Outcomes Associated with Brain Metastases in a Three-Arm Phase III Trial of Gemcitabine-Containing Regimens Versus Paclitaxel Plus Carboplatin for Advanced Non-small Cell Lung Cancer

BACKGROUND: Brain metastases (BMs) are a common complication of non-small cell lung cancer (NSCLC). Because of historical data indicating a poor prognosis for patients with BM, few randomized phase III studies of advanced NSCLC have included patients with BM at presentation. Because the potential benefits of systemic therapy in patients with BM are uncertain, we analyzed data from a recent phase III study. METHODS: One thousand one hundred thirty-five chemonaïve patients with stage IIIB/IV NSCLC were randomized to receive gemcitabine/carboplatin, gemcitabine/paclitaxel, or paclitaxel/carboplatin. Stratification was based on presence or absence of BM, stage, and baseline weight loss. Patients with BM were required to be clinically stable after treatment with radiotherapy or surgery before entry. Results were retrospectively analyzed by presence or absence of BM at study entry. RESULTS: Rate of BM was 17.1% overall. The response rate was 28.9% for patients with BM (n = 194) versus 29.1% without BM (n = 941). Time to progression was 4.3 months with BM and 4.6 months without BM (p = 0.03). Median survival was 7.7 months (95% confidence interval: 6.7-9.3) among patients with BM (n = 194) and 8.6 months (95% confidence interval: 7.9-9.5) for patients without BM (n = 941), p = 0.09. Rates of hematologic adverse events were not different among patients with and without BM. CONCLUSIONS: There were no significant differences in response, survival, or hematologic toxicity for patients with or without BM; however, patients with BM had a small but significantly shorter time to progression. Nonprogressing patients with treated BM are appropriate candidates for systemic therapy and entry into clinical trials

Pemetrexed in Relapsed Small-Cell Lung Cancer and the Impact of Shortened Vitamin Supplementation Lead-In Time: Results of a Phase II Trial

INTRODUCTION: We undertook a phase II trial to assess the efficacy and safety of single-agent pemetrexed (P) in relapsed small-cell lung cancer (SCLC) patients. METHODS: Patients had limited- or extensive-stage SCLC, performance status 0 to 2, and one prior chemotherapy regimen. Initial P dose was 500 mg/m every 21 days. Planned sample sizes were 36 sensitive (S) patients in a two-stage sequential fashion with early stopping rule, and 25 refractory (R) patients in a single-stage design without stopping rule. Patients received folic acid and Vitamin B12 prior to P, and B12 could be given up until P treatment. Primary outcome measure was response rate. RESULTS: Enrollment occurred from July 2004 to March 2006. The stopping rule was invoked when <3 of 14 S patients responded. The protocol was amended to evaluate P 900 mg/m in cohorts of 40 S and 40 R patients. Overall, 121 patients were enrolled, with 116 patients treated. S (n = 53) and R (n = 63) patients were analyzed separately at both dose levels. Across the 4 treatment groups (S500, S900, R500, R900), 1 patient (2.63%) in the S900 group had a partial response. Overall, 18 patients (16%) had stable disease. Eighty-seven patients (75%) had progressive disease. Responses were not evaluable in 10 patients (8.6%). Overall response rate was 0.9%. Across treatment groups, disease control rates (partial response + stable disease) were 20%, 15.8%, 21.7%, and 12.5%, respectively. Median time to progression ranged from 1.2 to 1.5 months, median survival times ranged from 2.5 to 6.1 months, and 1-year survival rates ranged from 5.6 to 25.8%. Common grade 3/4 hematologic toxicities (at 500 and 900 mg/m) were neutropenia (16%; 9%) and leukopenia (11%; 8%), and nonhematologic toxicities were dyspnea (11%; 10%) and fatigue (16%; 9%). Retrospective analysis of cycle 1 events by timing of B12 administration showed no trend toward more frequent serious toxicities when B12 was given <7 days prior to P. CONCLUSIONS: Single-agent P 500 mg/m shows minimal activity in relapsed SCLC patients. P can be given at 900 mg/m without significant increase in serious toxicities, but does not seem to increase efficacy. B12 given <7 days before P does not seem to be associated with increased serious toxicities

A Comparison of White and African American Outcomes from a Three-Arm, Randomized, Phase III Multicenter Trial of Advanced or Metastatic Non-small Cell Lung Cancer

PURPOSE: To investigate the effect of race on the efficacy and safety of standard chemotherapy doublet regimens in African American patients, we conducted a subgroup analysis of a phase III randomized trial. PATIENTS AND METHODS: Chemonaïve patients with a performance status of 0 or 1 and stage IIIB or IV non-small cell lung cancer were randomized to arm A: gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin area under the curve 5.5 on day 1; arm B: the same schedule of gemcitabine plus paclitaxel 200 mg/m2 on day 1; or arm C: paclitaxel 225 mg/m2 on day 1 plus carboplatin area under the curve 6.0 on day 1. Cycles were repeated every 21 days up to 6. A site selection tool identified institutions with potential to recruit a minority population. Outcome and toxicity data of white and African American patients were compared. RESULTS: Of 1135 total patients, 972 were white (85.6%) and 138 were African American (12.2%). Median survival was 8.3 months for white patients (95% confidence interval [CI]: 7.7-9.3) and 9.1 months for African American patients (95% CI: 8.2-11.1). Response rates were 29.1 and 29.0%, respectively. Rates of grade 3 or 4 toxicities were comparable. Among African Americans, median survival was 7.2 months (95% CI: 5.1-10.1) for gemcitabine-carboplatin (n = 47), 10.5 months (95% CI: 7.1-15.4) for gemcitabine-paclitaxel (n = 42), and 10.2 months (95% CI: 8.5-13.2) for paclitaxel-carboplatin (n = 49). CONCLUSION: Whites and African Americans had similar outcomes, although there was some variability in survival among African Americans across the three treatment groups

Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

IntroductionPemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.MethodsThe phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.ResultsMaximum tolerated dose was gemcitabine 1500 mg/m2, followed by pemetrexed 500 mg/m2. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).ConclusionsTwice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Fluorophores-Assisted Excitation Emission Matrix Fluorescence Method for the Origin Traceability of Lily

In this work, a fluorophores-assisted excitation/emission matrix (EEM) fluorescence method was proposed to trace the origin of lily in the Chinese market. There are few active components in lilies that have fluorescent signals, and too few characteristic variables may lead to unsatisfactory accuracy in the subsequent classification. Therefore, three fluorophores, 2-Aminoethyl diphenylborinate (DPBA), o-Phthalaldehyde (OPA) and Rhodamine B (RB), were used to enrich the information of the fluorescent fingerprint of lily, which can improve the classification accuracy. The lily samples were characterized by using EEM fluorescence coupled with the alternating trilinear decomposition (ATLD) algorithm, which was able to extract information of various fluorophores in lily samples. Two chemical pattern recognition methods, principal component analysis-linear discriminant analysis (PCA-LDA) and partial least squares-discrimination analysis (PLS-DA), were used to model and trace the origin of different lilies. When the fluorophores were added, the accuracy of the test set and prediction set obtained by the classification model increased from 71.4% to 92.9% and 66.7% to 100%, respectively. The proposed method combined fluorophores-assisted EEM fluorescence with multi-way chemometric methods to extract comprehensive information on the samples, which provided a potential method for the origin traceability of traditional Chinese medicine

Gamma-delta (γδ) T-cell lymphoma – another case unclassifiable by World Health Organization classification: a case report

Abstract Background We present a case of gamma-delta T-cell lymphoma that does not fit the current World Health Organization classifications. Case presentation A 74-year-old Caribbean-American woman presented with lymphocytosis, pruritus, and non-drenching night sweats. Bone marrow and peripheral blood analyses both confirmed the diagnosis of gamma-delta T-cell lymphoma. An axillary lymph node biopsy was negative for lymphoma. Clinically absent hepatosplenomegaly and skin lesions with biopsy-proven gamma-delta T-cell lymphoma suggest that she is unclassifiable within the current classification system. Conclusions We believe this is a case of not otherwise specified gamma-delta T-cell lymphoma. Accumulation of these rare not otherwise specified cases will be important for future classification which further defines the biology of this disease

Similar distribution of simple sequence repeats in diverse completed Human Immunodeficiency Virus Type 1 genomes

AbstractThe survey of simple sequence repeats (SSRs) has been extensively made in eukaryotes and prokaryotes. However, its still rare in viruses. Thus, we undertook a survey of SSRs in Human Immunodeficiency Virus Type 1 (HIV-1) which is an excellent system to study evolution and roles of SSRs in viruses. Distribution of SSRs was examined in 81 completed HIV-1 genome sequences which come from 34 different countries or districts over 6 continents. In these surveyed sequences, although relative abundance and relative density exhibit very high similarity, some of these sequences show different preference for most common SSRs and longest SSRs. Our results suggest proportion of various repeat types might be related to genome stability