[Show abstract][Hide abstract] ABSTRACT: Interleukin-1 (IL-1) is a cytokine critical to inflammation, immunological activation, response to infection, and bone marrow hematopoiesis. Cyclophosphamide downmodulates immune suppressor cells and is cytotoxic to a variety of tumors. A phase I trial of IL-1 and cyclophosphamide was conducted by the Eastern Cooperative Oncology Group. This study evaluated 3 dose levels and 3 schedules in patients with solid tumors. The goal was to evaluate the hematopoietic supportive care effect and possible antitumor effect. Toxicity was fever, chills, hypotension, nausea/emesis, hepatic, and neutropenia. Toxicity increased with dose increases of interleukin-1. Treatment at all dose levels resulted in significant increases in total white blood cell (WBC) counts above baseline. Nadir WBC and nadir absolute neutrophil counts were not significantly different by dose level of IL-1 or schedule of IL-1. Toxicity due to IL-1 at higher doses prohibited further evaluation of this agent for hematopoietic support, particularly in view of the activity and tolerability of more lineage-specific hematopoietic cytokines. Therapeutic interventions in the role of IL-1 in inflammatory conditions and cancer may be further informed by our definition of its clinical and biological effects in this evaluation of dose and schedule.
Preview · Article · Jan 2014 · Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research
[Show abstract][Hide abstract] ABSTRACT: Despite advances in the care of patients with cancer over the last 10 years, cancer remains the second leading cause of death in the United States. Many patients receive aggressive, in-hospital end-of-life care at high cost. There are few data on outcomes after unplanned hospitalization of patients with metastatic cancer.
In 2000 and 2010, data were collected on admissions, interventions, and survival for patients admitted to an academic inpatient medical oncology service.
The 2000 survey included 191 admissions of 151 unique patients. The 2010 survey assessed 149 admissions of 119 patients. Lung, GI, and breast cancers were the most common cancer diagnoses. In the 2010 assessment, pain was the most common chief complaint, accounting for 28%. Although symptoms were the dominant reason for admission in 2010, procedures and imaging were common in both surveys. The median survival of patients after discharge was 4.7 months in 2000 and 3.4 months in 2010. Despite poor survival in this patient population, hospice was recommended in only 23% and 24% of patients in 2000 and 2010, respectively. Seventy percent of patients were discharged home without additional services.
On the basis of our data, an unscheduled hospitalization for a patient with advanced cancer strongly predicts a median survival of fewer than 6 months. We believe that hospital admission represents an opportunity to commence and/or consolidate appropriate palliative care services and end-of-life care.
Full-text · Article · May 2013 · Journal of Oncology Practice
[Show abstract][Hide abstract] ABSTRACT: Following demonstrations of success of interactive cancer communication systems (ICCS) for patients, the challenge and opportunity
are to integrate such systems with human resources. A randomized trial explored relative benefits of an ICCS, a human cancer
information mentor, and a condition combining both. Women with breast cancer (N = 434) were randomized to have access to a tested ICCS (CHESS, the Comprehensive Health Enhancement Support System), a human
cancer information mentor, both interventions, or a control condition providing a computer, training, and Internet access.
Both a human mentor and an ICCS version improved health information competence and emotional processing over the Internet
control, and the combined condition exceeded either alone. Integrating human and computer-based resources for breast cancer
patients benefits them more than either alone.
KeywordsBreast cancer–eHealth–Quality of life–Interpersonal communication
Full-text · Article · Mar 2011 · Translational Behavioral Medicine
[Show abstract][Hide abstract] ABSTRACT: Little is known about the effective elements of Interactive Cancer Communication Systems (ICCSs). A randomized trial explored which types of services of a multifaceted ICCS benefited patients and the nature of the benefit. Women with breast cancer (N=450) were randomized to different types of ICCS services or to a control condition that provided internet access. The Comprehensive Health Enhancement Support System (CHESS), served as the ICCS. ICCS services providing information and support, but not coaching such as cognitive behavior therapy, produced significant benefits in health information competence and emotional processing. Provision of Information and Support ICCS services significantly benefited women with breast cancer. More complex and interactive services designed to train the user had negligible effects.
[Show abstract][Hide abstract] ABSTRACT: MicroRNAs regulate diverse cellular processes and play an integral role in cancer pathogenesis. Genomic variation within miRNA target sites may therefore be important sources for genetic differences in cancer risk. To investigate this possibility, we mapped HapMap single nucleotide polymorphisms (SNP) to putative miRNA recognition sites within genes dysregulated in estrogen receptor-stratified breast tumors and used local linkage disequilibrium patterns to identify high-ranking SNPs in the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer genome-wide association study for further testing. Two SNPs, rs1970801 and rs11097457, scoring in the top 100 from the CGEMS study, were in strong linkage disequilibrium with rs1434536, an SNP that resides within a miR-125b target site in the 3' untranslated region of the bone morphogenic receptor type 1B (BMPR1B) gene encoding a transmembrane serine/threonine kinase. We validated the CGEMS association findings for rs1970801 in an independent cohort of admixture-corrected cases identified from families with multiple case histories. Subsequent association testing of rs1434536 for these cases and CGEMS controls with imputed genotypes supported the association. Furthermore, luciferase reporter assays and overexpression of miR-125b-mimics combined with quantitative reverse transcription-PCR showed that BMPR1B transcript is a direct target of miR-125b and that miR-125b differentially regulates the C and T alleles of rs1434536. These results suggest that allele-specific regulation of BMPR1B by miR-125b explains the observed disease risk. Our approach is general and can help identify and explain the mechanisms behind disease association for alleles that affect miRNA regulation.
[Show abstract][Hide abstract] ABSTRACT: Purpose Reirradiation of breast cancer locoregional recurrence (LRR) in the setting of prior post-mastectomy radiation poses a significant
clinical challenge due to the high risk for severe toxicity. In an attempt to reduce these toxicities, we have developed pulsed
reduced dose-rate radiotherapy (PRDR), a reirradiation technique in which a series of 0.2Gy pulses separated by 3-min time
intervals is delivered, creating an apparent dose rate of 0.0667Gy/min. Here we describe our early experience with PRDR.
Patients and methods We reirradiated 17 patients with LRR breast cancer to the chest wall, axilla, or supraclavicular region using PRDR. The median
prior radiation dose was 60Gy. We delivered a median PRDR dose of 54Gy (range 40–66Gy) in 1.8–2.0Gy per fraction. Eight
patients received concomitant low dose capecitabine for radiosensitization. The median treatment volume was 2,084cm3 (range 843–7,881cm3). Results At a median follow-up of 18months (range 4–75months) only 2 patients have had tumor failure in the treatment region. Estimated
2-year local control rate is 92%. Treatment was well tolerated with 4 patients experiencing grade 3 acute skin toxicity. Despite
a median cumulative dose of 110Gy (range 80–236Gy), there has been only one grade 3 and one grade 4 late toxicity. Conclusions With a median follow-up of 18months, PRDR appears to be an effective method to reirradiate large volumes of previously irradiated
tissue in selected patients with locoregional chest wall, axilla, and supraclavicular recurrences.
No preview · Article · Mar 2009 · Breast Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, re-sequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's chi(2) = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's chi(2) = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (pi = 0.0072, Tajima's D = 3.31, 14 SNPs) and the Japanese (pi = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer.
[Show abstract][Hide abstract] ABSTRACT: Perillyl alcohol (POH) is a naturally occurring lipid with preclinical activity against mammary carcinomas. We conducted a phase II multi-institutional study of oral POH administered four times daily in women with advanced treatment-refractory breast cancer.
Eligible women were treated with POH four times daily at 1,200-1,500 mg m(-2) dose(-1) on a 28-day cycle. Patients tolerating 1,200 mg m(-2) day(-1) four times daily after one cycle were dose-escalated to 1,500 mg/m(2). The primary endpoint was 1-year freedom-from-progression (FFP) rate. Secondary endpoints were response rate, tolerability and correlative evaluations.
Twenty-nine cycles of POH were administered to 14 women. Three patients were dose-escalated to 1,500 mg/m(2). Grade 1 and grade 2 gastrointestinal effects and fatigue were predominant toxicities. Of seven patients receiving up to one cycle, three stopped therapy due to intolerance. Only two patients received more than two cycles, with disease stabilization of 3 and 8 months. Thirteen patients were evaluable for response. One-year FFP rate was zero. No objective responses were seen. The median time to progression was 35 days (95% CI, 29-123 days). Median overall survival was 389 days (95% CI, 202-776 days). Pharmacokinetic parameters were similar to previous investigations. The ability to correlate plasma TGF-beta1 levels with outcome was limited by lack of clinical benefit and inter- and intra-patient variability.
Enrollment was suspended short of planned accrual because of lack of response and poor tolerance to POH. This regimen does not appear to provide benefit in advanced treatment-refractory breast carcinoma.
No preview · Article · Jul 2008 · Cancer Chemotherapy and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: To compare the benefits of the Internet generally versus a focused system of services, 257 breast cancer patients were randomly assigned to a control group, access to the Internet with links to high-quality breast cancer sites, or access to an eHealth system (Comprehensive Health Enhancement Support System, CHESS) that integrated information, support, and decision and analysis tools. The intervention lasted 5 months, and self-report data on quality of life, health-care competence, and social support were collected at pretest and at 2-, 4-, and 9-month posttests. CHESS subjects logged on more overall than Internet subjects and accessed more health resources, but the latter used non health-related sites more. Subjects with access to the Internet alone experienced no better outcomes than controls at any of the 3 time points, compared to pretest levels. Subjects with CHESS experienced greater social support during the intervention period and had higher scores on all 3 outcomes at 9 months, 4 months after the intervention ended. CHESS subjects also scored higher than those with Internet access during the intervention period but not significantly after the intervention ended. Thus, CHESS (with one simple interface and integrated information, communication, and skills services) helped newly diagnosed breast cancer patients even after computers were removed. In contrast, patients received little benefit from Internet access, despite having links to a variety of high-quality sites.
Full-text · Article · Jun 2008 · Journal of Communication
[Show abstract][Hide abstract] ABSTRACT: To assess the activity and toxicity of valspodar (PSC-833) in combination with paclitaxel in women with anthracycline refractory, metastatic breast cancer.
Limited, multi-institutional, Phase II trial of valspodar at 5 mg/kg/dose orally every 6 hours for 12 doses in combination with paclitaxel 70 mg/m2 administered intravenously as a 3-hour infusion beginning 4 hours after the fifth dose of valspodar, every 3 weeks. Eligible patients had bi-dimensionally measurable metastatic carcinoma of the breast, prior anthracycline therapy or a medical contraindication to anthracycline therapy, no more than one prior chemotherapy for recurrent or metastatic breast cancer, and adequate organ function. Treatment was continued until disease progression or unacceptable toxicity.
Thirty-four patients are evaluable for response and 37 for toxicity. Two (6 percent) patients achieved a complete response and 5 (15 percent) a partial response for an objective response rate of 21 percent (95 percent confidence interval of 9 to 38 percent). Median duration of response was 9.7 months (95 percent confidence interval 8.0-17.2 months), median time to progression was 3.3 months (95 percent confidence interval 2.0-4.2 months), and median survival was 12 months (95 percent confidence interval 8.1-17.3 months). The toxicity experienced was acceptable.
Combination valspodar plus paclitaxel is an active regimen and has acceptable toxicity. The combination is not clearly more active than single agent paclitaxel.
No preview · Article · Dec 2006 · Cancer Investigation
[Show abstract][Hide abstract] ABSTRACT: Over a recent 3-month period in our oncology practice, we became aware of multiple patients reporting domestic abuse. We present three selected cases, review the literature on domestic violence, and explore issues of diagnosis and management in a cancer population. Domestic violence against cancer patients may be more common than initially appreciated, and further awareness and research are indicated.
Preview · Article · Feb 2006 · The journal of supportive oncology
[Show abstract][Hide abstract] ABSTRACT: The purpose of this multicenter phase II trial was to evaluate the clinical activity of topotecan as first-line chemotherapy in patients with metastatic breast cancer and previous exposure to adjuvant doxorubicin.
Patients with measurable disease received a 72-hour continuous intravenous infusion of topotecan 1.3 mg/m(2) per day repeated every 21 days. The primary objective was to determine whether > or = 4 responses were observed among 30 evaluable patients after 3 cycles of therapy using a 2-stage design (> or = 2 responses required in the first 20 evaluable patients). Duration of response, time to tumor progression, overall survival, and toxicity were also examined. Thirty-five patients altogether received 78 cycles of therapy (median, 3 cycles; range, 1-8 cycles).
Two partial responses (6%; 95% confidence interval, 0.7%-19%) were observed among 30 evaluable patients (median age, 55 years; range, 34-76 years; median Eastern Cooperative Oncology Group performance status, 0; range, 0-2). Median time to progression and overall survival were 2.3 months and 18.7 months, respectively. Myelosuppression was the most common toxicity among 34 evaluable patients (grade 3/4 neutropenia and thrombocytopenia in 62% and 53%, respectively) with only 1 life-threatening event.
Although tolerable, this dose and schedule of topotecan has limited activity in unselected patients with breast cancer even as first-line therapy. Identification of potential predictive markers of response and toxicity is encouraged before considering further studies of topotecan and camptothecin analogues in breast cancer.
No preview · Article · Nov 2005 · Clinical Breast Cancer
[Show abstract][Hide abstract] ABSTRACT: We conducted linkage analysis of 80 candidate genes in 201 brother pairs affected with prostatic adenocarcinoma. Markers representing two adjacent candidate genes on chromosome 3p, CDC25A and FHIT, showed suggestive evidence for linkage with single-point identity-by-descent allele-sharing statistics. Fine-structure multipoint linkage analysis yielded a maximum LOD score of 3.17 (P = 0.00007) at D3S1234 within FHIT intron 5. For a subgroup of 38 families in which three or more affected brothers were reported, the LOD score was 3.83 (P = 0.00001). Further analysis reported herein suggested a recessive mode of inheritance. Association testing of 16 single nucleotide polymorphisms (SNP) spanning a 381-kb interval surrounding D3S1234 in 202 cases of European descent with 143 matched, unrelated controls revealed significant evidence for association between case status and the A allele of single nucleotide polymorphism rs760317, located within intron 5 of FHIT (Pearson's chi(2) = 8.54, df = 1, P = 0.0035). Our results strongly suggest involvement of germline variations of FHIT in prostate cancer risk.
[Show abstract][Hide abstract] ABSTRACT: Both surgical and nonsurgical options are available to treat bowel obstruction in patients with metastatic cancer. The goal is straightforward: to restore bowel patency and palliate the symptoms of obstruction. Yet the most appropriate management is often a challenging decision.
We sought to review our experience in managing patients with metastatic cancer and bowel obstruction.
A retrospective review was performed to identify all patients admitted at University of Wisconsin Hospital between 1993 and 2000 with the diagnoses of both bowel obstruction and metastatic cancer. Demographic data, type of management, postoperative complications, and outcome were analyzed.
A total of 114 patients with primarily colorectal or gynecologic malignancies were identified. Patients' first bowel obstructions were managed in one of two ways: (1) definitive surgical intervention (n = 47), or (2) conservative management (n = 67). The median overall survival was 3 mo for the entire study group. There was no significant difference in overall or obstruction-free survival based on management, presence of recurrent bowel obstruction, or type of primary cancer. The only factor that was significant in predicting poor overall survival included a disease-free interval of less than 1 yr (time of diagnosis of primary cancer to time of bowel obstruction, p = 0.002).
Bowel obstruction in patients with metastatic cancer is a terminal event, with a 3-mo median survival. Because there is no difference in overall or obstruction-free survival based on management, the treatment for palliation of bowel obstruction in patients with metastatic cancer should be individualized.
No preview · Article · Feb 2005 · International Journal of Gastrointestinal Cancer
[Show abstract][Hide abstract] ABSTRACT: Capecitabine is an oral fluoropyrimidine used for cancer treatment. It is generally well tolerated. A patient who had previously received adjuvant 5-fluorouracil without neurotoxicity had a severe adverse reaction when later given capecitabine in the metastatic setting. She presented with the acute onset of neuromuscular symptoms, the most prominent being trismus but also including slurred speech, confusion, gait abnormalities, and ocular changes. Her symptoms completely resolved with discontinuation of capecitabine.
No preview · Article · Sep 2003 · Clinical Colorectal Cancer
[Show abstract][Hide abstract] ABSTRACT: In vitro and clinical data suggest a therapeutic role for alpha2 interferon (IFN) in the treatment of the chronic myeloproliferative disorders. Accordingly, a multiinstitutional, Phase II trial of IFN in patients with agnogenic myeloid metaplasia (AMM), essential thrombocythemia (ET), and polycythemia rubra vera (PRV) in the spent phase was initiated. The objectives of this study were 1) to investigate the response rates that may be achieved with IFN in the treatment of patients with these disorders, 2) to estimate the durability of the responses, and 3) to assess the toxicities of IFN in these populations.
Enrollment was limited to patients with AMM, ET, or PRV who already had developed 1) anemia or transfusion dependency, 2) thrombocytosis uncontrolled by standard therapy, 3) hemostatic complications, or 4) symptomatic splenomegaly. Initially, patients were started on IFN at a dose of 5 MU/m(2) per day as a subcutaneous injection. After the first 16 patients had been treated, the starting dose of IFN was reduced to 2 MU/m(2) per day because of unexpected toxicities.
IFN demonstrated different levels of efficacy and toxicity in each of the three diseases studied. The overall response rates achieved among the evaluable patients in each category were as follows: ET, 88.2% (n = 17 patients; 1 complete response and 14 partial responses); PRV, 41.7% (n = 12 patients; 1 complete response and 4 partial responses); and AMM, 3.2% (n = 31 patients; 0 complete responses and 1 partial response). Thrombocytosis and leukocytosis were controlled in nearly all patients, with reversal of splenomegaly and resorption of myelofibrosis achieved in fewer patients. The toxicities attributed to IFN differed notably among the three disease groups: patients who had AMM suffered systemic and neurologic toxicities more frequently than patients who had PRV or ET; whereas patients who had ET experienced a greater than expected incidence of hepatic abnormalities, most typically transient elevations of serum amino acid transaminase levels.
The current study demonstrated the safety and efficacy of IFN in patients with ET, PRV, and AMM. Objective responses and/or disease stabilization were obtained in patients with all three disease entities, including the reversal of splenomegaly and resorption of myelofibrosis in some patients.
[Show abstract][Hide abstract] ABSTRACT: Evidence is accumulating for physical activity as an effective, well-tolerated, highly rewarding complementary behavioral intervention for enhancing quality of life (QOL) as well as fitness among individuals with chronic and even terminal illnesses. However, relatively few studies have examined the feasibility and potential health benefits of supervised, structured exercise programs for sedentary women with primary breast cancer. Forty women over the age of 45 with primary breast cancer participated in a course of group exercise training (GET) delivered in a structured format three times per week for 16 weeks. GET emphasizes physical activities that promote aerobic fitness, strength, and flexibility. Assessments of fitness/vigor and QOL were conducted prior to, during, and upon completion of the program. Results demonstrated that GET was feasible, safe, and well-tolerated. Moreover, the participants experienced significant health benefits over the course of the intervention in multiple dimensions of fitness/vigor (aerobic capacity, strength, flexibility) as well as QOL (increased positive affect, decreased distress, enhanced well-being, and improved functioning). Discussion highlights the need for inclusion of physical activity programs in comprehensive, complementary treatment regimes for breast cancer patients.
[Show abstract][Hide abstract] ABSTRACT: Fine-needle aspiration (FNA) is a diagnostic modality that continues to improve in accuracy as training and experience accumulate. With increasing operator expertise and improved localization techniques, greater numbers of patients are able to benefit from FNAs performed on sites that are otherwise difficult or dangerous to reach by conventional surgery. We present a retrospective review of a 2-yr experience with radiologically-guided deep-seated FNA. In 115 cases involving transthoracic and transabdominal sites, we achieved the following overall figures: 91.9% sensitivity, 100% specificity, 93.9% diagnostic accuracy, 100% positive predictive value, and 80.6% negative predictive value. Our results are compared to those in other series. When properly applied, FNA of deep-seated lesions through image guidance is equivalent to tissue diagnosis obtained by laparotomy or surgical procedures. The benefits of FNA with or without core biopsy vs. scalpel biopsy are readily apparent when one considers the morbidity, cost, turnaround time, and trauma to the patient.
No preview · Article · Jun 1998 · Diagnostic Cytopathology
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the clinical efficacy and safety of docetaxel (Taxotere) in patients with adenocarcinoma
of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy. Docetaxe1100 mg m−2 was administered as a 1 hour intravenous (IV) infusion every 3 weeks to 41 patients. Patients were premedicated prior to
each course with dexamethasone, diphenhydramine and cimetidine. Clinical response and toxicity were determined. Objective
responses were seen in seven of 41 eligible patients (two complete responses [CRs] and five partial responses [PRs], for an
objective response rate of 17% (90% confidence interval [CI], 8% to 30%). The most common toxicity was grade 4 neutropenia,
which occurred in 88% of patients; 46% of patients required a dose reduction following an episode of neutropenic fever requiring
antibiotic therapy. Additional patients have had reversible grade 3–4 toxicities including nausea, vomiting, stomatitis, diarrhea,
fatigue and peripheral neuropathy. Ten patients have had grade 1–3 hypersensitivity reactions. Alopecia has been seen in the
majority of patients. Fluid retention grade 1–3 has been observed in patients. Docetaxel administered on this schedule is
an active agent in adenocarcinomas of the upper gastrointestinal tract. Further investigation of this drug should be conducted
in multi-drug combination programs.
No preview · Article · May 1996 · Medical Oncology
[Show abstract][Hide abstract] ABSTRACT: Sixty-one ambulatory patients with advanced or unresectable renal carcinoma were treated with either melphalan (41 patients) or thioguanine (20 patients). Two objective partial responses were observed in the melphalan cohorts for a response rate of 4.9% (exact 95% confidence interval, 1–17%). No patients treated with thioguanine responded. One patient died of hemorrhage on the melphalan arm. There were no treatment-related deaths on the thioguanine arm. Other than the one death, there were no unexpected or irreversible toxicities. Myelosuppression was the most frequent toxicity. These agents have no meaningful activity in the treatment of advanced renal cell carcinoma.
No preview · Article · May 1996 · Urologic Oncology