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Daniel Zelterman

Publications and source records attributed to Daniel Zelterman.

18 recordsLinked to original sources
PubMed2006

Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer.

OBJECTIVES: This study evaluated the incidence of late cardiotoxicity after dose-dense and -intense adjuvant sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) for breast cancer (BC) with > or = 4 involved ipsilateral axillary lymph nodes. METHODS: Patients were enrolled from 1994 to 2001 after definitive BC surgery if > or =4 axillary nodes were involved. Planned treatment was A 90 mg/m(2) q 14 days x 3, T 250 mg/m(2) q 14 days x 3, C 3 g/m(2 )q 14 days x 3 with filgrastim (G) support. Left ventricular ejection fraction (LVEF) was monitored using equilibrium radionuclide angiography (ERNA) before the initiation of chemotherapy, and after three cycles of each chemotherapeutic agent. At a median follow-up of 7 years, we obtained ERNA scans on 32 patients to evaluate the long-term cardiotoxicity of this regimen. RESULTS: Eighty-five eligible patients enrolled on the treatment protocol. Clinical heart failure developed in one patient. Seven (8%) patients had LVEF < 50% at the end of therapy. No cardiac-related deaths occurred. Thirty-two (46%) of 69 surviving patients have consented to late cardiac imaging. At a median follow-up of 7 years, the median absolute change in LVEF from baseline was -5.5%; [range (-8%) to (+36%)], and from the end of chemotherapy was -2.0%; [range (-25%) to (+16%)]. Four patients (12%) had a LVEF < 50%; two of these four patients had an LVEF of < 50% at the end of chemotherapy. CONCLUSIONS: Late development of asymptomatic decline in cardiac function may occur after dose-dense and -intense adjuvant therapy, but is uncommon.

Aged↗
PubMed2006

Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential.

BACKGROUND: Methylation-mediated suppression of detoxification, DNA repair, and tumor suppressor genes has been implicated in cancer development and progression. Studies also have indicated that concordant methylation of multiple genes (methylator phenotypes), rather than a single gene, may predict cancer prognosis. The current study was designed to determine whether a methylator phenotype exists in ovarian cancer, whether methylation frequencies differ between malignant ovarian tumors and ovarian tumors with low malignant potential (LMP or borderline), and whether methylation of multiple genes affects patient survival. METHODS: The current study included 234 consecutively diagnosed patients with either LMP (n = 19 patients) or malignant (n = 215 patients) ovarian tumors. DNA samples were extracted from fresh frozen tissues and were analyzed for methylation in the promoter region of 6 genes (p16, breast cancer 1 [BRCA1], insulin-like growth factor-binding protein 3 [IGFBP-3], glutathione S-transferase pi 1 [GSTP1], estrogen receptor-alpha [ER-alpha], and human MutL homologue 1 [hMLH1]) by using methylation-specific polymerase chain reaction analysis. RESULTS: The frequencies of methylation in malignant tumors and LMP tumors were 0% and 0% for GSTP1, respectively; 9% and 0% for hMLH1, respectively; 21% and 5% for BRCA1, respectively; 42% and 21% for p16, respectively; 44% and 26% for IGFBP-3, respectively; and 57% and 42% for ER-alpha, respectively. A methylator phenotype was not detected, but a calculated methylation index (MI) that was based on the total number of genes methylated in each tumor was associated with ovarian cancer risk and progression. A higher MI was associated with malignant tumors (odds ratio, 10.11; 95% confidence interval [95% CI], 1.19-85.75) and disease progression (hazards ratio, 6.53; 95% CI, 1.39-30.65). CONCLUSIONS: Although a methylator phenotype was not identified, the current results suggested that methylation of multiple genes may play an important role in ovarian cancer development and progression and may have clinical implications in prognosis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database.

PURPOSE: To investigate the association between survival and postoperative radiotherapy (PORT) in patients with resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database, we selected patients with stage II or III NSCLC who underwent a lobectomy or pneumonectomy. Only those patients coded as receiving PORT or observation were included. To account for perioperative mortality, we excluded patients who survived less than 4 months. As a result of our inclusion criteria, we selected a total of 7,465 patients, with a median follow-up time of 3.5 years for patients still alive. RESULTS: Predictors for the use of PORT included age less than 50 years, higher American Joint Committee on Cancer stage, T3-4 tumor stage, larger tumor size, advanced node stage, greater number of lymph nodes involved, and a ratio of lymph nodes involved to lymph nodes sampled approaching 1.00. On multivariate analysis, older age, T3-4 tumor stage, N2 node stage, male sex, fewer sampled lymph nodes, and greater number of involved lymph nodes had a negative impact on survival. The use of PORT did not have a significant impact on survival. However, in subset analysis for patients with N2 nodal disease (hazard ratio [HR] = 0.855; 95% CI, 0.762 to 0.959; P = .0077), PORT was associated with a significant increase in survival. For patients with N0 (HR = 1.176; 95% CI, 1.005 to 1.376; P = .0435) and N1 (HR = 1.097; 95% CI, 1.015 to 1.186; P = .0196) nodal disease, PORT was associated with a significant decrease in survival. CONCLUSION: In a population-based cohort, PORT use is associated with an increase in survival in patients with N2 nodal disease but not in patients with N1 and N0 nodal disease.

Adult↗
PubMed2006

Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation.

BACKGROUND: Perforated necrotizing enterocolitis is a major cause of morbidity and mortality in premature infants, and the optimal treatment is uncertain. We designed this multicenter randomized trial to compare outcomes of primary peritoneal drainage with laparotomy and bowel resection in preterm infants with perforated necrotizing enterocolitis. METHODS: We randomly assigned 117 preterm infants (delivered before 34 weeks of gestation) with birth weights less than 1500 g and perforated necrotizing enterocolitis at 15 pediatric centers to undergo primary peritoneal drainage or laparotomy with bowel resection. Postoperative care was standardized. The primary outcome was survival at 90 days postoperatively. Secondary outcomes included dependence on parenteral nutrition 90 days postoperatively and length of hospital stay. RESULTS: At 90 days postoperatively, 19 of 55 infants assigned to primary peritoneal drainage had died (34.5 percent), as compared with 22 of 62 infants assigned to laparotomy (35.5 percent, P=0.92). The percentages of infants who depended on total parenteral nutrition were 17 of 36 (47.2 percent) in the peritoneal-drainage group and 16 of 40 (40.0 percent) in the laparotomy group (P=0.53). The mean (+/-SD) length of hospitalization for the 76 infants who were alive 90 days after operation was similar in the primary peritoneal-drainage and laparotomy groups (126+/-58 days and 116+/-56 days, respectively; P=0.43). Subgroup analyses stratified according to the presence or absence of radiographic evidence of extensive necrotizing enterocolitis (pneumatosis intestinalis), gestational age of less than 25 weeks, and serum pH less than 7.30 at presentation showed no significant advantage of either treatment in any group. CONCLUSIONS: The type of operation performed for perforated necrotizing enterocolitis does not influence survival or other clinically important early outcomes in preterm infants. (ClinicalTrials.gov number, NCT00252681.).

Birth Weight↗
PubMed2005

Evaluation of irinotecan plus paclitaxel in patients with advanced non-small cell lung cancer.

PURPOSE: We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel in patients with advanced stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were eligible if they had histologically confirmed chemotherapy naïve stage IV NSCLC or stage IIIB disease that was not suitable for combined modality therapy. Patients were treated with irinotecan 50 mg/m2 and paclitaxel 75 mg/m2 on days 1 and 8 of a 21-day cycle. If the patient did not experience >grade 1 toxicity during the first cycle, the dose of irinotecan could be escalated to 60 mg/m(2). Patients were evaluated for tumor response rate, time to progression (TTP), overall survival (OS) and toxicity. RESULTS: Twenty-three eligible patients were treated. Two (9%) patients achieved a partial response. Eight patients (35%) had stable disease. The median number of cycles given per patient was four (range 1-29). The major toxicities were grade >or=3 neutropenia (26%) and grade 3 diarrhea (5%). The median time to progression was 2.8 months (range 0.5-21.8 months) for all patients and 4.3 months for the patients who had either stable disease or a partial response. The median overall survival was 9.2 months (range 0.5-40 months). The one- and two-year survival rates were 39% and 13%, respectively. CONCLUSION: The combination of irinotecan and paclitaxel is safe in advanced NSCLC and affords a survival similar to other non-platinum as well as platinum-based doublets. However, this combination does not have sufficient activity to justify further study in an unselected population. If biomarkers are developed that can guide the selection of chemotherapy in an individual patient, there may be a rationale for further evaluation of this regimen.

Aged↗
PubMed2005

Five-year update of an expanded phase II study of dose-dense and -intense doxorubicin, paclitaxel and cyclophosphamide (ATC) in high-risk breast cancer.

OBJECTIVES: This study evaluated the safety and efficacy of dose-dense and -intense sequential doxorubicin (A), paclitaxel (T) and cyclophosphamide (C) as adjuvant therapy for breast cancer (BC) with >or=4 ipsilateral axillary lymph nodes. METHODS: Patients were recruited after BC surgery if >or=4 axillary nodes were involved by metastatic cancer. Planned treatment was A 90 mg/m(2) three times every 14 days (q14d x 3), T 250 mg/m(2) q14d x 3 and C 3 g/m(2) q14d x 3 combined with filgrastim support. RESULTS: The study enrolled 85 eligible patients. The median number of lymph nodes involved was 9. Mean dose intensity was >94% of planned for each drug. Common grade 3 toxicities included nausea and/or vomiting (24%), mucositis (18%), neuropathy (16%), palmar-plantar erythrodysesthesia (12%), myalgia (6%) and arthralgia (6%). Grade 3/4 neutropenia occurred in 77 (91%) patients, and 32 (38%) patients had neutropenic fever. One patient developed acute leukemia. Sixty-nine (81%) patients are alive, and 59 (69%) patients are alive and free of distant disease at a median follow-up of 5 years. CONCLUSIONS: ATC is a feasible regimen for adjuvant therapy of high-risk BC, with a relatively low rate of relapse at the 5-year follow up.

Adult↗
PubMed2005

A randomized controlled trial of meditation and massage effects on quality of life in people with late-stage disease: a pilot study.

CONTEXT: Certain meditation practices may effectively address spiritual needs near end-of-life, an often overlooked aspect of quality of life (QOL). Among people subject to physical isolation, meditation benefits may be blunted unless physical contact is also addressed. OBJECTIVE: To evaluate independent and interactive effects of Metta meditation and massage on QOL in people with acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized controlled blinded factorial pilot trial conducted from November 2001 to September 2003. SETTING: An AIDS-dedicated skilled nursing facility in New Haven, Connecticut. PARTICIPANTS: Fifty-eight residents (43% women) with late stage disease (AIDS or comorbidity). INTERVENTIONS: Residents were randomized to 1 month of meditation, massage, combined meditation and massage, or standard care. The meditation group received instruction, then self-administered a meditation audiocassette daily. A certified massage therapist provided the massage intervention 30 minutes per day 5 days per week. OUTCOME MEASURE: Changes on Missoula-Vitas QOL Index overall and transcendent (spiritual) scores at 8 weeks. RESULTS: The combined group showed improvement in overall (p = 0.005) and transcendent (p = 0.01) scores from baseline to 8 weeks, a change significantly greater (p < 0.05) than the meditation, massage, and control groups. CONCLUSIONS: The combination of meditation and massage has a significantly favorable influence on overall and spiritual QOL in late-stage disease relative to standard care, or either intervention component alone.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Atrial fibrillation after cardiac surgery/cardiopulmonary bypass is associated with monocyte activation.

Atrial fibrillation (AF) contributes significantly to morbidity and mortality in as many as one-third of patients after cardiac surgery that requires cardiopulmonary bypass (CPB). Recent data suggest that inflammatory infiltration of the myocardium may predispose to AF. We conducted an exploratory pilot study to determine if there was an association between the perioperative leukocyte inflammatory response to cardiac surgery/CPB and postoperative AF. We enrolled 72 patients undergoing cardiac surgery with CPB; all patients were in sinus rhythm before surgery. Leukocyte activation (CD11b upregulation) was perioperatively measured in monocytes and neutrophils (PMN). Preoperative C-reactive protein (CRP) and perioperative neutrophil myeloperoxidase (MPO) were also monitored for inflammation, and troponin I was assayed for perioperative cardiac muscle damage. All markers were evaluated for differences between the subset of patients who developed AF versus those who remained in normal sinus rhythm after surgery. All 72 patients completed the study. Postoperative AF developed in 26 (36%) patients. Perioperative monocyte CD11b upregulation was significantly increased in patients who developed AF (P = 0.01), but increases in PMN CD11b were not significantly associated with AF (P = 0.057). The increase in both monocyte and PMN counts after aortic cross-clamp release was significantly associated with postoperative AF (P = 0.007 and P = 0.005, respectively). By contrast, preoperative CRP and perioperative MPO did not differ between AF and normal rhythm patients. Similarly, the peak value of troponin I did not differ between groups. In this pilot study of cardiac surgery/CPB patients, perioperative upregulation of the monocyte adhesion receptor, CD11b, and higher circulating monocyte and PMN numbers were associated with postoperative AF, suggesting that the induction of cellular inflammation during cardiac surgery/CPB may contribute to this pathophysiology.

Aged↗
PubMed2004

Total parenteral nutrition induced liver pathology: an autopsy series of 24 newborn cases.

Total parenteral nutrition (TPN)-induced liver injury is a common complication in neonates managed with newborn intensive care. In several of these cases, irreversible and even fatal liver damage may develop, with patients dying of liver failure. In spite of multiple studies over several years, the pathogenesis of TPN-induced liver damage remains poorly understood. Clinical data from 24 neonates with clinical history of receiving TPN who died at Yale-New Haven Children's Hospital and had autopsies performed, were collected by medical record review without knowledge of liver pathology findings. Liver histological sections from these patients were evaluated for multiple parameters without knowledge of the clinical course. Continuous data were analyzed by Wilcoxon signed-rank test and Mann-Whitney test, and dichotomous data by Fisher's exact test; P < 0.05 was considered significant. Different histopathological abnormalities with varying degrees of severity were observed. A progression in the severity of histopathological changes in relation to duration of TPN administration (DTPN) was found. While patients with DTPN of < 2 wk had no fibrosis or only mild degrees of fibrosis, patients with more than 6 wk of DTPN developed moderate-to-severe fibrosis. Similar results were observed for cholestasis and bile duct proliferation. We did not find significant differences for birth weight, gestational age, occurrence of necrotizing enterocolitis, sepsis, or enteral feedings between the group with normal-to-mild liver changes ( n = 16), and the group with moderate-to-severe liver changes ( n = 8). On the other hand, DTPN was significantly different between these two groups ( P = 0.008). Also, patients small for gestational age ( P = 0.003) and patients with bronchopulmonary dysplasia ( P = 0.001) were more commonly seen in the group with moderate-to-severe histopathological findings. Intracellular copper was detected in 12.5% of patients with moderate-to-severe liver changes, and was found in 50% of patients with normal-to-mild liver findings ( P = 0.04). Detection of copper from tissue sections also decreased with DTPN, being observed in 57% of patients with < 2 wk DTPN and in none of the patients with > 12 wk DTPN. Our findings confirm the known significant relationship between the duration of TPN and liver injury. While previously described associations with birth weight, gestational age, enteral feedings, necrotizing enterocolitis, and sepsis were not noted, our study suggests that poor intrauterine growth may be a significant clinical risk factor for TPN-induced liver injury. In addition, our findings suggest that copper may have a protective effect against the development of TPN-induced liver damage.

Copper↗
PubMed2003

An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells.

To develop a method to overcome the anergy that exists in tumor hosts to cancer, we have designed an adenoviral vector for the in vivo activation and tumor antigen loading of dendritic cells. This adenoviral vector encodes a fusion protein composed of an amino-terminal tumor-associated antigen fragment fused to the CD40 ligand (CD40L). Subcutaneous injection of an adenoviral vector encoding a fusion protein of the human papillomavirus E7 foreign antigen linked to the CD40L generates CD8+ T cell-dependent immunoresistance to the growth of the E7-positive syngeneic TC-1 cancer cells in C57BL/6 mice for up to 1 year. We also studied the s.c. injection of a vector carrying the gene for the human MUC-1 (hMUC-1) self-antigen fused to the CD40L. When this vector was injected into hMUC-1.Tg mice, which are transgenic for the hMUC-1 antigen, the growth of syngeneic hMUC-1-positive LL1/LL2hMUC-1 mouse cancer cells was suppressed in 100% of the injected animals. The hMUC-1.Tg mice are anergic to the hMUC-1 antigen before the injection of the vector. These experimental results show that it is possible to use vector injection to activate a long-lasting cellular immune response against self-antigens in anergic animals. The vector-mediated in vivo activation, and tumor-associated antigen loading of dendritic cells does not require additional cytokine boosting to induce the immune response against the tumor cells. This vector strategy may therefore be of use in the development of immunotherapy for the many carcinomas in which the hMUC-1 antigen is overexpressed.

Adenoviridae↗
PubMed2003

Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary.

OBJECTIVE: To analyze the long-term effects on reproductive function of fertility-preserving treatment for malignant germ cell tumors of the ovary. METHODS: A case series analysis was performed on patients with malignant germ cell tumors of the ovary seen or consulted on at our institution between 1975 and 1995. Follow-up information regarding reproductive function was obtained by a mailed or telephone questionnaire. RESULTS: A total of 106 patients with malignant germ cell tumors of the ovary were included in the study. Twenty patients were excluded because of loss of follow-up or death. For the remaining 86 patients, the median follow-up was 122 months (24-384 months). Fertility-preserving surgery was performed in 64 patients. Thirty-eight have attempted conception and 29 have achieved at least one pregnancy (76%). Among the patients who conceived, 20 were International Federation of Gynecology and Obstetrics (FIGO) stage I, one was stage II, and eight were stage III. Sixteen received vincristine, actinomycin D, and cyclophosphamide; three received cisplatin, vinblastine, and bleomycin; three received bleomycin, etoposide, and cisplatin; one received etoposide and cisplatin; four did not receive any chemotherapy; and two were treated with other combinations. Among the nine patients who could not conceive, seven were FIGO stage I and two were stage III. Four of these patients received vincristine, actinomycin D, and cyclophosphamide; three received etoposide and cisplatin; one received cisplatin, vinblastine, and bleomycin; and one patient received no chemotherapy. A total of 38 children were born to these women. Follow-up was available for 16 of these children, who have no evidence of congenital anomalies. CONCLUSION: Fertility-preserving surgery followed by chemotherapy, even in advanced-stage malignant germ cell tumors of the ovary, is effective in conserving the reproductive function of women with malignant germ cell tumors of the ovary.

Adolescent↗
PubMed2003

Analyzing multiply matched cohort studies with two different comparison groups: application to pregnancy rates among HIV+ women.

We develop a new statistical method to analyze multiply matched cohort studies with two different comparison groups. We employ a linear-logistic model to describe the underlying log-odds ratios and use a conditional likelihood approach to conduct inference. Under the assumption of homogeneous log-odds ratios, we provide methods to construct both asymptotic and exact confidence regions of the two log-odds ratios in a simple case. We propose a score test to evaluate the assumption of homogeneous log-odds ratios across strata. While our methods are general, we develop them around a specific application, namely, the study of pregnancy rates in HIV-infected women. Our analyses suggest that HIV infection is associated with a decrease in pregnancy rates and that this decrease in fertility becomes significant after accounting for illicit drug use.

Biometry↗
PubMed2002

Pregnancy and birth rates among HIV-infected women in the United States: the confounding effects of illicit drug use.

OBJECTIVE: To determine the effect of HIV infection on pregnancy and birth rates and assess the potentially confounding effect of illicit drug use. DESIGN: A retrospective record review of matched cohorts examining pregnancy outcomes for HIV-positive women and two HIV-negative comparison groups (one matched by drug use). METHODS: Ninety HIV-positive women who gave birth in a US city between 1989 and 1993 were matched to HIV-negative women by race, age, parity and date of index birth (group 1, N = 180) and also by the type of illicit drug used (group 2, N = 90). Data were abstracted on tubal ligations and pregnancies occurring before April 1996. RESULTS: A total of 63% of HIV-positive women used cocaine during the index pregnancy and 26% also used opiates. HIV-positive women had fewer tubal ligations than group 1 (38.9% versus 51.1%, P = 0.058), but there was no difference when matching included drug use (38.9% in group 2). HIV infection was associated with a decrease in the number of pregnancies; this decrease was most marked when matching included drug use (18.0 versus 32.1 pregnancies per 100 woman-years,P < 0.01). There were no significant differences in spontaneous or therapeutic terminations. Poisson regression analysis demonstrated that HIV infection and older age were associated with fewer pregnancies, and cocaine use with an increased pregnancy rate. CONCLUSION: This study confirms that HIV infection is associated with a decrease in the number of pregnancies, but also illustrates the confounding effects of illicit drug use among women in the United States.

Adult↗
PubMed2002

Statistical inference for familial disease clusters.

In many epidemiologic studies, the first indication of an environmental or genetic contribution to the disease is the way in which the diseased cases cluster within the same family units. The concept of clustering is contrasted with incidence. We assume that all individuals are exchangeable except for their disease status. This assumption is used to provide an exact test of the initial hypothesis of no familial link with the disease, conditional on the number of diseased cases and the distribution of the sizes of the various family units. New parametric generalizations of binomial sampling models are described to provide measures of the effect size of the disease clustering. We consider models and an example that takes covariates into account. Ascertainment bias is described and the appropriate sampling distribution is demonstrated. Four numerical examples with real data illustrate these methods.

Adult↗
PubMed2002

Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines.

Human papillomavirus (HPV) vaccines have the potential to prevent cervical cancer by preventing HPV infection or treating premalignant disease. We previously showed that DNA vaccination with the cottontail rabbit papillomavirus (CRPV) E6 gene induced partial protection against CRPV challenge and that the vaccine's effects were greatly enhanced by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, two additional strategies for augmenting the clinical efficacy of CRPV E6 vaccination were evaluated. The first was to fuse a ubiquitin monomer to the CRPV E6 protein to enhance antigen processing and presentation through the major histocompatibility complex class I pathway. Rabbits vaccinated with the wild-type E6 gene plus GM-CSF or with the ubiquitin-fused E6 gene formed significantly fewer papillomas than the controls. The papillomas also required a longer time to appear and grew more slowly. Finally, a significant proportion of the papillomas subsequently regressed. The ubiquitin-fused E6 vaccine was significantly more effective than the wild-type E6 vaccine plus GM-CSF priming. The second strategy was to vaccinate with multiple CRPV early genes to increase the breadth of the CRPV-specific response. DNA vaccines encoding the wild-type CRPV E1-E2, E6, or E7 protein were tested alone and in all possible combinations. All vaccines and combinations suppressed papilloma formation, slowed papilloma growth, and stimulated subsequent papilloma regression. Finally, the two strategies were merged and a combination DNA vaccine containing ubiquitin-fused versions of the CRPV E1, E2, and E7 genes was tested. This last vaccine prevented papilloma formation at all challenge sites in all rabbits, demonstrating complete protection.

Animals↗
PubMedDate not supplied

Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen.

OBJECTIVE: Considerable controversy surrounds the issue of whether estrogen influences cognitive function in postmenopausal women, and the results are far from consistent. For the most part, the cognitive processes studied have involved memory; to our knowledge, no previous studies have specifically examined the effects of estrogen on women's reading ability. DESIGN: To investigate reading and short-term memory in postmenopausal women treated with conjugated equine estrogens, we carried out a randomized, double-blind, placebo-controlled trial of 21 days in 60 midlife, postmenopausal women aged 32.8 to 64.9 years (mean 51.2 years, SD 5.0 years). Women were evaluated for oral reading measured by Gray Oral Reading Tests (third edition) and for verbal memory using immediate and delayed recall on the Logical Memory and Paired Associate Learning subtests of the Wechsler Memory Scale and by a Sentence Span task. RESULTS: The group receiving daily treatment with conjugated equine estrogens (Premarin, 1.25 mg; Wyeth-Ayerst Labs, Philadelphia, PA, USA) showed better oral reading and verbal memory performance than the placebo group. CONCLUSION: Estrogen may have positive effects on oral reading and verbal memory in midlife, postmenopausal women.

Adult↗
PubMedDate not supplied

Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer.

Background. Docetaxel and irinotecan have additive or synergistic activity in vitro and in vivo as well as differing toxicities and unique mechanisms of action. We conducted a phase I trial to determine the maximum-tolerated dose of docetaxel and irinotecan given on a weekly schedule. Methods. Eligible patients had advanced, incurable, solid tumors. Docetaxel was administered as a 1-hour infusion and escalated over four dose levels (25, 30, 35, and 40 mg/m(2)) followed by irinotecan administered over 30 minutes at a fixed dose of 50 mg/m(2). Treatment was administered weekly for four weeks followed by two weeks of rest. To improve tolerability, the schedule was modified to weekly administration for two weeks with one week of rest, and irinotecan was escalated over 3 dose levels (55, 60, and 65 mg/m(2)) with docetaxel fixed at 35 mg/m(2). Results. Forty-four patients were treated and the most common dose-limiting toxicity was diarrhea observed in 11% of patients. Severe neutropenia was rare (grade 4: 2%, grade 3: 23%). Other nonhematologic toxicities included nausea/vomiting, dehydration and fatigue. Partial responses occurred in two patients with pancreatic cancer, and one patient each with non-small cell lung and esophageal cancer. Conclusions. Weekly docetaxel and irinotecan is a promising non-cisplatin doublet with preliminary evidence of activity in advanced solid tumors. Diarrhea is the predominant dose-limiting toxicity but unlike the every 3 weeks schedule myelosuppression is modest. The recommended phase II doses are docetaxel 35 mg/m(2) and irinotecan 60 mg/m(2) on days 1 and 8 of a 21-day schedule. Phase II trials of this regimen are ongoing or planned in lung, head and neck, stomach, esophageal, and pancreatic cancers.

Adult↗