Differences in nativity, age and gender may impact health behavior and perspectives among Asian Indians.

OBJECTIVE: Identify health perspectives among Asian Indians in greater Houston area, to guide a tailored community wide survey. DESIGN: Four focus groups of different ages, gender, and nativity were conducted at which participants were asked for their opinions about specific health topics. Key informant interviews were conducted with ten community leaders to validate focus group responses. Recordings from focus groups and key informant interviews were transcribed and analyzed. RESULTS: Diabetes, cancer, and hypertension were primary health concerns. Common themes were sedentary lifestyle and poor health literacy. Older participants were more accepting of having familial hypertension and high cholesterol. Women were more concerned about health of family members and dietary habits. Perspectives differed on eating habits, physical activity, use of Western medicine, and smoking based on nativity. Responses from key informant interviews validated focus group findings. CONCLUSION: Perspectives on health may differ among Asian Indians depending on gender, age, and nativity.

Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial.

PURPOSE: The addition of cytokines to chemotherapy has produced encouraging results in advanced melanoma. In this phase III trial, we compared the effects of chemotherapy (cisplatin, vinblastine, and dacarbazine [CVD]) with those of sequential biochemotherapy consisting of CVD plus interleukin-2 and interferon alfa-2b. PATIENTS AND METHODS: Metastatic melanoma patients who had not previously received chemotherapy were stratified by prognostic factors and given chemotherapy or biochemotherapy. CVD consisted of dacarbazine (days 1 and 22) and cisplatin and vinblastine (days 1 to 4 and 22 to 25). Biochemotherapy involved CVD with vinblastine reduced 25% plus interleukin-2 by 24-hour continuous infusion (on days 5 to 8, 17 to 20, and 26 to 29) and interferon alfa-2b by subcutaneous injection (on days 5 to 9, 17 to 21, and 26 to 30). Response was assessed every 6 weeks. RESULTS: Among 190 patients enrolled, 91 were assessable for biochemotherapy and 92 for chemotherapy. Ten percent of the patients were alive a median of 52 months from start of therapy. Response rates were 48% for biochemotherapy and 25% for chemotherapy (P =.001); six patients given biochemotherapy and two given chemotherapy had complete responses. Median time to progression (TTP) was 4.9 months for biochemotherapy and 2.4 months for chemotherapy (P =.008); median survival was 11.9 and 9.2 months, respectively (P =.06). The influence of treatment on TTP and survival was confirmed in multivariate analyses with other prognostic factors not included in the original stratification. Biochemotherapy produced substantially more constitutional, hemodynamic, and myelosuppressive toxic effects. CONCLUSION: Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.

Phase II study of thalidomide in patients with metastatic melanoma.

The aim of this study was to determine the antitumour activity and toxicity of thalidomide in patients with metastatic melanoma. Between July 1999 and July 2001, 20 patients with metastatic melanoma were enrolled into this study. Patients were required to have progressive disease following standard therapies (unless there was a known contraindication for their usage) and to be free from symptomatic brain metastases. Thalidomide was administered orally at a starting dose of 200 mg/day, with increments of 100 mg every 7 days to a maximum dose of 800 mg/day. Patients experiencing intolerable side effects had their dose reduced to the maximum tolerated dose. Response and tolerance to treatment were assessed at 4 week intervals and therapy was continued until progression of disease or development of intolerable side effects despite appropriate dose reduction. All 20 patients were assessable for response. No objective response (complete or partial remission) was observed. In seven patients (35%), stable disease with a duration of 12-32 weeks (median 16 weeks) was seen. The median time to progression for all patients was 8 weeks (range 5-32 weeks) and the median overall survival was 20 weeks (range 7-130+ weeks). Treatment was generally well tolerated. Nine patients (45%) were able to tolerate the maximal planned dose of thalidomide (800 mg/day). Constipation, fatigue, somnolence and dryness of skin or mouth were the most common side effects. Thalidomide appears to possess cytostatic activity in patients with metastatic melanoma. Further studies of thalidomide in melanoma are warranted.

A randomized phase III trial of biochemotherapy versus interferon-alpha-2b for adjuvant therapy in patients at high risk for melanoma recurrence.

The objective of this study was to compare the clinical benefit of biochemotherapy and interferon-alpha-2b (IFN) as adjuvant therapy. Biochemotherapy has higher response rates than other regimens in patients with metastatic melanoma. We conducted a randomized phase III study comparing the clinical benefit of biochemotherapy and IFN as adjuvant therapy. Patients who had undergone lymphadenectomy for melanoma metastatic to regional lymph nodes were randomly assigned to either biochemotherapy or IFN, and IFN patients were further randomized to either high-dose IFN (HDI) or intermediate-dose IFN (IDI). The primary end point was relapse-free survival (RFS); the secondary end point was overall survival (OS). The planned enrollment was 200 patients, the number required to have 80% power to detect, at a significance level of 5%, an improvement in median RFS from 18 to 36 months and an improvement in median OS from 40 to 80 months between the IFN and biochemotherapy groups. A futility analysis was performed because of slow accrual. One hundred and thirty-eight patients were enrolled - 71 in the biochemotherapy group, 34 in the HDI subgroup, and 33 in the IDI subgroup. No significant differences in median RFS or OS between the HDI and IDI subgroups were observed. With a median follow-up of 49.3 months, neither the biochemotherapy nor IFN group had reached median RFS or OS, and there were no significant differences in estimated median RFS or OS (P=0.86 and 0.45, respectively) between the two groups. Biochemotherapy is not more effective than IFN as adjuvant therapy for melanoma. These findings support early termination of this trial.

A phase II open-label trial of apomine (SR-45023A) in patients with refractory melanoma.

Metastatic melanoma continues to be a very difficult disease to treat. Options are limited and often have very little impact on the course of the disease. The objective of the current study was to evaluate the efficacy and safety of continuously administered Apomine (SR-45023A), a novel bisphosphonate, in patients with previously treated metastatic malignant melanoma. Adult patients with previously treated metastatic melanoma received Apomine 100 mg orally, twice daily (total dose 200 mg per day) continuously for 28 days (defined as a cycle). Treatment was continued until disease progression or unacceptable toxicity. A total of 42 patients received at least one dose of Apomine. Stable disease was achieved in 2 patients (5%). No complete or partial responses were observed. Progression free survival of at least 16 weeks was observed in 6 patients (14%). The median overall survival was 6.1 months (95% CI, 4.9-9.4 months). Time to treatment failure was 1.7 months (95% CI, 1.6-1.8 months) with Apomine therapy. By cycle 2, Apomine concentrations reached steady-state. Apomine was well tolerated with only 37% of patients experiencing any drug-related event. Abdominal pain was the most frequent adverse event occurring in 26% of patients. In conclusion, Apomine, at the current dose studied, failed to produce a 30% progression free survival rate at 16 weeks considered to be a meaningful benefit for further development.

Phase I trial of subcutaneous recombinant human interleukin-2 in patients with metastatic melanoma.

BACKGROUND: Interleukin-2 (IL-2) has activity in metastatic melanoma when given in high doses by the intravenous (IV) route, but its side effects and effectiveness when given in intermediate to high doses by the subcutaneous (SC) route have not been studied adequately. This study sought to determine the maximum tolerated dose (MTD) of IL-2 administered once daily by the SC route. METHODS: Outpatients with progressive metastatic melanoma after chemotherapy were enrolled in a Phase I trial of IL-2 administered SC daily for 5 days per week for 4 consecutive weeks, repeated at 6-week intervals. Patients were instructed to drink at least 2 L of fluid daily. IL-2 pharmacokinetic studies were performed at the two highest dose levels. Toxicity was recorded weekly using the National Cancer Institute Common Toxicity Criteria. Response was assessed at 6-week intervals. RESULTS: Three patients, 6 patients, 6 patients, and 4 patients received a median of 2 courses of SC IL-2 at dose levels of 6 MIU/m(2), 9 MIU/m(2), 12 MIU/m(2), and 15 MIU/m(2), respectively. Failure to maintain adequate fluid intake was responsible for 2 episodes of syncope at the 9 MIU/m(2) dose level and for 2 incidents of reversible prerenal azotemia at the 15 MIU/m(2) dose level. IL-2 treatment was resumed in these patients without incident. At the 15 MIU/m(2) dose level, 2 patients had severe headaches, depression, and visual hallucinations requiring discontinuation of treatment. Cough and fluid retention at the end of the third and fourth weeks at the 15 MIU/m(2) dose level approximated the symptoms reported by inpatients treated by continuous IV infusion at 9 MIU/m(2) on the same schedule. There was a partial response and a complete response in subcutaneous disease at the 12 MIU/m(2) and 15 MIU/m(2) dose levels, respectively, each lasting < 2 months. Plasma IL-2 levels after SC injection of 1000-5000 pg/mL reached maximum by 3 hours and were detectable for up to 48 hours after administration. The half-lives for SC IL-2 absorbance and clearance were 1.6 hours and 5.2 hours, respectively, and the calculated area under the curve was 30,584 pg/mL x hour. CONCLUSIONS: SC IL-2 was well tolerated and had high sustained bioavailability at the higher doses studied. The MTD for a daily SC regimen was 12 MIU/m(2) and is recommended for future studies.