Raltitrexed plus oxaliplatin (TOMOX) as first-line chemotherapy for metastatic colorectal cancer. A phase II study of the Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD).

BACKGROUND: To evaluate the safety and efficacy of the novel raltitrexed/oxaliplatin combination (TOMOX) as first-line chemotherapy for patients with advanced colorectal cancer. MATERIALS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 3 mg/m2 plus oxaliplatin 100 mg/m2, both intravenously, on day 1 every 3 weeks. Patients were re-evaluated after every third cycle and chemotherapy was continued up to tolerance or disease progression. RESULTS: Fifty-eight patients from 13 Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD) centers were accrued from September 1999 to November 2000. According to the intention-to-treat analysis from 58 patients, the overall response rate was 50% [95% confidence interval (CI) 38% to 62%], with three complete responses and 26 partial responses. The median overall survival (44 patients currently alive) was >9 months and the median time to disease progression was 6.5 months (range 1-15 months). The main hematological toxicity was grade III/IV neutropenia, which occurred in 17% of patients, while anemia and thrombocytopenia were uncommon. Grade III/IV non-hematological toxicities were transient transaminitis (17% of patients); asthenia (16% of patients); neurotoxicity (10% of patients) and diarrhea (7% of patients). No toxic death was observed, one patient with grade IV asthenia after the first cycle refused chemotherapy. CONCLUSIONS: The results of this study suggest that the TOMOX combination is an effective and well tolerated regimen for the treatment of advanced colorectal cancer. Its ease of administration and patient tolerance warrant further investigation as an alternative to fluoropyrimidine-based regimens with repeated and prolonged fluorouracil infusions.

Cisplatin, epirubicin and cyclophosphamide (PEC) in the treatment of advanced ovarian cancer.

We report the long-term results of a series of patients affected by advanced epithelial ovarian cancer treated with the PEC combination (cisplatin 60 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 750 mg/m2, all at day 1, every 21 days). Response was evaluated after three cycles, and treatment continued in responsive patients. A total of 80 patients with a median follow-up of 55 months were studied. Fifty-eight patients with stage III ovarian cancer and 22 patients with stage IV received PEC as primary treatment (41 patients), or for residual disease after surgery (37 patients), or for relapsed disease after primary surgery (2 patients). The overall response rate was 67.5% (20.0% complete response, 47.5% partial response), with 22.5% stable disease and 3.7% progressive disease. Median progression free survival was 13.0 months, and median survival was 25 months. Grade III-IV toxicity was moderate: leukopenia 20.0% of patients, thrombocytopenia 5.0%, anemia 16.2%. No cardiac toxicity was observed. In conclusion, the PEC combination, an anthracycline-containing platinum-based regimen, proved to be effective in advanced ovarian cancer, in terms of response rate and overall survival. The regimen was devoid of significant toxicity and in particular of cardiac toxicity.

A phase II study of interferon alpha and low-dose subcutaneous interleukin-2 in advanced renal cell carcinoma.

The activity of the drugs employed in the treatment of metastatic renal cell carcinoma, including biological response modifiers, is limited; one of the aims of clinical research in this area is to maintain the benefits of treatment whilst reducing its toxicity to a minimum level. We have evaluated toxicity and response of the combined administration of recombinant interferon alpha (IFN alpha) and low-dose subcutaneous (s.c.) recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma. A group of 20 previously untreated patients with advanced renal cell carcinoma were included in the study. Treatment consisted of 3 MU/m2 recombinant IFN alpha daily i.m. continuously, and 0.5 MU/m2 recombinant IL-2 twice a day s.c. on days 1-5 for the first week, followed by 1 MU/m2 twice a day for 5 days in the following weeks. For IL-2, a 1-week rest was allowed after 4 weeks of treatment. Response was assessed after 3 months of therapy. Three objective responses were seen, one complete and two partial. Eight patients had stable disease. The median time to progression was 6 months; the median survival for all patients was 14 months. Side-effects were low, limited to grades 1 and 2 in the majority of patients, and included fever, anemia, leukopenia, dyspnea, and abnormalities of liver and renal function tests. Any flu-like syndrome was judged moderate in most patients; however, one-third of the patients refused treatment mostly because of the flu-like syndrome. One of these was the patient experiencing a complete response, who virtually received IFN alpha alone. This regimen, similar to others employed in the treatment of advanced renal cell carcinoma, produced a 15% response rate (95% confidence interval, 0-31%) with 14 months median survival, moderate toxicity and low cost, and required no hospitalization. These data seem to indicate an effectiveness comparable to, and a toxicity lower than, that of regimens employing higher doses of IL-2.

Assessing quality of life in patients with cancer: a comparison of a visual-analogue and a categorical model.

A simple instrument for self-assessment of quality of life (QL) in patients with cancer was elaborated using a linear analogue scale (LAS). The instrument was based on five questions, exploring different functional areas; the same questions were also addressed in a parallel format, where problems were seen from an opposite point of view (positive/negative). The LAS was given to 222 patients, for a total of 372 tests collected. Internal consistency was satisfactory (Cronbach's alpha = 0.75); QL score was significantly correlated to parameters of disease. Concordance between scales, as judged by comparison of parallel formats, was statistically significant but poor. A questionnaire was then elaborated with similar items, based on a categorical scale. A direct comparison between LAS and our questionnaire was made on a group of 41 patients. Internal consistency was poor for the LAS (alpha = 0.58) and good for the questionnaire (alpha = 0.93); Spearman's rank correlation coefficients were disappointing for the LAS and good for the questionnaire; the questionnaire was judged reliable in 82.9% of cases, the LAS in 29.3% only; the questionnaire score, and not the LAS score, was significantly correlated with PS and disease status. In conclusion, many patients appeared unable to correctly interpret the visual-analogue scale; the categorical scale was more immediate and correctly understood by the large majority of patients; the correlation between score and important parameters of QL was maintained, and internal consistency was excellent, indicating a satisfactory reliability of this instrument.

The clinical impact of FEM regimen (5-fluorouracil, 4-epidoxorubicin and mitomycin-C) in advanced gastric cancer patients.

The activity of FEM regimen in metastatic gastric cancer patients was assessed in seventy-seven patients receiving, as palliative treatment, 5FU 600 mg/m2 i.v. on days 1, 8, 29, 36; epiADR 70 mg/m2 i.v. on days 1, 29; MIT-C 10 mg/m2 i.v. on days 1, 29. Cycles were repeated every 58 days. One patient achieved a complete response and 12 a partial response, resulting in an overall response rate of 16% (95% CI: 8% to 24%). Median remission duration was 6 months. Median survival time for all patients was 8 months. Side-effects were mild and principally in the form of leukopenia (three episodes grade III). Our results support the recent findings about the lack of effectiveness of this regimen. Although it is a safe and well tolerable chemotherapeutic combination, FEM regimen should not be recommended as routinary treatment for gastric cancer patients who are not eligible for clinical trials.

[Bullous muco-synechial dermatitis atrophicans. Development and current nosological status]. / Dermatitis ampollar mucosinequiante y atrofiante. Evolución y ubicación nosológica actual.

The authors report six cases of cicatricial pemphigoid emphasizing the initial sintoms and signs of the disease and its ocular localization in order to make an early diagnosis and an efficient therapeutic control; so as to avoid the cicatricial complications. From the therapeutical point of view me propose the use of local therapy and permanent contact lenses.

Dermatitis ampollar mucosinequiante y atrofiante. Evolucion y ubicacion nosologica actual. / Cicatricial pemphigoid. Course and current nosological localization

El motivo de nuestra comunicacion es destacar los primeros sintomas y signos de esta afeccion, con localizacion exclusiva ocular. Todo ello no solo nos facilitaria el diagnostico precoz y el control terapeutico eficaz sino que ademas demoraria o evitaria la formacion de bridas y otras complicaciones. El tratamiento inespecifico local y la protesis ocular por lentes de contacto permanentes cumplirian en parte nuestro proposito

Dermatitis ampollar mucosinequiante y atrofiante. Evolucion y ubicacion nosologica actual. / Cicatricial pemphigoid. Course and current nosological localization

El motivo de nuestra comunicacion es destacar los primeros sintomas y signos de esta afeccion, con localizacion exclusiva ocular. Todo ello no solo nos facilitaria el diagnostico precoz y el control terapeutico eficaz sino que ademas demoraria o evitaria la formacion de bridas y otras complicaciones. El tratamiento inespecifico local y la protesis ocular por lentes de contacto permanentes cumplirian en parte nuestro proposito

Hiperplasia angiolinfoide con eosinofilia. / Angiolymphoid hyperplasia with eosinophilia

A raiz de dos observaciones de hiperplasia angiolinfoide con eosinofilia (HAE), se realizo un analisis bibliografico senalando las caracteristicas y diferencias lo que creemos que en la actualidad debe designarse como HAE. Se encontraron 16 pacientes con tumores unicos y 26 multiples.El tamano de los mismos oscilo entre 2 mm a 4 cm. Se localizaron en cabeza y cuello de 36 a 39 pacientes con preferencia en region temporal, articular y preauricular.Raramente se rubican en mucosas, tronco y extremidades. Surgen entre la tercera y cuarta decada de la vida y con preferencia en mujeres (75%). El tiempo transcurrido entre la aparicion y consulta en general es de un ano. La histopatologia muestra proliferacion vascular de paredes gruesas, de apariencia venosa, en el endotelio se destacan celulas grandes, pleomorficas sin mitosis que hacen saliencia en la luz del vaso, "verticales", de aparencia epitelial como si se tratara de un hibrido entre la celula endotelial y el histiocito rodeada por una infiltracion linfocitaria (los dos casos observados eran dermicos). En las localizaciones hipodermicas se observan centros germinativos e infiltracion eosinofila. Las lesiones tienden a ser persistentes por meses a anos pudiendo observarse resolucion espontanea. La terapeutica de eleccion es la quirurgica

Hiperplasia angiolinfoide con eosinofilia. / Angiolymphoid hyperplasia with eosinophilia

A raiz de dos observaciones de hiperplasia angiolinfoide con eosinofilia (HAE), se realizo un analisis bibliografico senalando las caracteristicas y diferencias lo que creemos que en la actualidad debe designarse como HAE. Se encontraron 16 pacientes con tumores unicos y 26 multiples.El tamano de los mismos oscilo entre 2 mm a 4 cm. Se localizaron en cabeza y cuello de 36 a 39 pacientes con preferencia en region temporal, articular y preauricular.Raramente se rubican en mucosas, tronco y extremidades. Surgen entre la tercera y cuarta decada de la vida y con preferencia en mujeres (75%). El tiempo transcurrido entre la aparicion y consulta en general es de un ano. La histopatologia muestra proliferacion vascular de paredes gruesas, de apariencia venosa, en el endotelio se destacan celulas grandes, pleomorficas sin mitosis que hacen saliencia en la luz del vaso, "verticales", de aparencia epitelial como si se tratara de un hibrido entre la celula endotelial y el histiocito rodeada por una infiltracion linfocitaria (los dos casos observados eran dermicos). En las localizaciones hipodermicas se observan centros germinativos e infiltracion eosinofila. Las lesiones tienden a ser persistentes por meses a anos pudiendo observarse resolucion espontanea. La terapeutica de eleccion es la quirurgica

Dermatitis ampollar mucosinequiante y atrofiante. Hallazgos clinicos, histopatologicos e inmunologicos. / Mucous and atrophying bullous dermatitis. Clinical histopathological and immunological findings

Se comunican dos casos de dermatitis ampollar mucosinequiante y atrofiante (penfigoide cicatrizal). Una de las pacientes estudiadas comienza y evoluciona durante 1 ano con lesiones exclusivamente cutaneas que conducen al diagnostico de penfigoide ampollar. Posteriormente aparece el tipico compromiso mucoso. En el segundo caso, el comienzo fue cutaneo-mucoso. La histologia y la inmunofluorescencia directa e indirecta, corresponden al diagnostico de penfigoide cicatrizal. Los hallazgos en estos casos y la bibliografia consultada, muestran al penfigoide cicatrizal y al ampollar como un mismo proceso patologico, con diferencias clinicas, evolutivas y pronosticas. Se actualiza, ademas, la frecuencia y evolucion de las localizaciones en piel y mucosas, las observaciones al microscopio electronico, los diagnosticos diferenciales mas destacados y las diferentes terapeuticas propuestas, para el control de esta entidad cronica, rebelde y recidivante

Dermatitis ampollar mucosinequiante y atrofiante. Hallazgos clinicos, histopatologicos e inmunologicos. / Mucous and atrophying bullous dermatitis. Clinical histopathological and immunological findings

Se comunican dos casos de dermatitis ampollar mucosinequiante y atrofiante (penfigoide cicatrizal). Una de las pacientes estudiadas comienza y evoluciona durante 1 ano con lesiones exclusivamente cutaneas que conducen al diagnostico de penfigoide ampollar. Posteriormente aparece el tipico compromiso mucoso. En el segundo caso, el comienzo fue cutaneo-mucoso. La histologia y la inmunofluorescencia directa e indirecta, corresponden al diagnostico de penfigoide cicatrizal. Los hallazgos en estos casos y la bibliografia consultada, muestran al penfigoide cicatrizal y al ampollar como un mismo proceso patologico, con diferencias clinicas, evolutivas y pronosticas. Se actualiza, ademas, la frecuencia y evolucion de las localizaciones en piel y mucosas, las observaciones al microscopio electronico, los diagnosticos diferenciales mas destacados y las diferentes terapeuticas propuestas, para el control de esta entidad cronica, rebelde y recidivante