Complexities of holistic community-based participatory research for a low income, multi-ethnic population exposed to multiple built-environment stressors in Worcester, Massachusetts.

Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of Worcester, Massachusetts are exposed to cumulative, chronic built-environment stressors, and have limited capacity to respond, magnifying their vulnerability to adverse health outcomes. "Neighborhood STRENGTH", our community-based participatory research (CBPR) project, comprised four partners: a youth center; an environmental non-profit; a community-based health center; and a university. Unlike most CBPR projects that are single topic-focused, our 'holistic', systems-based project targeted five priorities. The three research-focused/action-oriented components were: (1) participatory monitoring of indoor and outdoor pollution; (2) learning about health needs and concerns of residents through community-based listening sessions; (3) engaging in collaborative survey work, including a household vulnerability survey and an asthma prevalence survey for schoolchildren. The two action-focused/research-informed components were: (4) tackling persistent street trash and illegal dumping strategically; and (5) educating and empowering youth to promote environmental justice. We used a coupled CBPR-capacity building approach to design, vulnerability theory to frame, and mixed methods: quantitative environmental testing and qualitative surveys. Process and outcomes yielded important lessons: vulnerability theory helps frame issues holistically; having several topic-based projects yielded useful information, but was hard to manage and articulate to the public; access to, and engagement with, the target population was very difficult and would have benefited greatly from having representative residents who were paid at the partners' table. Engagement with residents and conflict burden varied highly across components. Notwithstanding, we built enabling capacity, strengthened our understanding of vulnerability, and are able to share valuable experiential knowledge.

Phase I/II study of 19-nor-1alpha-25-dihydroxyvitamin D2 (paricalcitol) in advanced, androgen-insensitive prostate cancer.

PURPOSE: We assessed the safety and efficacy of the vitamin D analogue, 19-nor-1alpha-25-dihydroxyvitamin D2 (paricalcitol), in patients with androgen-independent prostate cancer. EXPERIMENTAL DESIGN: Patients received paricalcitol i.v. three times per week on an escalating dose of 5 to 25 microg (3-15 microg/m2). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were characterization of toxicity in this population, changes in serum parathyroid hormone (PTH), and survival. RESULTS: A total of 18 patients were enrolled. No patient showed a sustained 50% drop in serum PSA, despite several large declines in PSA (e.g., 1,300 ng/mL). Paricalcitol was well tolerated. One instance of significant hypercalcemia, a serum calcium of 14.3 mg/dL, was observed at the highest dose (25 microg). At entry into the study, seven (41%) of the patients had elevated serum levels of PTH, which were significantly reduced by paricalcitol. Higher levels of serum PTH at study entry were significantly and negatively associated with survival (P<0.01). CONCLUSION: No objective responses were seen in the primary end point. However, elevated serum levels of PTH, a common feature of advanced prostate cancer, were reduced by paricalcitol. Because elevated PTH is associated with increased cardiovascular and skeletal morbidity, including an increased risk for pathologic fracture, further evaluation of paricalcitol in the reduction of skeletal morbidity in advanced prostate cancer is warranted.

Phase II trial of combination interferon-alpha and thalidomide as first-line therapy in metastatic renal cell carcinoma.

OBJECTIVES: To present the results of a Phase II trial of thalidomide and interferon-alpha in renal cell carcinoma. METHODS: Patients with metastatic clear cell renal cell carcinoma and no prior systemic therapy were accrued. Interferon-alpha was administered at 5 million units subcutaneously three times per week. Thalidomide was started at 100 mg/day for 2 weeks and then escalated 200 mg every 2 weeks to 1000 mg or until grade 3-4 toxicity developed. Patients were assessed radiographically at baseline and after 12 weeks. Steady-state thalidomide plasma concentrations were determined. RESULTS: Thirty patients were enrolled. The median age was 62 years. Seventeen patients (57%) had undergone nephrectomy before therapy. One patient died during therapy. Of the 30 patients, 29 had at least grade 2 toxicity and 17 patients had at least grade 3. At 12 weeks, no patient had a complete response, 2 had a partial response (6.7%), 8 had stable disease (26.7%), and 11 (including 1 patient with an initial partial response) had disease progression (36.7%). Nine patients were removed from the study before 12 weeks. The median follow-up was 49.6 weeks (range 2.4 to 123.7). The median time of participation in the study was 11.1 weeks (range 1.4 to 63.9). At last follow-up, 2 patients were receiving the study therapy, 1 with stable disease at 64 weeks and 1 with a partial response at 53 weeks. The median survival was 68 weeks. A linear relationship was found between the thalidomide plasma concentration and dose. No relationship was apparent between the concentration and either treatment-related toxicity or response. CONCLUSIONS: Interferon-alpha and thalidomide as front-line therapy for metastatic renal cell carcinoma showed limited activity. The objective response rate was 7%. One third of patients experienced toxicity that required discontinuation of thalidomide. Randomized controlled studies are needed to determine any objective benefit of this regimen over either drug alone.

Irinotecan/gemcitabine followed by twice-weekly gemcitabine/radiation in locally advanced pancreatic cancer.

Early clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect. This multi-institution phase II trial of induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation has been initiated to determine the activity of this regimen in patients with unresectable pancreatic cancer. Patients received two cycles of induction irinotecan (100 mg/ m2 IV) and gemcitabine (1,000 mg/m2 IV) on days 1 and 8 of each 3-week cycle. Following the induction therapy, patients without disease progression received twice-weekly gemcitabine at 40 mg/m2 and radiation. Nine patients have been enrolled in the study to date. Median patient age was 71 years (range: 65-85 years). The major toxicity observed thus far was grade 3/4 neutropenia. Grade 3/4 nonhematologic toxicity was rarely observed and included dehydration (12%) and diarrhea (12%), which were likely related to the irinotecan. No treatment-related deaths have occurred. These preliminary data suggest that this regimen is well tolerated. Although the data are limited, tumor progression during the induction chemotherapy has not been observed thus far (radiographically or biochemically [CA-19-9]).

Bladder cancer.

Bladder cancer is a common and chemotherapy-responsive tumor, related to tobacco smoking, environmental arsenic exposure, industrial dye exposure, and parasitic schistosomiasis exposure. Both reduction of carcinogen exposure and chemoprevention, possibly with cyclooxygenase 2 inhibitors, should reduce the incidence. The search for the ideal screening and monitoring test continues with some promising new candidates, including survivin. Although 10-year survival can be achieved in 87% of early-stage patients with muscle-invasive disease rendered T(0) and 57% of those rendered T(1) at second look after transurethral resection bladder tumor, most still require radical cystectomy. Continued improvements in surgical techniques permit gains in quality of life after the procedure. Ten-year survival can still be achieved with cystectomy in the face of grossly positive lymph nodes in 32% of T(2) and 10% of T(3) patients. A recent meta-analysis indicates that preoperative irradiation is unlikely to be beneficial, but definitive chemoradiation can produce significant 5-year survival rates in nonoperative candidates and those desiring bladder preservation. The Intergroup now has preliminary data from a Southwest Oncology Group-based trial showing a significant benefit for neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin. The regimen of gemcitabine and cisplatin is equally efficacious with less toxicity than methotrexate, vinblastine, doxorubicin, and cisplatin. It has been adopted as the standard arm in a phase III trial for advanced bladder cancer, comparing it with the triplet of gemcitabine, paclitaxel, and cisplatin. Other active agents in bladder cancer include ifosfamide, carboplatin, docetaxel, and vinorelbine, and various doublets of these agents are being tested in phase II trials, with promising results.