Home About us Contact
|
Home About us Contact | ||
|
|
||
Unacceptable Toxicity (unacceptable + toxicity)
Selected AbstractsPhase II study of S-1 and irinotecan combination chemotherapy as a first-line therapy for patients with advanced gastric cancer.ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Korean Cancer Study Group Protocol ST05-0 Abstract Background: Irinotecan plus intravenous 5-fluorouracil (5-FU) with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative and has a high response rate of about 40% for patients with advanced gastric cancer (AGC). We evaluated the antitumor activity and toxicities of an S-1 and irinotecan combination as a first-line therapy for patients with AGC. Methods: Patients with histologically confirmed unresectable or metastatic AGC were treated with S-1 40 mg/m2 PO twice daily on days 1,14 and irinotecan 150 mg/m2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities resulted. Results: A total of 45 patients were enrolled between September 2005 and March 2007. After a median of seven cycles of chemotherapy (range: 1,20, total: 350), 42 and 44 patients were evaluable for response and toxicity, respectively. On the intention-to-treat analysis, the overall response rate was 48.9% (95% C.I. 34.3,63.5%). The median time to progression was 5.7 months (95% C.I. 4.3,7.1) and the median overall survival was 10.4 months (95% C.I. 6.1,14.7). The commonly observed grade 3/4 adverse events were neutropenia (29.5% of patients) and vomiting (13.6%). Conclusion: An S-1 and irinotecan combination chemotherapy is active and tolerable as a first-line therapy for AGC. [source] Successful Treatment of Pediatric Psoriasis with Indigo naturalis Composite OintmentPEDIATRIC DERMATOLOGY, Issue 5 2006Yin-Ku Lin M.D. Many modes of therapy are currently in use but the disease is often resistant to treatment owing to the unacceptable toxicity that leads to poor compliance. Therefore, to develop an alternative treatment is indispensable. Traditional Chinese medicine has been documented for over 1000 years to provide various effective treatments for inflammatory skin diseases. Herein, we report an 8-year-old boy with recalcitrant pediatric psoriasis who, after multiple treatment failures with conventional antipsoriatic medications, showed remarkable clinical improvement with 8 weeks of topical treatment with Indigo naturalis composite ointment. Remission has lasted for over 2 years until now. Our patient's response suggests that topical Indigo naturalis composite ointment may provide a safe and effective alternative treatment for pediatric psoriasis. [source] A phase 2 pilot trial of low-dose, continuous infusion, or "metronomic" paclitaxel and oral celecoxib in patients with metastatic melanomaCANCER, Issue 7 2010Rupal S. Bhatt MD Abstract BACKGROUND: Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX-2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM. METHODS: Patients received paclitaxel 10 mg/m2 for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6-week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study. RESULTS: Twenty patients were enrolled. Twelve of 20 patients (60%) had received ,2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment-related grade 3/4 toxicities were limited to catheter-related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43-151 days), and the median overall survival was 212 days (95% confidence interval, 147-811 days). CONCLUSIONS: Low-dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010. © 2010 American Cancer Society. [source] Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma,,CANCER, Issue 5 2008A multicenter trial of the AIDS Malignancy Consortium Abstract BACKGROUND. Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS-275291, was evaluated in patients with human immunodeficiency virus-associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored. METHODS. Cohorts of 6 patients were to be treated with BMS-275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose-limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response. RESULTS. Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3,54 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation/de-escalation decisions utilizing the apoptosis assay was not feasible. CONCLUSIONS. BMS-275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better-tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus-associated KS. The apoptosis assay was not helpful in predicting response. Cancer 2008. © 2008 American Cancer Society. [source] Multi-institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high-grade gliomas,CANCER, Issue 5 2008Casilda Balmaceda MD Abstract BACKGROUND. The prognosis for patients with recurrent high-grade gliomas is poor and treatment options are limited. Current chemotherapeutic regimens can improve clinical outcomes, but extend survival by only a few months. Temozolomide is a methylating agent that is typically administered once daily. Because preclinical studies suggested that a twice-daily dosing schedule might be more effective, the safety and efficacy of twice-daily dosing of temozolomide were studied in patients with recurrent gliomas at their first, second, or third recurrence. METHODS. This multi-institutional trial enrolled 120 patients with recurrent glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO). An initial oral dose of 200 mg/m2 of temozolomide was followed by 9 consecutive doses of 90-mg/m2 every 12 hours. Treatment cycles were repeated every 28 days. Doses were escalated to 100 mg/m2 twice daily in the absence of unacceptable toxicity or were reduced if unacceptable toxicity occurred. RESULTS. For GBM, AA, and AO patients, respectively, the median progression-free survival (PFS) was 4.2 months, 5.8 months, and 7.7 months, whereas the median overall survival (OS) was 8.8 months, 14.6 months, and 18 months. The overall response rate (partial and complete) for the GBM, AA, and AO patients was 31%, 46%, and 46%, respectively. Grade 3/4 toxicities included neutropenia (1.1%), thrombocytopenia (3.6%), and anemia (0.3%) (graded according to the World Health Organization grading system). CONCLUSIONS. Twice-daily dosing may enhance the efficacy of temozolomide in the treatment of recurrent gliomas without increasing toxicity. This regimen compares favorably with other dosing schedules of temozolomide reported in the literature. Cancer 2008. © 2008 American Cancer Society. [source] High circulating HER2 extracellular domain levels correlate with reduced efficacy of an aromatase inhibitor in hormone receptor-positive metastatic breast cancer: A confirmatory prospective studyCANCER, Issue 10 2007Ramon Colomer MD Abstract BACKGROUND. In this specifically designed, prospective study, the authors addressed the predictive value of circulating levels of the extracellular domain (ECD) of HER2 in patients with metastatic breast cancer who were treated with letrozole. METHODS. Two hundred twenty-six patients with hormone receptor-positive, metastatic breast cancer received letrozole (2.5 mg daily) until they developed either disease progression or unacceptable toxicity. Efficacy was measured primarily as the time to progression (TTP) and, secondarily, as the objective response rate (ORR) and overall survival. HER2 ECD levels were determined by using a sandwich enzyme HER2/neu immunoassay before letrozole treatment was initiated. Positive HER2 ECD status was correlated with treatment efficacy. RESULTS. Forty-two patients (19%) had elevated HER2 ECD levels, which were associated with primary tumor HER2 expression (P < .001) but not with age, performance status, location, or number of metastatic sites. The median TTP was significantly shorter among patients who had elevated HER2 ECD compared with the median TTP among patients who had normal levels (4 months vs 14 months; P = .0004), and the ORR was lower in the group with elevated HER2 ECD levels (14% vs 30%; P < .036). Overall survival was significantly shorter among patients with elevated serum HER-2 ECD (P < .0005). CONCLUSIONS. Elevated HER2 ECD concentrations predicted poorer outcomes in postmenopausal women with metastatic hormone receptor-positive breast cancer who were treated with aromatase inhibitors like letrozole. © 2007 American Cancer Society. [source] | ||||||||||