Phase I study of gemcitabine and carboplatin in advanced non-small cell lung carcinoma.

BACKGROUND: This phase I study was designed to determine the maximum tolerated dose of carboplatin with a fixed dose of gemcitabine without growth factor or hematopoietic precursor support. METHODS: Nineteen patients with previously untreated non-small cell lung cancer (NSCLC) were treated at three dose levels. Initially, the gemcitabine dose was 1000 mg/m(2) given on days 1 and 8. Of the first five patients treated with carboplatin AUC 4, three experienced dose limiting toxicity (DLT). The study was, therefore, amended to decrease the dose of gemcitabine to 800 mg/m(2) given on days 1 and 8 in a 21-day cycle. RESULTS: Dose limiting toxicity (neutropenia and thrombocytopenia) were seen at dose level 2A (carboplatin AUC=5). Thus, no further dose escalation was performed. Grade 3 and 4 toxicities were seen as follows: leukopenia in five of 18 (28%); neutropenia, four of 18 (22%); and thrombocytopenia, four of 18 (22%) evaluable patients. Grade 3 or 4 anemia occurred in one of 18 (6%) patients and no neutropenic fever or treatment related mortality was observed. Partial responses were seen in six patients and one patient with evaluable disease had an objective response. The overall response rate was 37% (seven of 19). Six other patients had stable disease. A total of 89 courses were administered with a median of five courses per patient (range: two to six courses). The median time to progression for all patients was 3.7 months. The median overall survival was 7.4 months with four patients still alive (median follow up 13.5 months). The survival at 6 months and 1 year is 64 and 23%, respectively. CONCLUSION: The maximum tolerated dose (MTD) in this group of patients was defined as carboplatin AUC 4 when administered with gemcitabine 800 mg/m(2) on days 1 and 8 of a 21-day schedule.

Age and intrinsic left ventricular myocardial contractility.

The purpose of this study was to compare the left ventricular (LV) intrinsic contractile function in normal elderly (age > or = 60 years, mean age 66 +/- 4 years) and young (age < or = 35 years, mean 27 +/- 9 years) healthy volunteers by stress-shortening and stress-length relationship using a co-variate analysis. Echocardiographically determined meridional and circumferential wall stress were plotted against LV fractional shortening, velocity of circumferential fibre shortening, end-systolic volume and diameter. LV ejection fraction, preload (denoted by end-diastolic volume) and afterload (expressed as circumferential wall stress) were similar in the two groups. Stress-shortening and stress-length relationships using the circumferential wall stress showed no difference in the two groups, although meridional wall stress was greater in the elderly population. Our results suggest that circumferential wall stress is a better method to detect intrinsic contractile abnormality in the elderly. Intrinsic LV ejection performance is within the normal range in the elderly healthy individuals.

Severe Isospora (Cystoisospora) belli Diarrhea Preceding the Diagnosis of Human T-Cell-Leukemia-Virus-1-Associated T-Cell Lymphoma.

Isospora (Cystoisospora) belli diarrhea can sometimes be fulminant in immunocompromised patients. It is endemic in tropical and subtropical areas, and sporadic episodes have been reported in nonendemic areas in nursing homes, day-care centers, and psychiatric institutions. We describe isosporiasis in an HIV-negative Sudanese-American female who presented with a debilitating diarrheal illness and profound weight loss. Isospora belli was detected in her stool by modified acid-fast staining. Serologic testing was negative for HIV but positive for HTLV-1 infection. Treatment with TMP-SMZ led to improvement in her diarrhea which recurred after stopping antibiotics. Subsequently, she developed generalized lymphadenopathy which was diagnosed as ATLL on immunohistochemical staining. Chemotherapy was initiated, but her condition continued to worsen due to persistent diarrhea and resulting profound electrolyte abnormalities. The patient opted for comfort measures and died a few weeks later at a nursing facility. This case emphasizes that the detection of I. belli should trigger testing for HIV, HTLV-1, and other causes of immunocompromise. We suggest that treatment with TMP-SMZ should be initiated and continued for a prolonged period of time in immunocompromised patients with I. belli diarrhea.