Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study.

To evaluate the efficacy and toxicity of irinotecan (CPT-11) in combination with raltitrexed as first-line treatment of advanced colorectal cancer (CRC). A total of 91 previously untreated patients with advanced CRC and measurable disease were enrolled in this phase II study. The median age was 62 years (range 31-77); male/female 54/37; ECOG performance status was 0 in 50 patients (55%), one in 39 (43%) and two in two (2%). Treatment consisted of CPT-11 350 mg x m(-2) in a 30-min intravenous infusion on day 1, followed after 30 min by a 15-min infusion of raltitrexed 3 mg x m(-2). Measurements of efficacy included the following: response rate, time to disease progression and overall survival. Of the 83 evaluable patients valuable to objective response, there were five complete responses (6%) and 23 partial responses (28%), for an overall response rate of 34% (95% CI: 25.9-46.5%). In all, 36 patients (43%) had stable disease, whereas 19 (23%) had a progression. The median time to progression was 11.1 months and the median overall survival was 15.6 months. A total of 487 cycles of chemotherapy were delivered with a median of five per patient. Grade 3-4 WHO toxicities were as follows: diarrhoea in 13 patients (15%), nausea/vomiting in four (4%), transaminase increase in six (7%), stomatitis in two (2%), febrile neutropenia in three (3%), anaemia in five (6%) and asthenia in three (3%). The combination CPT-11-raltitrexed is an effective, well-tolerated and convenient regimen as front-line treatment of advanced CRC.

Time-dose-response relationships in postoperatively irradiated patients with head and neck squamous cell carcinomas.

BACKGROUND AND PURPOSE: To define the influence of the dose and time on the response to treatment in postoperatively irradiated head and neck cancer patients and to establish a good prediction of failure. METHODS AND MATERIALS: From January 1985 to December 1995, 214 patients with histologically proven head and neck squamous cell carcinomas were irradiated after radical surgery or single tumour resection according to surgical and histopathological findings. The total doses given ranged between 50 and 75 Gy to the primary bed tumour and between 42 and 56 Gy to the neck with fraction sizes of 1.7-2 Gy/day. The median length of the time interval between surgery and radiotherapy, time of irradiation and total treatment time were 81, 59 and 139 days, respectively. The end-point analyzed was the local-regional tumour control rate at the primary tumour bed and neck for 5 years from the beginning of radiotherapy. Univariate and multivariate analyses were used to determine predictors of failure from among the following studied variables: (i), clinical stage (T/N) of the patients; (ii), tumour grade; (iii), neck surgery; (iv), tumour margins; (v), histological tumour nodal extension; (vi), chemotherapy; (vii), normalized total dose; (viii), time interval between surgery and radiotherapy; (ix), time of irradiation; and (x), total treatment time. RESULTS: The actuarial 5-year tumour control rate for the entire group was 72%, and 92% of the patients who achieved local control are currently alive without disease. Tumour control was inversely related to T stage (83% for T2 vs. 57% for T4) and the probability of local control within each stage was dependent on the N status (> or =71% for T3-T4/N0 vs. 31-44% for T3-T4/N1-N3). Histological N status and tumour margins, but not tumour grade, impacted significantly on tumour control. When local control was analyzed as a function of the dose to the primary, a non-significant negative dose-response relationship was found. The total treatment time was a significant prognostic factor, and the time interval between surgery and irradiation proved to be an independent predictor of failure. CONCLUSIONS: Despite the absence of a statistically significant dose-response relationship, the present results suggest that postoperative irradiation treatment given to patients with head and neck squamous cell carcinomas should not be unduly prolonged, in order to minimize the amount of tumour cell proliferation. In these patients, nodal involvement, positive margins of the resected specimens and time interval between surgery and irradiation were the most important prognostic factors.

Periodontal tissue disposition of azithromycin.

The tissue penetration of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients undergoing surgery for third-molar removal. Drug concentrations in plasma, saliva, and periodontal tissues were evaluated in 28 patients treated with azithromycin 500 mg/day per os for 3 consecutive days. Samples of blood, saliva, gingiva, and alveolar bone were collected during oral surgery, 12 hours, and 2.5, 4.5, and 6.5 days after the last dosing, and the azithromycin concentration was measured microbiologically by using Micrococcus luteus NCTC 8440 as the reference organism. The highest concentrations of azithromycin were observed 12 hours after the last dose in plasma, saliva, gingiva, and bone (0.33 +/- 0.04 mg/l, 2.14 +/- 0.30 mg/l, 6.47 +/- 0.57 mg/kg, and 1.86 +/- 0.15 mg/kg, respectively) and then declined gradually. However, consistent levels of the drug in saliva and periodontal tissues could be detected up to 6.5 days, indicating that azithromycin was retained in target tissues and fluids for a long time after the end of treatment. Among the samples examined, the highest concentration of azithromycin was found in the gingiva at each time studied. Moreover, the ratios of salivary or periodontal tissue levels versus plasma concentrations remained nearly unmodified from 12 hours up to 6.5 days. Overall, these results indicate a favorable disposition of azithromycin into saliva and periodontal tissues and suggest that this macrolide antibiotic represents a valuable option in the pharmacologic treatment of odontogenic infections.

[Changes in heroin administration route and frequency of human immunodeficiency virus infection]. / Cambios en la vía de administración de la heroína y frecuencia de infección por el virus de la inmunodeficiencia humana.

BACKGROUND: Self-administration of drugs by different intravenous routes may induce a reduction in the organic complications of drug addiction (DA). The aim of this study was to evaluate the changes in the way of drug administration in a series of DA individuals in the province of Cádiz, Spain, and the evolution of the frequency of infection by the human immunodeficiency virus (HIV) in these patients. METHODS: The reports of all the drug users from the province of Cádiz admitted to the Detoxication Unit of the Hospital Punta de Europa in Algeciras, from January, 1989 to July, 1993 were reviewed. At the time of admission many data were evaluated, fundamentally the main route of drug administration, and anti-HIV seropositivity. RESULTS: Seven hundred ten drug users were included in the study. Ninety-seven percent used mainly heroin. The route of drug administration on admission was intravenous in 56.1%, pulmonary in 39.7%, inhalatory in 3.2% and oral in 0.8%. Forty-one point seven percent patients were seropositive for HIV. The frequency of the use of the intravenous route throughout the semesters analyzed was I/89: 85.7%, II/89: 89.6%, I/90: 80%, II/90: 80.8%, I/91: 59.8%, II/91: 50%, I/92: 44.9%, II/92: 39%, I/93: 34.3% (p < 0.00001). The use of the respiratory route significantly increased. The percentage of anti HIV positivity in the drug users evaluated was 67.4, 80.8, 56.4, 46.9, 40.7, 34.1, 30.6, 36.3, 23.2% (p < 0.00001), respectively for the same periods. The decrease in the use of the intravenous route and the reduction in anti HIV seropositivity demonstrated a correlation coefficient of 0.91 with a confidence interval from 0.62 to 0.98 (p < 0.05). CONCLUSIONS: The decrease, over time, in the use of the intravenous route for heroin administration in the collective analyzed was significantly associated with a decrease in HIV infection in these patients.