Multicenter non-randomized phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients.

BACKGROUND: This multicenter, phase II, open-label study evaluated the antitumor efficacy and safety of oxaliplatin and raltitrexed (Tomudex) in non-pretreated advanced colorectal cancer patients. PATIENTS AND METHODS: Seventy-one patients received oxaliplatin 130 mg/m(2) and raltitrexed 3 mg/m(2) intravenously on an outpatient basis every 3 weeks. All patients had histologically proven metastatic colorectal adenocarcinoma, performance status 相似文献   

Topotecan vitreous levels after periocular or intravenous delivery in rabbits: an alternative for retinoblastoma chemotherapy

PURPOSE: To determine the extent and the mechanism by which topotecan, a candidate agent for the treatment of retinoblastoma, gains access to the vitreous when administered by periocular injection or intravenous infusion. METHODS: In vivo experiments were conducted in which albino rabbits received 1 mg topotecan by periocular injection (POI group; n = 30) or as a 30-minute intravenous infusion (IV group; n = 16). Plasma and vitreal topotecan concentrations were analyzed during the 10 hours after administration. A population pharmacokinetic model was fit to the data. Additionally, periocular injections were performed postmortem to study the effect of removing the blood vasculature barrier. RESULTS: Potentially active lactone topotecan levels were detected in the vitreous in the POI and IV groups. Both administration schedules induced high total topotecan plasma exposures because of absorption from the periocular depot, though plasma lactone area under the curve (AUC) was significantly higher in the IV group. Similar vitreal concentrations were found in treated and control eyes in the POI group. The transfer from the periocular compartment to the vitreous was negligible. The absence of drug levels in the control eye of the postmortem-injected rabbits confirmed the systemic delivery of topotecan. Local toxicity was not observed. CONCLUSIONS: As a consequence of a favored passage across the blood-retinal barrier, considerable topotecan vitreous levels were detected in a rabbit model after systemic or periocular administration. Transscleral entry in vivo was constrained by rapid clearance from the administration site.     

Phase II window of idarubicin in children with extraocular retinoblastoma.

PURPOSE: The aim of this study was to evaluate in an upfront phase II study the response to idarubicin in children with extraocular retinoblastoma. PATIENTS AND METHODS: The starting dose of idarubicin was 15 mg/m(2)/d (days 1 and 2) weeks 0 and 3. After an interim evaluation, the dose was reduced to 10 mg/m(2)/d (days 1 and 2) weeks 0 and 3 because of hematopoietic toxicity. Response was evaluated at week 6. RESULTS: At the Hospital JP Garrahan (Buenos Aires, Argentina), 10 patients (five bilateral) were entered onto the study from 1995 to 1998. A total of 19 cycles were administered. Extraocular sites included orbit (n = 10), bone marrow (n = 3), bone (n = 1), lymph node (n = 1), and CNS (n = 1). The response rate was 60% (95% confidence interval, 30% to 90%). One complete response was achieved, in addition to five partial responses, two cases of stable disease, and two cases of progressive disease. All patients with bone marrow involvement achieved complete clearance of tumor cells. The patient with CNS disease had progressive disease. All patients had severe hematopoietic toxicity (grade 4 neutropenia and grade 3/4 thrombocytopenia after most cycles). Other toxicities included grade 2 diarrhea in 30%. No echocardiographic changes were detected. CONCLUSION: Idarubicin is active in extraocular retinoblastoma. The activity of this drug should be explored in future phase III studies.     

How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP)

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.     

Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1.

PURPOSE: The purpose of this study was to determine whether the addition of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE) to standard first-line gemcitabine and cisplatin provides clinical benefit over gemcitabine and cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase II trials in pretreated patients, and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability. PATIENTS AND METHODS: This was a phase III randomized, double-blind, placebo-controlled, multicenter trial in chemotherapy-naive patients with unresectable stage III or IV NSCLC. All patients received up to six cycles of chemotherapy (cisplatin 80 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 of the 3-week cycle) plus either gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. Daily gefitinib or placebo was continued until disease progression. End points included overall survival (primary), time to progression, response rates, and safety evaluation. RESULTS: A total of 1,093 patients were enrolled. There was no difference in efficacy end points between the treatment groups: for the gefitinib 500 mg/d, gefitinib 250 mg/d, and placebo groups, respectively, median survival times were 9.9, 9.9, and 10.9 months (global ordered log-rank [GOLrank] P =.4560), median times to progression were 5.5, 5.8, and 6.0 months (GOLrank; P =.7633), and response rates were 49.7%, 50.3%, and 44.8%. No significant unexpected adverse events were seen. CONCLUSION: Gefitinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efficacy over gemcitabine and cisplatin alone. The reasons for this remain obscure and require further preclinical testing.     

Reoperation after lumbar disc surgery: Results in 130 cases

Summary Out of a series of 1850 cases operated upon for lumbar disc herniation 130 underwent re-operation because of persistent or recurrent symptoms. Re-operation was successful in 62%. The prognosis of re-operation was not related to special clinical symptoms and signs but only to the operative findings.Herniations at other levels and recurrences of lumbar disc herniations had the best results (excellent in 98% respectively 54%), but scar formations alone came out much less satisfactory (only 38% excellent results).Computed tomography (CT) findings were less reliable in distinguishing between disc prolapse and fibrosis than magnet resonance imaging (MR). Therefore MR is the diagnostic method of choice in these conditions, and scar formations alone should be considered a contra-indication for re-operation.     

Gas chromatographic-mass spectrometric detection of anhydroecgonine methyl ester (methylecgonidine) in human serum as evidence of recent smoking of crack

The discrimination between smoking of crack and other routes of cocaine application has forensic implications. The pyrolysis product anhydroecgonine methyl ester (AEME, methylecgonidine) has been found to be a marker for smoked cocaine. An improved method for the determination of AEME in serum was developed, consisting of mixed phase solid-phase extraction and GC-MS. Special care was taken for the volatility of AEME and tert.-butyldimethylsilylation was used for derivatization. Thus AEME could be determined for the first time in 13 serum samples from living subjects. The concentrations found were in a range of 3 to 34 ng/ml, a correlation with the storage time of the samples or with benzoylecgonine concentrations could not be found.     

Results of a prospective study for the treatment of retinoblastoma

BACKGROUND: The objectives of this prospective study were to avoid adjuvant treatment for patients with intraocular disease and patients with postlaminar optic nerve invasion (PL-ONI) without full choroidal or scleral invasion. Adjuvant chemotherapy (Regimen 1) was given to patients with scleral invasion, PL-ONI without cut section, and full choroidal and/or scleral invasion. A more intensive regimen of higher dose intravenous chemotherapy (Regimen 2) and local radiotherapy was given to patients with PL-ONI and compromise at the cut end and to patients with overt extraocular disease. METHODS: Six-month intravenous chemotherapy included carboplatin plus etoposide alternating with cyclophosphamide plus vincristine (Regimen 1) and the same drugs at higher dosage plus idarubicin (Regimen 2). Chemoreduction with carboplatin and vincristine with or without etoposide was given to selected patients (n = 39 patients). RESULTS: From 1994 to 2001, 169 patients were evaluable at the Hospital Garrahan (Buenos Aires, Argentina). One hundred eighteen patients with intraocular disease had a 5-year disease free survival (DFS) rate of 0.98, including 54 patients with choroidal invasion. None of 22 patients with isolated PL-ONI developed recurrent disease, whereas 2 of 8 patients with concomitant risk factors had tumor recurrences and died. Three of 5 patients with scleral invasion survived, and 7 of 10 patients with cut-end ONI survived. The only patient with metastatic disease that survived (n = 6) had only lymph node invasion. CONCLUSIONS: Adjuvant therapy can be avoided in patients with intraocular and isolated PL-ONI. Patients with PL-ONI who also had other risk factors required intensive adjuvant therapy, such as patients with cut-end and overt extraocular disease. Metastatic disease was not found to be curable with this approach.