obstruction was detected. On day 15 and 30 following implantation 73.3% and 58.3% of the animals, respectively, showed unimpeded flow through the catheter system. The methods described here were well tolerated by the animals without alteration of their general condition and are currently in use in a series of chemotherapeutic and pharmacokinetic investigations.


Subject(s)
Blood Specimen Collection/veterinary , Pharmaceutical Preparations/administration & dosage , Animals , Blood Specimen Collection/methods , Catheterization , Female , Male , Pharmaceutical Preparations/blood , Rats , Rats, Inbred Strains , Time Factors
17.
Obstet Gynecol ; 86(2): 259-64, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7617357

ABSTRACT

OBJECTIVE: To evaluate the prognostic importance of preoperative CA 125 levels in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer in comparison with the established prognostic factors: degree of differentiation, FIGO substage, and age. METHODS: In a retrospective analysis, the traditional prognostic factors and CA125 levels (cutoff value 65 U/mL) were studied in 201 patients who were treated in five centers during 1984-1993. Patients with borderline tumors or non-epithelial ovarian carcinomas were excluded, as were women in whom CA 125 had not been determined preoperatively. RESULTS: In univariate analysis (Mantel test), overall survival decreased significantly in patients positive for CA 125 (P < .001). Substage (P = .004) and histologic grade (P = .01) also significantly influenced survival prognosis. When the effects of preoperative CA 125 levels were correlated with histologic grade, all three subgroups with CA 125 levels equal to or greater than 65 U/mL were associated with a decreased survival probability (grade 1, P = .04; grade 2, P = .003; grade 3, P = .01). Multivariate analysis (Cox model) identified preoperative CA 125 as the most powerful prognostic factor for survival (P < .001), the risk of dying of disease being 6.37 times higher (95% confidence interval 2.39-16.97) in CA 125-positive patients. Although FIGO substage retained its significant influence on survival (P = .03), histologic grade and age were not prognostically important. CONCLUSION: Randomized trials investigating the efficacy of adjuvant treatment in patients with FIGO stage I epithelial ovarian cancer should also include stratification by preoperative CA 125 levels.


Subject(s)
Biomarkers, Tumor/blood , CA-125 Antigen/blood , Ovarian Neoplasms/mortality , Age Factors , Female , Humans , Life Tables , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/blood , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Analysis
18.
Oncol Rep ; 7(3): 639-44, 2000.
Article in English | MEDLINE | ID: mdl-10767382

ABSTRACT

Tumor anemia is common in patients with malignant tumors and it was repeatedly demonstrated to be associated with impaired prognosis in patients with malignant tumors. We conducted a retrospective analysis based on 553 patients with histologically proven epithelial ovarian cancer. Blood hemoglobin levels were determined before surgery and patients with values <12 g/dl were considered anemic. Data analysis included univariate and multiple Cox models. Tumor anemia was present in 143 (25.9%) patients before surgery. Tumor anemia was present in 143 (25.9%) patients before surgery. In a multivariate Cox model, pretreatment hemoglobin values proved to be an independent prognostic factor for patients with stage I-II epithelial ovarian cancer (n=203), but failed to attain significance in patients with stage III-IV disease (n=350). Tumor anemia defined as pretreatment hemoglobin values <12 g/dl may indicate patients with stage I and II epithelial ovarian cancer, who are at increased risk of relapse.


Subject(s)
Anemia/blood , Hemoglobins/analysis , Ovarian Neoplasms/blood , Ovarian Neoplasms/surgery , Adenocarcinoma, Mucinous/blood , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/surgery , Adult , Aged , Carcinoma/blood , Carcinoma/mortality , Carcinoma/surgery , Carcinoma, Endometrioid/blood , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/surgery , Female , Follow-Up Studies , Humans , Middle Aged , Multivariate Analysis , Neoplasm Staging , Ovarian Neoplasms/mortality , Predictive Value of Tests , Proportional Hazards Models , Retrospective Studies , Time Factors
19.
J Neurosurg ; 94(5): 846-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11354422

ABSTRACT

Only five patients found to have brain metastasis preceding the diagnosis of endometrial cancer have been reported in the literature, and none of these survived beyond 38 months. The authors report on two patients with primary endometrial cancer who initially presented with cerebral metastasis. One of these patients died of disease 15 months after diagnosis. The other patient is still alive, with no evidence of disease, 171 months after she underwent radiosurgery for a solitary brain metastasis, aggressive cytoreductive abdominal and pelvic surgery, and doxorubicin-based chemotherapy. To the best of their knowledge, the authors believe that no similar observation has been made for any primary gynecological neoplasm, including endometrial, ovarian, or cervical cancer. This is the first report documenting that survival beyond one decade may be achieved after intensive multimodal therapy in selected patients in whom a solitary brain metastasis has been found before diagnosis of endometrial cancer. Aggressive therapy appears to be warranted in these patients.


Subject(s)
Brain Neoplasms/secondary , Endometrial Neoplasms/pathology , Brain Neoplasms/surgery , Brain Neoplasms/therapy , Combined Modality Therapy , Fatal Outcome , Female , Humans , Middle Aged , Treatment Outcome
20.
Anticancer Res ; 21(5): 3729-32, 2001.
Article in English | MEDLINE | ID: mdl-11848553

ABSTRACT

BACKGROUND: Ovarian cancer continues to be the leading cause of death due to gynecologic malignancies and most patients still present with advanced disease. In the present study we evaluated long-term survival and prognostic factors in patients with stage IV ovarian cancer. PATIENTS AND METHODS: The charts of 62 consecutive women with FIGO stage IV epithelial ovarian cancer were reviewed. RESULTS: Chemotherapy was the only factor associated with longer survival. Three patients (5%) survived for longer than 5 years. One died of disease at 6.3 years and two are alive without evidence of disease at 12.4 and 14.9 years, respectively. CONCLUSION: Survival seemed to correlate with the possibility of administering chemotherapy. Patients with verified stage IV ovarian cancer, in whom due to the initial tumor load, operative extent and concomitant illness, the possibility of postoperative chemotherapy administration seems questionable, might be considered for primary chemotherapy followed by surgery.


Subject(s)
Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Adult , Aged , Female , Humans , Middle Aged , Neoplasm Staging , Prognosis , Survival Rate
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