ABSTRACT
OBJECTIVE: Temozolomide is a novel oral alkylating agent, active against metastatic melanoma. Combinations of chemotherapy and biological response modifiers have been associated with increased antitumour activity. A multicentre phase II study was performed to assess the activity and toxicity of temozolomide in combination with interferon alpha-2b. PATIENTS AND METHODS: Eligible patients had histologically confirmed metastatic melanoma. Previously untreated patients received temozolomide administered orally at a dose of 150 mg/m/day for 5 days every 4 weeks, in combination with interferon given continuously subcutaneously twice a week at a dose of 10 MU/m. Treatment continued until disease progression or for a maximum of 12 months. RESULTS: From June 1999 to August 2002, 27 eligible patients were included in the study at six centres. Median age was 59 (28-77) years; 17 male and 10 female patients were recruited; the median Karnofsky performance score was 90 (70-100); three patients had received prior adjuvant interferon; the majority of patients had fewer than three involved sites. A total of 96 cycles were administered; there were one complete response, four partial response and five stable disease (overall response rate: 18.5%, 95% confidence interval: 6.3-38.1). All responses were seen in patients with exclusively lymph node and pulmonary disease [M1a (one patient); M1b (four patients)]. The median response duration was 6.9 months. One patient remains in complete remission at 4 years. The median time to progression and the median survival were 1.87 and 9.5 months, respectively. Haematological toxicity was neutropenia G-IV: 1, G-III: 4, thrombocytopenia G-III: 2, and anaemia G-III: 2. Predominant non-haematological toxicity was hepatotoxicity G-III: 4. Other toxicities were mild or moderate. Dose reduction was required for nine cycles of interferon, one of temozolomide and two of both drugs. CONCLUSIONS: Temozolomide in combination with interferon is a well-tolerated palliative regimen that has moderate activity against metastatic melanoma. Further evaluation of this regimen in comparative studies or in combination with other drugs is warranted.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Female , Humans , Immunologic Factors/therapeutic use , Interferon alpha-2 , Interferon-alpha/administration & dosage , Male , Maximum Tolerated Dose , Melanoma/secondary , Middle Aged , Neoplasm Staging , Recombinant Proteins , Skin Neoplasms/pathology , Survival Rate , TemozolomideABSTRACT
Toxic epidermal necrolysis (TEN) is an infrequent disease but with a high mortality rate. It is a mucocutaneous reaction resulting from hypersensitivity to a variety of agents including most anticonvulsants. Many patients with primary or metastatic intracranial tumours receive anticonvulsants for seizure prophylaxis despite their efficacy not having been clearly demonstrated. Moreover, several cases have been reported in the literature in which serious adverse drug reactions such as TEN and Stevens-Johnson syndrome (SJS) have occurred following anticonvulsants exposure. In some of these cases the effect of radiation therapy and the tapering of steroid dose on the pathogenesis of these reactions have been highlighted. We report, here, a case of TEN that appeared in a patient receiving phenytoin, and shortly after the end of cranial and thoracic irradiation therapy for brain metastases of non-small cell lung cancer. Clinical considerations about diagnosis of SJS and TEN are presented. The use of prophylactic anticonvulsants is also discussed as well as a review of the literature.
Subject(s)
Anticonvulsants/adverse effects , Cranial Irradiation/adverse effects , Phenytoin/adverse effects , Stevens-Johnson Syndrome/etiology , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Non-Small-Cell Lung/therapy , Humans , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Stevens-Johnson Syndrome/diagnosisABSTRACT
Introducción. El objetivo del presente estudio es valorar los resultados obtenidos con la aplicación de la técnica de biopsia selectiva de ganglio centinela (BSGC) en el tratamiento del melanoma. Pacientes y método. Estudio clínico prospectivo. Se practicó BSGC a los melanomas primarios con espesor de Breslow mayor de 1 mm, o factores de mal pronóstico asociados. Desde marzo de 2000 a diciembre de 2001 se valoraron 53 melanomas. Resultados. Se realizó BSGC en 37 casos, el 69,8 por ciento de los melanomas. Se obtuvieron 36 mapas linfáticos (97,3 por ciento de las gammagrafías efectuadas) y se practicaron 45 biopsias ganglionares, debido a que en 9 casos (25 por ciento) se obtuvo drenaje a dos territorios. Se obtuvieron metástasis en el ganglio centinela en tres pacientes (8,3 por ciento). En estos casos se realizó linfadenectomía regional, en dos de ellos se halló afección en el resto de la cadena, y en el tercer caso el centinela era el único ganglio afectado. Conclusiones. El 8,3 por ciento de los pacientes a los que se detectó afección metastásica ganglionar se benefició del tratamiento complementario, lo que unido a la casi nula morbilidad hace que la BSGC sea una técnica que debería ser estandarizada en todos los centros donde sea realizable y que atiendan esta patología. (AU)
