Chemotherapy for brain metastases in small-cell lung cancer

PURPOSE: Brain metastasis occurs commonly in patients with small-cell lung cancer (SCLC). Herein, we report the efficacy of irinotecan and carboplatin in the treatment of brain metastases from SCLC. In addition, we review the existing data on chemotherapy for brain metastases in SCLC. PATIENTS AND METHODS: Eighty patients with metastatic or relapsed SCLC were enrolled in a phase II trial of irinotecan and carboplatin. Patients naive to chemotherapy were treated with irinotecan 200 mg/m2 and carboplatin AUC of 5, and patients previously treated with chemotherapy received irinotecan 150 mg/m2 and carboplatin AUC of 5, every 21 days for 6 cycles. RESULTS: Among the 80 patients, 15 (19%) presented with brain metastases. An analysis of 14 assessable patients with brain metastases revealed an overall response rate of 65% after 2 cycles of chemotherapy and a median survival of 6 months (range, 1-24 months). Upon review of the literature, 8 studies were identified as having > 10 patients who received chemotherapy for brain metastases from SCLC. Based on these studies, the response rate of brain metastases from SCLC to a variety of chemotherapy and median survival of patients ranged from 22% to 85% and 3 months to 9 months, respectively. CONCLUSION: Chemotherapy, including the regimen of irinotecan and carboplatin, is an effective treatment for SCLC brain metastases.     

Adjuvant treatment of stage IB NSCLC: the problem of stage subset heterogeneity

While 5-year survival rates in patients with stage IB non-small-cell lung cancer (NSCLC) are historically modest (40% to 67%), adjuvant chemotherapy trials including this subgroup have shown little evidence of chemotherapeutic benefit. This article reviews the available data regarding adjuvant chemotherapy following surgically resected stage IB NSCLC, framed within the context of present and future proposed definitions of this diagnosis. The discussion addresses limitations of the current staging system and how this contributes to the mixed results seen with adjuvant treatment. In addition, the authors consider current treatment options for stage IB NSCLC and review planned clinical trials for stage I disease designed to exploit new pharmacogenomic findings.     

Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus–infected rhesus macaques on antiretroviral therapy

Proliferation of latently infected CD4⁺ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4⁺ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA–treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4⁺ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.     

Contact lens related corneal ulcers at the Ohio State University Hospitals 1983-1987

We reviewed the records of patients with ulcerative keratitis associated with contact lens wear admitted to The Ohio State University Hospitals from January 1, 1983 through December 31, 1987. Of 127 cases of infectious ulcerative keratitis, 25 (19%) were associated with the use of contact lenses. Of these 25, 21 cases (84%) were associated with the use of soft lenses (40% aphakic, 40% cosmetic). Seventy-six percent (19 of 25) were culture-positive; Pseudomonas was the most common isolate (12 of 19, 63% of culture-positive cases). When compared with daily wear soft contact lenses, cosmetic and aphakic extended wear contact lens related ulcers were associated with a delay in definitive diagnosis and a worse prognosis. Patching and steroid use were associated with more severe ulcers. Gram stain findings were of value only when gram-negative rods were noted. The findings emphasize the need for patients to understand: 1) the risks of extended wear; 2) the necessity of removing the lenses at the first sign of irritation; and 3) the importance of having prompt, intensive care readily available.