[Transcutaneous absorption of industrial toxic substances]. / Assorbimento transcutaneo dei tossici industriali.

Percutaneous absorption of industrial toxic agents has been emphasized in the last decade, in particular because the use of effective environmental and individual preventive measures has greatly reduced risks by inhalation. The aim of this paper is to summarize the main methods currently in use for the assessment of percutaneous absorption: in vivo and in vitro studies, use of cutaneous substitutes, techniques of removal, fluorescent techniques, indirect methods and biological monitoring. Currently there are no limit values of cutaneous exposure, except for the skin notation suggested by ACGIH, and it is necessary to analyze and standardize the methods for its assessment to guarantee the applicability of these methods to all industrial activities. Moreover it is necessary to increase the low perception of cutaneous risk, to correct the wrong use of DPI and the wrong individual hygienic habits.

Phase II study of gemcitabine, 5-fluorouracil, and leucovorin in patients with pancreatic cancer.

The primary goal of this phase II study was to determine the efficacy of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil in patients with pancreatic cancer. Eligibility criteria included nonresectable locally advanced or metastatic pancreatic adenocarcinoma and measurable disease. Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every 4 weeks. Twenty nine patients were enrolled. The overall response rate was 21% (95% confidence interval: 8% to 40%), consisting of one complete response and five partial responses; 16 patients (55%) had stable disease. Median survival was 8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was generally of short duration. No thrombocytopenia or evidence of cumulative myelosuppression was observed. The only significant nonhematologic events were grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is active and well tolerated compared with results reported for each of these single agents. Thus, this combination justifies future comparative clinical trials. Semin Oncol 28 (suppl 10):44-49.

A randomised phase II study of oxaliplatin alone versus oxaliplatin combined with 5-fluorouracil and folinic acid (Mayo Clinic regimen) in previously untreated metastatic colorectal cancer patients.

The aim of this study was to examine the efficacy and safety of both oxaliplatin as a single agent and oxaliplatin in combination with dailyx5 bolus 5-fluorouracil and folinic acid (5-FU/FA, Mayo clinic regimen) in the first-line treatment of metastatic colorectal cancer (CRC) patients. 73 advanced CRC patients were randomised to receive either oxaliplatin 85 mg/m(2) every 2 weeks (35 patients), or the same treatment combined with 5-FU 425 mg/m(2)/day and FA 20 mg/m(2)/dayx5 days every 4 weeks (38 patients). Treatment was continued until disease progression or unacceptable toxicity. All patients had documented inoperable disease and no previous chemotherapy for advanced disease. Based on the investigators' assessment of best response, objective response rate was 9% (95% confidence interval (CI) 2-24%) in the oxaliplatin arm, and 45% (95% CI 27-64%) in the oxaliplatin+5-FU/FA arm. Median progression-free survival (PFS) was 2 months (95% CI 1.7-2.4 months) in the oxaliplatin arm and 3.9 months (95% CI 2.9-5 months) in the oxaliplatin+5-FU/FA arm. Severe neutropenia was seen in 23% of patients in the oxaliplatin+5-FU/FA arm, and none in the oxaliplatin arm. There were two treatment-related deaths, both in the oxaliplatin+5-FU/FA arm. In the oxaliplatin+5-FU/FA arm, severe diarrhoea, vomiting and stomatitis were seen in 34, 14 and 14% of the patients, respectively. In conclusion, oxaliplatin at a dose of 85 mg/m(2) given every 2 weeks was well tolerated and has limited activity in metastatic CRC, while the combination of this treatment with the full-dose Mayo clinic regimen (5-FU bolus 425 mg/m(2)/day+FA 20 mg/m(2)/dayx5 days every 4 weeks), although active, was unfeasible due to a high level of myelosuppression and gastrointestinal toxicity. Alternative lower dosing or other regimens are to be explored to ascertain the value of bolus 5-FU/FA combined with oxaliplatin.

Phase II of doxorubicin/taxol in metastatic breast cancer. Argentine Multicenter Taxol Group.

PURPOSE: To assess the response rate, survival, and toxicity of Taxol (paclitaxel) as 1-h infusion plus doxorubicin as first-line treatment for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Seventy-six patients with untreated MBC were recruited. All of them had measurable disease and were evaluable for toxicity. Fifty-five percent of the patients had visceral involvement. The dose of doxorubicin was fixed at 50 mg/m2 as a short intravenous infusion, followed by 200 mg/m2 of Taxol as a 1-h intravenous infusion. Doxorubicin was administered during the first seven cycles, continuing with Taxol only up to a maximum of ten cycles. RESULTS: Neutropenia was the most important toxicity: 30% grade 3 and 18% grade 4. Only 2 patients showed a decrease in the left ventricular ejection fraction (LVEF) which caused discontinuing the treatment. No clinical congestive heart failure (CHF) was observed. Seventy-four patients were eligible for response evaluation: 10 (14%) achieved complete response (CR) and 46 (62%) achieved partial response (PR). The mean duration of response was 13.47+/-1.35 months (95% confidence interval (CI): 10.82; 16.12) and the mean survival was 21.50+/-1.42 months (95% CI: 18.72; 24.29). CONCLUSION: The overall response (OR) rate was 76%. No CHF was assessed and 2 patients stopped treatment due to LVEF decrease. Although doxorubicin 50 mg/m2 followed by Taxol 200 mg/m2 in 1-h intravenous infusion presents a toxicity profile which demands a close follow-up, it represents a convenient outpatient schedule with similar activity rate compared to longer Taxol infusions.

A prospective, randomized Phase III trial comparing combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil with vinorelbine plus doxorubicin in the treatment of advanced breast carcinoma.

BACKGROUND: A prospective, multicenter, randomized, Phase III trial comparing the efficacy of combination chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with a combination of vinorelbine and doxorubicin (NA) in the treatment of patients with advanced breast carcinoma was undertaken. METHODS: One hundred and seventy-seven patients who previously were untreated for recurrent or metastatic breast carcinoma were entered into the study; 7 patients could not be assessed. The final analysis relates to 85 patients who were treated with FAC and 85 patients who were treated with NA, of whom 21 (25%) and 44 (52%), respectively, had received prior adjuvant chemotherapy. RESULTS: The overall response rates were similar for the two treatments and were unaffected by prior exposure to adjuvant therapy; overall response rate (ORR) for FAC was 74% (95% confidence interval [95% CI], 65-83%), and the ORR for NA was 75% (95% CI, 66-84%). The activity of NA in patients with liver involvement was greater than that of FAC in terms of survival. Overall survivals were similar, with a median of 17.3 months for patients receiving FAC and 17.8 months for patients receiving NA. Severe toxicity was uncommon with World Health Organization Grade 3-4 neutropenia affecting only 7% of patients in each arm of the study. NA was associated with a higher incidence of mild to moderate constipation, neurotoxicity, and phlebitis, whereas FAC produced a slight excess of mild cardiotoxicity. CONCLUSIONS: The efficacy of these two regimens is very similar, although NA may be more active in a subset of patients with visceral metastatic disease, particularly liver involvement. It is clear that, in a direct comparison with an established three-drug regimen, the newer two-drug combination of NA demonstrated equivalent activity with no significant excess of Grade 3-4 toxicity.

Treatment of non-small cell lung cancer with ifosfamide (IFO)+ 4'-epiadriamycin (EPI)+platinum vs. IFO+EPI: a GETLAC Study. Grupo de Estudio y Tratamiento Latinoamericano del Cáncer Study.

203 patients with inoperable non-small cell lung cancer (NSCLC) were randomized to receive ifosfamide (IFO) 2.5 g/m2 days 1-2 + epirubicin (EPI) 70 mg/m2 day 1 with cisplatin (DDP) 70 mg/m2 day 1 (arm IEP), or without cisplatin (arm IE). For uroprophylaxis, mesna i.v. 20% of IFO dose, hour 0 and 3, and oral, 40% of IFO dose, hour 6 and 9, days 1-2 was given. Cycles were repeated every 28 days. Four cycles were required for evaluation purposes. After completion of chemotherapy, external beam irradiation 40 Gy was given over 4 weeks for stage III B responders. Most of the patients with stable disease, partial response or complete response (CR) received 6 cycles. The median follow-up of the trial is 30 months. There were no differences in overall response rates: arm IEP: 52% (2% CR); arm IE: 51% (13.5% CR). Median time to progression was 6 months (arm IEP) and 4 months (arm IE) (p = 0.4844). Toxicity ranged from mild to moderate. Nephrotoxicity was not seen; only 6 patients had neurotoxic side effects of short duration. Median survival according to treatment was 12 months for IEP arm (12% at 2 years) and 10 months for IE arm (21% at 2 years). IFO/mesna+EPI or IFO/mesna, EPI plus DDP appeared to be an active and well tolerated combination for the treatment of NSCLC, with a good survival time.

Tratamiento sistémico del cáncer avanzado de ovario con interferón ß y quimioterapia / Systematic treatment of the advanced ovarian cancer with ß interferon and chemotherapy

El cáncer de ovario es una de las causas de muerte más común dentro de las neoplasias ginecológicas, por lo que los tratamientos de rescate son de considerable interés; así, se desarrollaron tratamientos con esquemas que contienen platino, de elección en estadios avanzados. En nuestra presente experiencia encontramos que la combinación carboplatino-ifosfamida, mesna, 4 epirrubicina y el interferón ß es una alternativa efectiva y tolerable, pues 4 de las pacientes obtuvieron respuesta completa luego de la cirugía de rescate. Para obtener conclusiones definitivas, es necesario un mayor número de pacientes y tiempo de observación.

Tratamiento sistémico del cáncer avanzado de ovario con interferón ß y quimioterapia / Systematic treatment of the advanced ovarian cancer with ß interferon and chemotherapy

El cáncer de ovario es una de las causas de muerte más común dentro de las neoplasias ginecológicas, por lo que los tratamientos de rescate son de considerable interés; así, se desarrollaron tratamientos con esquemas que contienen platino, de elección en estadios avanzados. En nuestra presente experiencia encontramos que la combinación carboplatino-ifosfamida, mesna, 4 epirrubicina y el interferón ß es una alternativa efectiva y tolerable, pues 4 de las pacientes obtuvieron respuesta completa luego de la cirugía de rescate. Para obtener conclusiones definitivas, es necesario un mayor número de pacientes y tiempo de observación. (AU)