Sequential versus concurrent paclitaxel and carboplatin for the treatment of advanced non-small cell lung cancer in elderly patients and patients with poor performance status: results of two Phase II, multicenter trials.

The primary objective of these trials was to determine the 1-year survival of advanced non-small cell lung cancer (ANSCLC) patients (> or =70 years with PS 0-2 or > or =18 years with PS 2) receiving sequential paclitaxel and carboplatin (P --> C) or concurrent P + C. The secondary objectives were assessment of toxicities and quality of life. A total of 121 patients with NSCLC were treated. P--> C patients received paclitaxel (80 mg/m(2)) weekly x 3, followed by 1 week of rest; these 4-week cycles were repeated until relapse. At relapse, patients received carboplatin (AUC = 5, IV) on Day 1 of each 3-week cycle until evidence of further progression or lack of improvement. P + C patients received paclitaxel (80 mg/m(2)) and carboplatin (AUC = 2), weekly x 3, followed by 1 week of rest, until relapse. Patients in both studies were premedicated prior to paclitaxel administration. Sequential P + C resulted in a median survival of 8.2 months (range: <1-18.8) and P + C patients had a median survival of 9.2 months (range: <1-22.0). In both groups (P--> C) and P + C), the 1-year survival was 31%. For patients treated sequentially, treatment-related AEs (TRAE, > or =Grade 3) included fatigue (7%), neuropathy (5%), and leukopenia and diarrhea (3%, each). Grade 4 AEs were limited to neutropenia, febrile neutropenia, and sepsis (1 episode each). For patients receiving concurrent P + C, TRAE included neutropenia and leukopenia (15%, each) and shortness of breath and bilateral bone pain (10%, each). Leukopenia (n = 2) and neutropenia (n = 1) were the only Grade 4 events reported. The analysis of quality of life (QOL) questionnaires indicated that there were no obvious differences between treatment groups during the study. These drugs and treatment schema were well-tolerated when administered in the community setting and resulted in survival rates that were similar to what is reported in the literature with combination therapy administered to "high risk" patients. Finding the optimal chemotherapy regimen, that can be tolerated, remains a challenge in elderly patients.

A phase II multicenter study of combined topotecan and gemcitabine as first line chemotherapy for advanced non-small cell lung cancer.

UNLABELLED: This trial was designed to determine the 1-year survival rate, efficacy, and safety, produced by topotecan and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (ANSCLC). Fifty-three patients were enrolled; 51 received treatment. Topotecan 1 mg/m(2), days 1-5 and gemcitabine 1 g/m(2) days 1 and 15 were administered IV, each drug over 30 min; cycles consisted of 28 days. Treatment continued until progressive disease or intolerable toxicity. Nineteen patients (36%) had Eastern Cooperative Oncology Group criteria performance status (ECOG PS) = 0, 34 (64%) PS = 1. Median age was 64 years; 37 patients (70%) were male. HISTOLOGY: adenocarcinoma (42%), squamous cell carcinoma (28%), large cell (19%), and unclassified (11%). Among 47 evaluable patients, eight (17%) had partial response, 11 (23%) had stable disease. One-year survival was 39% and median survival was 7.6 months (range, < 1-19.6). Grade 3 and 4 toxicities included neutropenia (53%), anemia (18%), thrombocytopenia (12%), asthenia (8%), and gastrointestinal disorders (8%); three patients (6%) experienced neutropenic fever. There were no treatment-related deaths. The combination topotecan/gemcitabine produced a 1-year survival similar to previous platinum-based regimens, when used as first line chemotherapy for ANSCLC. The toxicity profile was acceptable.

Genetic, physical, and phenotypic characterization of the Del(13)Svea36H mouse.

The Del(13)Svea36H deletion was recovered from a radiation mutagenesis experiment and represents a valuable resource for investigating gene content and function at this region of mouse Chromosome (Chr) 13 and human Chr 6p21.3-23 and 6p25. In this paper we examine the physical extent of chromosome loss and construct an integrated genetic and radiation hybrid map of the deleted segment. We show that embryos which are homozygous for the deletion die at or before implantation and that heterozygotes are subviable, with a substantial proportion of carriers dying after mid-gestation but before weaning. The majority of viable carriers exhibit a variety of phenotypes including decreased size, eyes open at birth, corneal opacity, tail kinks, and craniofacial abnormalities. Both the heterozygous viability and the penetrance of the visible phenotypes vary with genetic background.

A YAC-based physical map of the mouse genome.

A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.

Breast Cancer Screening Project in Northeast Florida.

The American Cancer Society--Duval Unit, in June, 1987, helped organize a community demonstration screening project involving all hospitals and institutions with mammography units in the area. A Northeast Florida Cooperative Breast Cancer Screening Group was formed comprised of physicians and administrators from each institution. A total of 1,200 women agreed to participate in the project and each underwent complete screening including education, instruction in self-examination, physical examination by a physician and mammography as indicated according to ACS guidelines. Of the study group, 1,032 women were eligible for mammography at a participating center, and 628 (61%) underwent a mammogram at no cost to them as instructed. Twenty four (4%) had definite abnormalities which led to biopsy and seven (1%) of them had malignant lesions. The medical community organized to provide breast cancer screening and follow-up with low-cost mammography.

Dielectric measurements for the design of an electromagnetic rewarming system.

The work described in this paper is intended to provide a basis for the design of a controlled rewarming system for cryopreserved tissues and organs using electromagnetic energy. For rapid rewarming (say, greater than 10 degrees C/min), the temperature distribution in the organ is effectively determined by the uniformity (or otherwise) of the power deposition, which is in turn controlled by the electrical properties of the perfused tissue. In this contribution, we describe the measurement system we have used to characterize the electrical properties of perfusates and perfused rabbit kidney tissue from -30 to +20 degrees C. Measurements have been made on three perfusates using an open-ended coaxial probe sensor over a continuous range of radio and microwave frequencies covering 50 MHz to 2.6 GHz. Results show that the behavior of the electrical properties with increasing temperature is unfavorable at either end of the frequency range investigated--either the power absorption has a positive temperature coefficient or the penetration depth is too shallow. However, there is a compromise frequency range, determined in part by the perfusate composition, where these factors are much less serious. In this frequency range, the electrical properties of the perfused tissue are dominated by the properties of the perfusate. Modifications to the perfusate composition, e.g., reducing the concentration of electrolytes by adding sucrose, can further improve the temperature dependence of the electrical properties.

Effects of low-amplitude pulsed magnetic fields on cellular ion transport.

Pulsed magnetic fields (PMFs) are widely used to treat difficult fractures of bone and other disorders of connective tissue. It is not clear how they interact with tissue metabolism, although it has been proposed that induced currents or electric fields impinging on cell membranes may modify their ion transport function. This hypothesis was tested by treating in vitro models for ion transport processes with short-term exposure to PMFs. No change occurred in active transport of potassium or calcium in human red cells or in calcium transport through an epithelial membrane. We considered less direct action on red cell membranes, that their permeability might be modified after PMF treatment, and also that PMFs might alter the extracellular ionic activity within connective tissue by interacting with its Donnan potential. Each of these studies proved negative, and we conclude that the PMF waveforms used here do not exert a general short-term effect on cellular ion transport.

Parallel game-tree search.

The design issues affecting a parallel implementation of the alpha-beta search algorithm are discussed with emphasis on a tree decomposition scheme that is intended for use on well ordered trees. In particular, the principal variation splitting method has been implemented, and experimental results are presented which show how such refinements as progressive deepening, narrow window searching, and the use of memory tables affect the performance of multiprocessor based chess playing programs. When dealing with parallel processing systems, communication delays are perhaps the greatest source of lost time. Therefore, an implementation of our tree decomposition based algorithm is presented, one that operates with a modest amount of message passing within a network of processors. Since our system has low search overhead, the principal basis for comparison is the communication overhead, which in turn is shown to have two components.

Estrogen receptor status and response to chemotherapy in advanced breast cancer: the Tufts-Shattuck-Pondville experience.

Eighty-eight patients with advanced breast cancer were retrospectively reviewed to compare estrogen receptor (ER) data with response to cytotoxic chemotherapy. All assays were done in a single laboratory. All patients were cared for at a single institution. Thirty-four patients were treated with chemotherapy, 30 of whom were evaluable for response by criteria of the Eastern Cooperative Oncology Group (ECOG). Of 16 ER-positive patients, 12 (75%) responded; of 14 ER-negative patients, six (43%) responded (P < 0.05). The two groups did not differ significantly in chemotherapy received, menopausal status, site of predominant disease, stage at diagnosis, or disease-free interval. Response to cytotoxic chemotherapy does not appear to correlate with ER status.