7546 Background: Metastatic melanoma responds poorly to currently available therapies, many of which require hospitalization. de Gast reported that chemobiotherapy with TMZ, GM-CSF, IL-2, and IFN in patients with melanoma has efficacy with toxicity that is manageable on an outpatient basis (de Gast et al Br J CA 88:175–80, 2003). Methods: A multi-centre open-label, Phase II trial of chemobiotherapy in patients with metastatic melanoma has been completed. The treatment regimen consisted of a 28-day cycle in which patients received oral TMZ, 150 or 200 mg/m2 on days 1 - 5, followed by daily outpatient biotherapy on days 6 - 17 with GM-CSF, 125 μg/m2 subcutaneously (SQ), IFN, 5 million units (MU) SQ and IL-2, 4 million international units/ m2 (MIU) SQ. After completion of the biotherapy cycle, patients had an 11-day rest period. The 28-day cycle was repeated as tolerated and clinically indicated. Dose adjustments were made for toxicity depending on the suspected drug interaction. Results: Thirty-one patients (23M, 8F, median age 58) were enrolled in the trial. Of these, 28 (90%) had M1c disease and over half (58%) had 3 or more sites of metastasis. Responses include 4 CR (13%), 4 PR (13%), 7 SD/MR (23%), and 16 PD (52%). The overall objective response rate was 26% (95% confidence interval 12% to 45%); all but 1 of the responding patients had M1c disease. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. The overall survival rate was 52% at 12 months and 25% at 24 months. Five patients (16%) remain alive; 2 patients have no evidence of disease at 34.7 and 25.8 months and 3 patients are alive with disease at 35.3, 28.2, and 23 months. A total of 112 28-day cycles of therapy were administered. Toxicity occurred in 78% of the cycles but was Grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles (thrombocytopenia in 2% and psychosis in 1%). Conclusion: This low-dose chemobiotherapy combination has activity in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron Chiron Chiron

Purpose The objective of this study was to further investigate the efficacy and safety of low-dose outpatient chemobiotherapy in patients with unresectable metastatic melanoma. Patients and Methods Thirty-one patients with histologically confirmed unresectable measurable metastatic melanoma were enrolled onto an open-label, multicenter phase II study. The treatment regimen consisted of oral temozolomide followed by subcutaneous biotherapy with granulocyte macrophage colony-stimulating factor, interferon-alfa, and recombinant interleukin-2 (rIL-2). Results Twenty-eight patients (90%) had M1c disease, and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and 7 (23%) of 30 experienced CNS progression after receiving chemobiotherapy. A total of 112 cycles of therapy were administered. Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles. Conclusion This low-dose chemobiotherapy combination produces clinical responses in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. It offers a reasonable alternative to high-dose regimens, such as high-dose biochemotherapy or rIL-2 requiring prolonged periods of hospitalization, or single agent outpatient regimens, such as dacarbazine, which is usually not effective in patients with M1c disease. Furthermore, it may protect against the development of brain metastases.

This research, conducted in an interdisciplinary approach and employing current education paradigms, models of learning theory, technology acceptance and attitude/technology interaction, investigated the manner in which students' learning styles affected their attitudes towards computer technology and the impact of those learning styles and attitudes on learning outcomes. Analyses of data collected from four higher education institutions over a period of two-and-a-half years using a learning style inventory based on Gregorc's Style Delineator and a computer attitude scale adapted from Loyd and Gressard's Computer Attitude Scale indicate that a student's learning style (how information is gathered from the environment and how that information is processed and organized mentally) and attitudes toward computers may be, to some extent, a factor of gender and other conditions outside the student's control (e.g., fetal brain exposure to gonadal hormones). Certain technology-favoring learning styles were found more often in males while technology-averse learning styles were found more often in females. There were positive differences between overall GPA and students' GPA in computer-focused coursework (computer GPA exceeded overall GPA) in specific learning style groupings. Data also indicate that students tended to select academic majors and instruction delivery methods that complemented their learning styles and computer attitudes. Implications for the future implementation of computers in schools and technology training, especially for females, are discussed and suggestions for future research are proposed.

Objectives: Biochemotherapy outcomes were examined in stage IV melanoma patients with previously treated or active central nervous system (CNS) metastases prior to systemic therapy. Patients and Methods: Patients who received biochemotherapy for metastatic melanoma with active or pretreated CNS metastases were compared to patients without evidence of CNS metastases in terms of response, time to progression (TTP), overall survival (OS), and treatment toxicity. Results: Twenty-six (16%) of 159 total patients began biochemotherapy with previously treated or active CNS metastases (group I), compared to 133 (84%) who were radiographically free of CNS involvement (group II). A partial or complete response to biochemotherapy was seen in 13 (50%) group I patients, compared to 56 (42%) group II patients (p = 0.243). The median TTP and median survival were 5.5 and 7.0 months, respectively, for group I patients and 6.0 and 9.9 months, respectively, for group II patients (p = 0.222 and 0.434 for TTP and OS, respectively). Five (19%) group I patients survived longer than 24 months. Gamma Knife radiosurgery or surgical resection of CNS disease prior to biochemotherapy improved survival versus delayed treatment (p = 0.017 and 0.005, respectively). Conclusion: Patients with limited CNS metastases and widespread systemic disease can achieve prolonged survival with targeted treatment of CNS lesions and aggressive systemic therapy.

University students' attitudes toward computers were assessed as a function of learning style. Analyses of responses provided by 232 students to a learning style assessment instrument and a computer attitude survey revealed that specific learning styles were associated with an affinity for (liking of), confidence in, and anxiety about the use of computers. Within those learning styles, gender differences were discovered when students manifested a clearly dominant style. The findings indicate that computer-based or computer-assisted instruction may not be appropriate for all students and that curriculum modifications to account for learning style differences may increase the effectiveness of and reduce the aversion to computers in the classroom. Additional research into the relationship between learning styles and computer attitudes may also provide assistance relative to increasing the enrollment of females in technology-oriented courses of study.

Purpose: A prospective Phase II study of a novel maintenance biotherapy regimen after induction biochemotherapy was conducted in patients with metastatic melanoma in efforts to maintain responses and improve survival.Experimental Design: Thirty-three patients with poor prognosis metastatic melanoma who achieved a partial response (PR) or stable disease (SD) to induction concurrent biochemotherapy were treated with chronic low-dose interleukin (IL)-2 and granulocyte macrophage-colony stimulating factor, and intermittent pulses of intermediate/high-dose decrescendo IL-2 over a 12-month period. The outcome of these patients was compared with a control group of patients at our institution who were treated recently with induction biochemotherapy and achieved a PR or SD.Results: Five patients (15%) achieved a complete response, and 4 patients (12%) maintained SD for at least 6 months on maintenance biotherapy. The median progression-free survival (PFS) and overall survival (OS) were 8.1 months and 18.5 months, respectively, compared with historical controls, which were PFS 5.9 months (P = 0.0015) and OS 9.3 months (P = 0.0004). Administration of maintenance biotherapy was a significant predictor of PFS (P = 0.0008) and OS (P 0.0001) in multivariate and matched-pair analyses (P = 0.002). The maintenance biotherapy regimen was well tolerated with no dose-limiting acute or cumulative toxicities.Conclusion: In this single institution study, maintenance biotherapy with IL-2 and granulocyte macrophage colony-stimulating factor in patients achieving PR or SD to induction biochemotherapy improved PFS and OS compared with historical controls. A larger multicenter Phase II trial has been initiated in an effort to confirm these results.