Chemioterapia : international journal of the Mediterranean Society of Chemotherapy最新文献

Recent studies reported in the literature have repeatedly pointed out the utility of imidazole derivatives, one of which is bifonazole, in the therapy of seborrheic dermatitis (SD). The cause of this pathological situation is still under discussion but the therapeutic success obtained with antimycotics speaks in favor of the pathogenetic importance of Malassezia ovale in this context. There is a high frequency of SD type complaints in patients with HIV infections in whom immune defenses against various pathogens, including yeasts, are deficient. We therefore verified the clinical efficacy of 1% bifonazole cream on 15 subjects with SD of the face, 9 of whom were affected with lymphadenopathy syndrome/AIDS-related complex (LAS/ARC). The treatment was administered over a four-week period and gave good results in 12 patients. The best results, however, were observed in those suffering from LAS/ARC.

The minimal inhibitory concentrations (MIC) and the minimal bactericidal concentrations (MBC) of xibornol against 100 strains of Staphylococcus aureus, clinically isolated, have been evaluated. Xibornol has shown very good in vitro activity and a significant uniformity of the results. In fact the inhibitory and bactericidal activity range was between 2 micrograms/ml and 8 micrograms/ml.

The pharmacokinetics of PTT-119, a new alkylating agent, was studied in 8 advanced cancer patients. PTT-119 disappeared rapidly from plasma after administration at a dose of 3 mg/kg by i.v. bolus injection. The HPLC method shows plasma levels of m-bis (dichloroethyl)amino-phenyl-L-alanine which is the major metabolite of PPT-119. Elimination of the drug from plasma can be described by a one-compartment model. Mean values of 77.8 min for the half-life, 510.8 ml/min for the total plasma clearance and 0.69 l/kg for the volume of distribution were found.

Forty-nine patients with localized osteosarcoma of the extremities were treated with a new protocol of neoadjuvant chemotherapy. Preoperatively the patients received high-dose methotrexate intravenously, followed after a week by cisplatinum intra-arterially for a continuous infusion over a 72-hour period, plus adriamycin intravenously infused over an 8-hour period. In all cases the clinical and radiographic response was good and in 44 cases (89.7%) it was possible to perform conservative surgery. The histologic examination of the surgical specimen resulted in necrosis being "good" (greater than or equal to 90% of necrosis) in 41 patients (83.6%). This percentage of "good necrosis" was significantly higher than the percentage previously obtained in our Center as well as in others for preoperative treatment of this tumor. Up to now, patients with localized osteosarcoma of the extremities who showed a good histologic response to the preoperative chemotherapy have had a very good prognosis (82% of patients are continuously disease-free). These results suggest that this new regimen represents a substantial improvement in the treatment of this disease.

Thirty patients with recurrent squamous cell carcinoma of the head and neck were treated with an outpatient schedule: cisplatin (100 mg/m2) day 1 and an 8-hour infusion of 5-fluorouracil (1000 mg/m2) on days 1-4 every 28 days. Twenty-eight patients were evaluable for response and toxicity: there were 5 complete responses (17.8%), 12 partial responses (42.8%), 6 stable disease (21.6%) and 5 progressions (17.8%). Patients with good performance status had a better response; patients who received prior chemotherapy had less positive responses. Median remission duration was 30+ weeks in patients who had a complete response, 25+ weeks in patients with a partial response. Median overall survival was 28+ weeks: 36+ weeks for responders and 14 weeks for non-responders. The major toxic effect was nausea/vomiting, while myelosuppression and stomatitis were less frequent and never severe.

The effects of different chemotherapy protocols on survival were evaluated in 197 small cell lung cancer patients followed-up between 1974 and 1987 in our unit. Of these, 170 patients had Stage IV disease and 24 had Stage III disease. Thoracic radiotherapy was given to 73 patients of whom 63 had Stage IV disease. Cytotoxic chemotherapy was given in four main protocols consisting of cyclophosphamide (CYC): CYC + vincristine (VCR); CYC + VCR + adriamycin (ADM) and CYC + VCR + ADM + lomustine (CCNU). The latter protocol was associated with the highest survival rates and differed significantly (p less than 0.05) from the others. In patients with extensive disease, both radiotherapy to the primary site and adjuvant immunomodulation in conjunction with the above chemotherapy regimens lacked any beneficial effect on survival.

Between March, 1983 and June, 1986, 32 patients with localized high grade osteosarcoma of the extremities who refused chemotherapy before surgery (neoadjuvant chemotherapy), were immediately operated on and treated with a protocol of adjuvant chemotherapy. This was performed with adriamycin, methotrexate, cisplatinum, bleomycin, cyclophosphamide and dactinomycin. At a median follow-up of 40 months (12-57), 20 patients (63%) remained continuously disease-free. These results appear to be better than the results achieved in our institution in 108 patients treated between 1980 and 1982 with an adjuvant chemotherapy protocol in which only adriamycin and methotrexate were employed. They also seem comparable to the results obtained in 127 contemporary patients treated with neoadjuvant chemotherapy in which the same drugs were used (methotrexate i.v., cisplatinum i.a. preoperatively; adriamycin- methotrexate- cisplatinum or adriamycin -bleomycin -cyclophosphamide-dactinomycin postoperatively, depending on the degree of necrosis achieved by preoperative treatment). These data seem to indicate that the improved survival with neoadjuvant chemotherapy compared to a previous group of patients treated with adjuvant chemotherapy may be related to the improved effectiveness of the agents used rather than the sequence of treatment.

The in vitro antibacterial activities of amoxycillin/clavulanate (Augmentin), ceftazidime and ceftriaxone were compared against 330 gram-negative and gram-positive strains isolated from clinical specimens received at the King Abdulaziz University Hospital (KAUH) in Saudi Arabia. The antibacterial susceptibility was determinated by Stokes method and by the minimal inhibitory concentration (MIC) using an agar dilution method. Ceftazidime and ceftriaxone were the most active antibiotics, inhibiting 90% of the tested strains by obtainable serum concentrations. Augmentin, on the other hand, had much lower activity against most of the strains tested. Ceftazidime's activity was superior to that of ceftriaxone especially against Klebsiella spp., Enterobacter spp., Citrobacter diversus, indole positive Proteus, Providencia stuartii, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Ceftriaxone had better activity against Serratia orderefera, Morganella morganii and Staphylococcus aureus. Beta-lactamase stable cephalosporins are therefore a potential replacement for aminoglycosides in the antimicrobial therapy of serious Gram-negative infections and alternative agents in the treatment of some Gram-positive infections.

We used single daily intravenous teicoplanin as therapy for 12 severe nosocomial infections caused by gram-positive bacteria. A daily dosage of 3-6 mg/kg was usually adopted; however, in selected cases the dosage was increased to 8-9.5 mg/day on the basis of serum bactericidal monitoring. Most of these infections were life-threatening and included ventriculitis/meningitis (3 cases), sepsis (3 cases), mediastinitis (1 case) and extensive burn wound infection (1 case). Staphylococcus aureus was by far the most frequent pathogen and methicillin-resistant strains were isolated in 7 out of 9 infections caused by this organism. The remaining isolates were Staphylococcus epidermidis, JK Corynebacterium, Streptococcus agalactiae and Propionilbacterium acnes. Additional antibiotics were used in 5 cases for concomitant gram-negative bacillus etiology (2 cases), granulocytopenia (2 cases), superinfection (1 case). Overall a clinical success and microbial eradication were documented in 100% and 91% of 12 cases, respectively. Except one case of fever, no other major adverse effect was observed and no patient required trial therapy discontinuation. In conclusion, our preliminary data seem to suggest a satisfactory activity of teicoplanin against nosocomial gram-positive infections.

In a controlled open study of 38 patients with acute pyelonephritis, treatment with fosfomycin 8 g b.i.d. was compared to treatment with ampicillin 2 g t.i.d., both for one week. The most common pathogen in both groups was Escherichia coli, susceptible to fosfomycin. However, 17% were resistant to ampicillin. The success rate was 44% in the fosfomycin treated group and 28% in the ampicillin group. The difference was not significant (p greater than 0.20). Peak concentrations of fosfomycin in serum were 395 mg/l and in tissue fluid 85 mg/l. Urine concentrations ranged from 6990 to 24,320 mg/l.