Sunitinib in patients with imatinib‑resistant gastrointestinal stromal tumor: A single center experience.

AIM: The outcome of patients with advanced gastrointestinal stromal tumor (GIST) has improved with the use of imatinib. Despite high response rates with this drug resistance eventually develops in nearly all patients. We present an analysis of prospectively collected data on sunitinib efficacy and safety in patients with imatinib‑resistant GIST. SUBJECTS AND METHODS: Between November 2006 and October 2007, patients with GIST were accrued in an approved sunitinib patient access protocol. Key eligibility criteria included tumor resistance to imatinib and/or patient intolerance to this drug. Patients received sunitinib at a starting dose of 50 mg once daily for 4 weeks in a 6 week cycle, with standardized dose modification titrated to toxicity. Patients were continued on sunitinib until disease progression or unacceptable toxicity. The endpoints were safety, overall survival (OS) and objective response rate (ORR). RESULTS: Fifteen patients, all of whom had imatinib resistance and none intolerance, with median age of 48 (26–69) years, were treated on the protocol. The most common sites of primary disease were small intestine (40%), stomach (26.7%) and retroperitoneal (26.7%). A median of 10 (1–47) cycles of sunitinib were delivered, 9 (60%) patients required dose reductions due to toxicity whereas dose delay of > 2 weeks was required in only one (6.7%) patient. There were no toxicity‑related drug discontinuations. Hypothyroidism (n = 4; 26.7%) and hand‑foot syndrome (n = 3; 20%) were the most common toxicities. There were no complete and 4 (26.7%) partial responses while prolonged disease stability was seen in 8 (53.3%) patients. At a median follow‑up of 81 months in surviving patients, the median progression‑free and overall survivals were 15.5 and 18.7 months, respectively. CONCLUSIONS: Sunitinib appears to be an effective and well‑tolerated treatment for Indian patients with imatinib‑resistant GIST with outcomes similar to that reported previously. Adverse effects can be reasonably well managed using a dose modification strategy.

Detection of dengue virus 4 from central India.

Background & objectives: Dengue is an important arboviral disease. All four dengue virus serotypes are reported to be circulating in India. It is also known that different serotypes, genotypes and clades of genotype determine outbreak severity. Dengue affected children are known to have serious disease outcome. We carried out this study to give reliable diagnosis of dengue infection in children and to detect circulating serotype in central India. Methods: Samples collected from paediatric patients suspected to have dengue fever were subjected to IgM and IgG ELISA to determine dengue virus infection. Samples collected within 0-5 days of onset of illness and positive by IgM ELISA were tested by nested reverse transcription polymerase chain reaction (nRT-PCR). The PCR products were sequenced and analyzed. Results: Of the 89 samples tested, 18 and 7 were positive for dengue IgM and IgG, respectively. Dengue activity was observed in both Jabalpur city and adjoining rural settings. One sample found positive by nRT-PCR was further sequenced to confirm dengue virus 4 as aetiological agent. Interpretation & conclusions: Our findings demonstrated dengue virus infection in children and adolescent in central India. Because of continuous changing epidemiology, it is important to monitor dengue virus activity at both serological and molecular level in this part of the country for better patient care and management.

Rate of hospitalization and inpatient care costs for HIV-1-infected patients in Pune, India.

BACKGROUND: The transition of human immunodeficiency virus (HIV) infection to acquired immune deficiency syndrome (AIDS) has begun in India, and an increase in AIDS-related hospitalizations and deaths is an anticipated challenge. We estimated the rates of hospitalization and inpatient care costs for HIV-1-infected patients. METHODS: Data were analysed on 381 HIV-1-infected persons enrolled in a HIV-1 discordant couples' cohort between September 2002 and March 2004. Inpatient care costs were extracted from select hospitals where the study patients were hospitalized and the average cost per hospitalization was calculated. RESULTS: A majority of the patients were in an advanced state of HIV-1 disease with the median CD4 counts being 207 cells/cmm (range: 4-1131 cells/cmm). In all, 63 participants who did not receive antiretroviral therapy required hospitalization, 53 due to HIV-1-related illnesses and the remaining 10 due to worsening of pre-existing conditions. The overall HIV-1-related hospitalization rate was 34.2 per 100 person-years (95% CI: 26.94-42.93). The median duration of HIV-1-related hospitalization was 10 days (range 2-48 days) and the median cost was Rs 17,464 (range: Rs 400-63,891). CONCLUSION: It is necessary to strengthen the inpatient care infrastructure and supporting diagnostic set-up, and work out economically optimized treatment algorithms for HIV-1-infected patients. Although this analysis does not cover all costs and may not be generalizable, these baseline data might be a useful reference while planning related studies accompanying the government-sponsored programme to roll out antiretroviral therapy to AIDS patients.

Autonomic dysfunction and peripheral vasodilatory response in diabetes.

Twenty three diabetes mellitus patients were investigated for peripheral vasodilatory response in relation to degree of autonomic dysfunction. The non-insulin dependent diabetes mellitus (NIDDM) patients had significant degree of autonomic dysfunction. Based on standard scoring system for evaluating autonomic dysfunction, diabetics were divided into 'borderline' (n = 12) and 'severe' (n = 11) diabetic autonomic neuropathy (DAN) groups. The severe DAN patients showed significantly lower pressor response when compared to borderline DAN patients. Severe DAN was also associated with significant peripheral vascular dysfunction. The severe DAN patients largely had no clinical manifestation of peripheral vascular dysfunction. Thus, at subclinical level patients with significant autonomic dysfunction do exhibit peripheral vascular dysfunction.