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Biomedical subjects

Jennifer Garst

Publications and source records attributed to Jennifer Garst.

15 recordsLinked to original sources
PubMed2007

Safety of topotecan in the treatment of recurrent small-cell lung cancer and ovarian cancer.

The topoisomerase I inhibitor, topotecan, is approved for the treatment of recurrent small-cell lung cancer (SCLC) and ovarian cancer (OC). Patients with recurrent SCLC and OC typically experience multiple relapses and receive multiple rounds of chemotherapy. In these settings, disease stabilisation is considered a treatment benefit, and quality-of-life effects and cumulative toxicities of treatments should be considered. Many patients with recurrent cancer may be predisposed to treatment-related adverse events because of advanced age, renal impairment or extensive prior therapy. The standard regimen of topotecan, 1.5 mg/m(2) on days 1-5 of a 21-day cycle, has generally mild nonhaematological toxicity and a well-defined haematological toxicity profile characterised by reversible and noncumulative neutropenia. Alternative regimens may lower the incidence of haematological toxicities and maintain antitumour efficacy. Topotecan may provide physicians with a versatile therapeutic option for the treatment of patients with relapsed SCLC or OC.

Carcinoma, Small Cell↗
PubMed2006

Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury.

PURPOSE: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. METHODS AND MATERIALS: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status>or=70, and life expectancy>or=6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m2) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. RESULTS: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. CONCLUSIONS: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity.

Aged↗
PubMed2006

A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer.

OBJECTIVE: To determine the feasibility and maximum tolerated dose of dose-dense topotecan as induction chemotherapy before standard therapy (carboplatin plus etoposide alone or in combination with radiotherapy) in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with SCLC and good performance status were eligible. Three 2-week cycles of dose-dense topotecan administered on days 1-3 with granulocyte colony-stimulating factor support were followed by four cycles of standard carboplatin plus etoposide therapy alone (extensive-stage SCLC) or with radiotherapy (limited-stage SCLC). The dose of topotecan was escalated from 1.5 mg/m2/day to 2.5 mg/m2/day in increments of 0.25 mg/m2/day within cohorts of 3-5 patients each. Dose-limiting toxicity was defined as any grade 3 or 4 toxicity resulting in a treatment reduction or a delay of >3 days. RESULTS: Twenty-two patients with SCLC (5 limited-stage, 17 extensive-stage) were enrolled. Treatment was well tolerated. The dose-limiting toxicities were thrombocytopenia and neutropenia, and the maximum tolerated dose of dose-dense topotecan induction therapy was 2.25 mg/m2/day. Overall, topotecan-related grade 3/4 haematological toxicities included neutropenia (n = 4), thrombocytopenia (n = 3) and febrile neutropenia (n = 1). No grade 4 non-haematological toxicities occurred. Grade 3 adverse events included nausea (n = 2), renal toxicity (n = 1) and anorexia (n = 1). Toxicity during the carboplatin plus etoposide +/- radiotherapy phase of therapy was consistent with that reported in previous trials. The overall response rate was 80% for limited-stage and 76% for extensive-stage SCLC. Median survival was 8 months in patients with limited-stage SCLC and 13.5 months for patients with extensive-stage SCLC. CONCLUSION: The results of this phase I study suggest that a regimen of sequential dose-dense topotecan and carboplatin plus etoposide is feasible, and the preliminary activity observed in patients with SCLC warrants further investigation at a starting dose of topotecan 2.25 mg/m2/day.

Anorexia↗
PubMed2005

Lack of trastuzumab activity in nonsmall cell lung carcinoma with overexpression of erb-B2: 39810: a phase II trial of Cancer and Leukemia Group B.

BACKGROUND: The overexpression of HER-2 occurs in a minority of patients with nonsmall cell lung carcinoma. Trastuzumab, which is a monoclonal antibody to HER-2, is an effective treatment in some women with breast carcinomas that overexpress HER-2, as demonstrated by immunohistochemistry. The objective of this Phase II study was to determine whether trastuzumab would effect responses in patients with nonsmall cell lung carcinoma who had tumors that overexpressed HER-2. METHODS: Patients were required to have Stage IIIB or Stage IV nonsmall cell lung carcinoma and tumors with 2+ or 3+ expression of HER-2, as determined with immunohistochemistry, and they may have received up to 1 prior chemotherapy regimen. Trastuzumab at a dose of 4 mg/kg was given intravenously on Week 1; then, weekly doses of 2 mg/kg were given. Response revaluation was performed every 8 weeks. RESULTS: Among 209 screened patients, 24 patients (11%) had tumors with 2+ or 3+ expression of HER-2. One patient achieved a partial response, and one patient experienced a treatment-related death due to pulmonary toxicity. CONCLUSIONS: Single-agent trastuzumab did not exhibit significant clinical activity against nonsmall cell lung carcinoma when HER-2 expression levels were measured by immunohistochemistry.

Adult↗
PubMed2005

A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer.

BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1-2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors.

Journal Article↗
PubMed2005

Epidermal growth factor receptor inhibitors and their role in non-small-cell lung cancer.

The epidermal growth factor receptor (EGFR) is a promising target in the treatment of advanced stage non-small-cell lung cancer (NSCLC). Currently erlotinib and gefitinib are approved by the US Food and Drug Administration, whereas cetuximab is being studied for use in NSCLC. Erlotinib has shown a survival advantage in patients with advanced NSCLC. Further studies have identified female sex, nonsmokers, Asian race, good performance status, and adenocarcinoma histology as predictors of patient response to these agents. A genetic mutation in EGFR has also been correlated with an increase in response.

Adult↗
PubMed2005

Topotecan in the treatment of elderly patients with relapsed small-cell lung cancer.

BACKGROUND: Almost 70% of all patients with lung cancer in the United States are>65 years of age, and the incidence of small-cell lung cancer (SCLC) increases with age until the eighth decade of life. However, elderly patients are underrepresented in clinical trials and are often suboptimally treated. The validity of age as a prognostic factor for toxicity or survival remains controversial. PATIENTS AND METHODS: To investigate the safety and efficacy of topotecan (an approved treatment for relapsed SCLC) in older patients, we performed a retrospective analysis in patients >or= 65 years of age versus patients < 65 years of age from 5 large topotecan trials. In all 5 trials, patients received topotecan 1.5 mg/m2 per day via a 30-minute intravenous infusion on days 1 through 5 of a 21-day cycle. Efficacy and tolerability outcomes were assessed for both age groups. RESULTS: Topotecan was similarly tolerated in both age groups, with generally manageable hematologic toxicity. The incidence, duration, and onset of severe hematologic toxicities did not vary significantly with age. In the<65 age group, grade 4 neutropenia and leukopenia were reported in 72% and 32% of patients, respectively; in the >or= 65 age group, grade 4 neutropenia and leukopenia were reported in 77% and 31% of patients, respectively. Grade 4 thrombocytopenia was less common in the<65 age group. Nonhematologic toxicities, median time to progression, and overall survival were comparable between groups. CONCLUSION: This is the first demonstration of the safety and efficacy of topotecan in older patients with recurrent SCLC. Future studies are needed to fully characterize the role of topotecan in the treatment of older patients.

Adult↗
PubMed2004

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

PURPOSE: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). METHODS: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. RESULTS: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately 80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. CONCLUSION: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.

Adult↗
PubMed2003

Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy.

PURPOSE: To report the incidence of late complications in long-term survivors of very-high-dose thoracic radiotherapy (RT) treated on a prospective clinical trial. METHODS AND MATERIALS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved lymph nodes to a dose of 73.6 Gy at 1.6 Gy twice daily. If the plasma transforming growth factor-beta1 (TGF-beta1) level was normal after 73.6 Gy, additional twice-daily RT was delivered to successively higher total doses until the maximal tolerated dose was reached. Patients within a given dose level were followed for 6 months before escalation to the next dose level was permitted. Late complications were defined according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Thirty-eight patients were enrolled between 1996 and 1999. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGF-beta1 levels. Fourteen patients received dose escalation (80 Gy in 8; 86.4 Gy in 6). Grade 3 or greater late complications occurred in 4 of 24, 1 of 8, and 2 of 6 patients treated to 73.6, 80, and 86.4 Gy, respectively. The corresponding patient numbers with late Grade 4-5 toxicity were 3 of 24, 0 of 6, and 0 of 8. Overall, 7 (18%) of the 38 patients developed Grade 3-5 late toxicity. Nonpulmonary complications predominated (4 of 7). Five (71%) of seven serious complications developed within 11 months after RT; however, the remaining two complications (29%) occurred very late (at 43 and 62 months). The 5-year actuarial risk of late Grade 3-5 complications was 33%. CONCLUSION: Long-term survivors of very-high-dose RT for non-small-cell lung cancer have a significant risk of severe treatment-related complications. At these high dose levels, the predominant toxicity may no longer be pulmonary. All Grade 4-5 complications occurred in patients whose dose was limited to 73.6 Gy because of a persistently elevated TGF-beta1. Thus, persistently elevated plasma TGF-beta1 levels toward the end of RT may identify patients at greatest risk of severe complications.

Adult↗
PubMed2003

Distress and motivation for smoking cessation among lung cancer patients' relatives who smoke.

BACKGROUND: Heightened distress at the time of a loved one's lung cancer diagnosis may motivate relatives to quit smoking or could undermine cessation. METHODS: Relatives of new lung cancer patients at Duke were surveyed by telephone to assess diagnosis-related depression, distress, and motivation for smoking cessation. RESULTS: Relatives who reported above average avoidant and intrusive thinking patterns, depressive symptoms or worry were more likely to report that the patient's diagnosis increased their intentions to quit than the less distressed. CONCLUSIONS: Interventions are needed that encourage smoking cessation as a strategy for adaptively coping with a loved ones' lung cancer diagnosis.

Adult↗
PubMed2003

Serum CYFRA 21-1 in advanced stage non-small cell lung cancer: an early measure of response.

OBJECTIVES: Our objective was to test the prognostic importance of both the pretreatment level and change in serum CYFRA 21-1 after one cycle of chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to compare these two CYFRA variables to routine clinical stage and response as measured by imaging. PATIENTS AND METHODS: Our patients consisted of 58 with advanced NSCLC who were treated with chemotherapy. Fourteen were stage IIIa, 8 stage IIIb, and 36 stage IV, and none had received previous treatment. The choice of chemotherapy was left to the discretion of the treating physicians. We collected two serum samples, one before the first cycle of chemotherapy and the second before the second cycle, and analyzed these for serum CYFRA 21-1 using an electrochemiluminescence immunoassay and the ElecSys 2010 system (Roche Diagnostics Corp., Indianapolis, IN). We expressed changes in CYFRA in terms of the natural ratio logarithm of post-treatment to pretreatment CYFRA, and we used the Cox proportional hazards model to analyze survival time. RESULTS: Patients experienced an average drop of 27% in serum CYFRA after the first cycle of chemotherapy. Furthermore, the Cox model demonstrated that both the initial natural logarithm of serum CYFRA and presence of >27% drop in CYFRA were significantly related to subsequent survival (model P < 0.0006), but neither clinical stage nor clinical response related to survival (P > 0.1). CONCLUSION: In advanced stage NSCLC, the initial level of serum CYFRA appears to provide more prognostic information than clinical stage. Furthermore, a drop of >27% in CYFRA after one cycle of therapy adds prognostic information, so that this threshold appears to be an early measure of response to chemotherapy.

Adenocarcinoma↗
PubMed2002

Perceptions of patients' self-efficacy for managing pain and lung cancer symptoms: correspondence between patients and family caregivers.

This study examined the degree of correspondence between lung cancer patients and their family caregivers in their perceptions of the patients' self-efficacy for managing pain and other symptoms of lung cancer, and the association of this correspondence to demographic, disease, and psychosocial variables. Thirty patients who were newly diagnosed with lung cancer and their primary family caregivers completed telephone interviews assessing the patient's symptoms, the patient's self-efficacy for managing symptoms, the quality of the relationship between the patient and caregiver, patient and caregiver psychological distress, and caregiver strain. Although patients and their caregivers showed a moderate degree of agreement in their perceptions of the patient's self-efficacy for managing pain and other symptoms, there was considerable variability in the degree of congruence. Factors that contributed to lower levels of congruence included low patient-rated self-efficacy, female gender of the patient, high patient psychological distress, and high caregiver strain. Caregivers were about evenly split in their tendency to overestimate versus underestimate the patient's self-efficacy. A poorer quality of relationship between the caregiver and the patient (as rated by the patient), high levels of patient-rated symptoms, and high levels of caregiver strain were associated with caregivers overestimating patient self-efficacy.

Adult↗
PubMed2002

Satisficing in hypothesis generation.

Research in hypothesis generation suggests that people might act as satisficers and be less likely to generate plausible alternative hypotheses when they already have a hypothesis that accounts for the data in hand. Three experiments simulated scientific hypothesis development. In all 3, participants who had been given a hypothesis consistent with available data generated proportionally fewer of the simplest alternative hypotheses than participants given no such satisficing hypothesis. Furthermore, participant satisficing occurred regardless of whether the provided hypothesis was generated a priori or post hoc and despite high incentives for completeness. Limitations and implications of these findings are discussed for hypothesis development and the practice of taking post hoc hypotheses suggested by one's results and presenting them as a priori hypotheses.

Humans↗