Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of the raltitrexed plus oxaliplatin combination regimen, to explore its safety and pharmacokinetics, and to assess its antitumor activity in patients with advanced solid tumors. PATIENTS AND METHODS: Forty-eight patients received the combination of raltitrexed plus oxaliplatin. Raltitrexed was administered as a 15-minute infusion followed by oxaliplatin as a 2-hour infusion 1 hour later, repeated every 3 weeks. Seven dose levels were explored, ranging from 2 to 3.75 mg/m(2) and from 85 to 130 mg/m(2) for raltitrexed and oxaliplatin, respectively. The pharmacokinetics of both raltitrexed and oxaliplatin was assessed at the last three dose levels. RESULTS: Forty-six patients were assessable for toxicity. Severe toxicities usually occurred from dose level V (raltitrexed 3 mg/m(2) and oxaliplatin 130 mg/m(2)). This combination was not myelosuppressive, eliciting only sporadic grades 3 and 4 neutropenia and/or thrombocytopenia without complications. There was no alopecia. DLTs were asthenia and nausea/vomiting, despite systematic antiemetic prophylaxis. Dose level VI (raltitrexed 3.5 mg/m(2) and oxaliplatin 130 mg/m(2)) was deemed to be the MTD. Eight confirmed partial responses were observed: six patients with malignant mesothelioma (both pretreated and nonpretreated), one with fluorouracil-refractory pancreatic carcinoma, and one with renal carcinoma. Evaluation of the pharmacokinetics of both drugs did not suggest any drug interaction. CONCLUSION: The combination of raltitrexed and oxaliplatin given as consecutive short infusions every 3 weeks seems to be an acceptable regimen that allows a dose-intensity as high as the sum of the recommended doses of each agent given alone. The dose recommended for further phase II studies is raltitrexed 3 mg/m(2) and oxaliplatin 130 mg/m(2) every 3 weeks. Promising antitumor activity has been observed in patients with malignant mesothelioma.     

Tailored design of p-phenylenediamine functionalized graphene decorated with cobalt ferrite for microwave absorption

Structural design and componential optimization are two primary directions in the study of microwave absorbers. In this study, a novel cobalt ferrite (CoFe₂O₄) decorated with p-phenylenediamine (PPD) functionalized graphene (PG/CoFe₂O₄) binary hybrid with unique hierarchical porous structure was synthesized by a two-step route. The chemical composition, morphology and electromagnetic parameters of the as-prepared sample were investigated successively. The porous CoFe₂O₄ microspheres with an average diameter of about 160 nm were uniformly anchored on rGO nanosheets. Owing to the uniquely hierarchical porous structure, synergistic effects of dielectric loss (conductive loss, interface and dipole polarization) and magnetic loss (eddy current loss, natural and exchange resonance), the as-prepared sample exhibited excellent microwave absorption (MA) performance. The maximum reflection loss (RL_max) could attain up to −53.3 dB, and the effective absorption bandwidth (EAB) reached 6.6 GHz (11.4–18.0 GHz) at 2.40 mm, which completely covered the K_u band. These results showed that this functional material can be applied in the MA field.

A hierarchical porous PG/CoFe₂O₄ composite was designed with excellent microwave absorption performance.     

Landau-Kleffner syndrome: a rare auditory processing disorder series of cases and review of the literature

Objective

To describe the clinical presentation and treatment of 3 children with an Auditory Processing Disorder with an identifiable neurological cause: Landau-Kleffner syndrome [3]. This classical syndrome is well recognized in pediatric neurology but the diagnosis is less well known to Pediatric Otolaryngology, Speech Language Pathology and Audiology services.

Methods

Retrospective chart review of three patients with Landau-Kleffner syndrome.

Results

In all cases, pharmacological intervention led to clinical and electroencephalographic improvement, but all patients had long-term difficulty with understanding sounds in a noisy environment. Magnetic Resonance Imaging (MRI) of the brain was normal in all three patients. Their language disturbance improved over time. Speech language intervention was helpful in addressing communication difficulties arising from the auditory processing/receptive and expressive language disorder.

Conclusion

A multidisciplinary assessment is the key for early diagnosis, treatment and follow-up in patients with this syndrome.     

Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors.

BACKGROUND: The aim of this study was to investigate the tolerability, pharmacokinetic interaction and antitumor activity of gefitinib ("Iressa", ZD1839), an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor, combined with gemcitabine and cisplatin in chemotherapy-na?ve patients with advanced solid tumors. PATIENTS AND METHODS: This was an open-label feasibility trial evaluating two doses of gefitinib (250 and 500 mg/day) in combination with gemcitabine and cisplatin. Gefitinib was administered daily from day 2 onwards. Gemcitabine 1250 mg/m(2) was given on days 1 and 8 and cisplatin 80 mg/m(2) on day 1 for up to six 3-week cycles. Patients could then continue to receive gefitinib monotherapy. RESULTS: Eighteen patients were entered, nine at each gefitinib dose level. Two patients developed dose-limiting toxicity: one grade 3 convulsion (250 mg/day dose group) and one grade 3 rash (500 mg/day dose group). The most frequently occurring adverse events in the combination phase were vomiting (17 patients), asthenia (16), nausea (14), diarrhea (14) and skin rash (13). The most common grade 3/4 adverse events were vomiting (seven patients), asthenia (six), thrombocytopenia (six), diarrhea (five) and anorexia (five). Pharmacokinetic analyses showed no apparent pharmacokinetic interaction between gefitinib and cisplatin or gemcitabine, with the exception of a possible small increase in the geometric mean exposure to gemcitabine seen on day 8 of therapy when given alone with the higher dose of gefitinib. Of 17 evaluable patients, nine had confirmed partial responses, seven had stable disease and one had progressive disease. CONCLUSIONS: Combination therapy of gefitinib with cisplatin and gemcitabine had a manageable and predictable safety profile, no major effect on exposure to any of the three drugs and antitumor activity.     

Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin

Background: The combination of 5-fluorouracil (5-FU) and cisplatin hasshown great activity in many different types of tumour with an in vitrosynergistic effect between 5-FU and cisplatin. A phase II study of 5-FU pluscisplatin was performed in 25 previously untreated patients with inoperablelocally advanced or metastatic biliary tract carcinoma.Patients and methods: Twenty-five patients, 10 of them men and 15 womenwith a median age of 58, were entered into the study. The chemotherapyregimen consisted of 5-FU: 1 g/m²/day in continuousintravenous (i.v.) infusion for five consecutive days, and cisplatin: 100mg/m²/day on day 2 in a one-hour infusion with standardhyperhydration. Twenty-two patients had metastatic tumours and three hadlocally advanced disease.Results: Of the 25 patients entered into the study, 24 were evaluable forresponse and 25 for toxicity. Nausea and vomiting was the main toxic sideeffect in 19 patients. Severe, WHO grade 3–4 thrombocytopenia orneutropenia were observed in three and seven patients, respectively. Therewere no toxic deaths. Of 25 patients, six had partial remissions (overallresponse 24%, 95% confidence interval7%–41%). For three patients, tumour reduction permittedlocal radiotherapy and one of these patients with initially advanced diseaseis still alive six years after the beginning of treatment.Conclusions: This study, one of the largest phase II trials performed inthis disease, shows interesting activity of the combination of 5-FU andcisplatin in advanced biliary tract carcinoma.