6 research outputs found
Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma
<p>Abstract</p> <p>Background</p> <p>In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents.</p> <p>Methods</p> <p>Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment.</p> <p>Results</p> <p>Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034).</p> <p>Conclusions</p> <p>Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.</p
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Background
Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving
patients with previously treated metastatic melanoma. We conducted a phase 3 study
of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously
untreated metastatic melanoma.
Methods
We randomly assigned 502 patients with previously untreated metastatic melanoma,
in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per
square meter of body-surface area) or dacarbazine (850 mg per square meter) plus
placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks
through week 22. Patients with stable disease or an objective response and no doselimiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as
maintenance therapy. The primary end point was overall survival.
Results
Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1
months, with higher survival rates in the ipilimumab–dacarbazine group at 1 year
(47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard
ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of
patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated
with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal
perforations occurred in the ipilimumab–dacarbazine group.
Conclusions
Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as
compared with dacarbazine plus placebo, improved overall survival in patients with
previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were
lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb;
ClinicalTrials.gov number, NCT00324155.
Leishmaniasis in the Tongue of an Immunocompetent Man
A 49-year-old immunocompetent white man had a painful ulcer (1.5 cm in diameter) on the left ventrolateral surface of a grossly enlarged tongue. The ulcer was present for two months. Impaired swallowing resulted in substantial weight loss and fatigue. Histopathologic analysis of a punch biopsy specimen indicated numerous Leishman Donovan bodies within macrophages. A polymerase chain reaction confirmed the presence of L. donovani. Therapy with two cycles of liposomal amphotericin B over a three-month period was administered. Four months after discharge, the ulcer had healed completely and the tongue returned to its normal size and function
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma
BACKGROUND: Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. METHODS: We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no dose-limiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. RESULTS: Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab-dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab-dacarbazine group. CONCLUSIONS: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155.)