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.
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.
10651 Background: We designed a phase I-II trial to determine the combination dose of liposomal doxorubicin (Myocet) plus gemcitabine (Gemzar), and to evaluate the safety and feasibility of the regimen Methods: Patients with histologically confirmed breast cancer, untreated distant metastasis, age >18 years old, left ventricular ejection fraction (LVEF) >50% and adequate bone marrow, renal and hepatic function were included in the study. Patients received up to six cycles of treatment. No G-CSF support was used prophylactically. LVEF was repeated at 3, and 6 months, and every 6 months thereafter. Results: Phase I: After 6 patients, the recommended dose was M (55 mg/m2) D1 and G (900 mg/m2) D1 and 8, administered every 21 days. Phase II: 53 patients have been enrolled; 52 are included in the safety analysis and 42 in the efficacy analysis. The median age of the population was 61 years of age (32–79). ECOG PS was 0 in 55%, 1 in 41%, 2 in 4%. Postmenopausal status in 87%. Main histology was ductal carcinoma (85%). Prior adjuvant anthracyclines had been administered in 19 cases (median dose of doxorubicin: 300 mg/m2, or epirubicin: 425 mg/m2). Metastasic lesions were in liver (25), lung (17), bone (16), and lymph nodes (25). Patients received a median number of 5 cycles (range 1–6). Median relative dose intensity was 83% for M and 75% for G. Grade III-IV hematologic toxicity per administered cycles was: leukopenia (21.9%), neutropenia (31.2%), febrile neutropenia (4 %), and thrombocytopenia (7.4%). Grade III-IV non-hematologic toxicities were stomatitis (4.8%), nausea (1.7%), vomiting (2.2%), asthenia (2.6%) and diarrhea (0.8%). Thirteen of 52 pts (25%) had alopecia grade III-IV. No signs or symptoms of cardiac impairment have been seen. An objective response rate of 62% was obtained (95% CI: 45.6- 76.4%). Two patients had complete response (4.8%), 24 partial response (57.1%), 10 stable disease and 6 progressive disease. The response rate was similar in patients with or without previous adjuvant anthracyclines (68.5% and 61%, respectively). Conclusions: The combination of liposomal doxorubicin plus gemcitabine has high efficacy and low toxicity in advanced breast cancer patients, and may be a valuable option in patients that have received adjuvant anthracyclines. [Table: see text]
1560 Poster Board I-583 Background Hodgkin lymphoma is defined by Reed Stemberg (RS) tumor cells in a microenvironment composed of a deregulated cytokine network and diverse cell populations, associated with their respective extracellular matrix, defining an inflammatory microenvironment. COX-2 (cyclooxygenase 2) is an inflammatory induced enzyme involved in the pathogenesis and prognosis of several solid tumors (colorectal, breast, ovarian, lung, etc). Its role in hematological malignancies is being recognized and specifically its expression in Hodgkin lymphoma has been associated with higher proliferation and angiogenesis. Aim To investigate the prognostic value of COX-2 expression in a large uniformly treated population with Hodgkin lymphoma. Methods We examined tissue microarrays for COX-2 expression in 242 patients of the Hodgkin Lymphoma Spanish Network treated with ABVD with or without Radiotherapy (XRT) according to AA (Ann Arbor) staging. Tissue sections were stained with monoclonal antibodies to COX-2 and the expression was scored and validated by a pathology review. Cox-2 was dichotomized as either negative (no RS staining) or positive. Plots of Kaplan Meier were constructed for survival analysis and most recognized clinical variables (age, sex, presence of bulky disease, B symptoms, AA stage, International prognostic system for Hodgkin lymphoma (IPS), ECOG performance status (PS) were investigated for their prognostic importance along with COX-2 expression by univariate and multivariate analysis. Results Median age was 33 (10 to 83). COX-2 was expressed in 89 pts (37%), 99 pts (41%) presented with AA stage III-IV, 98 pts presented B symptoms (40%) and 124 pts (51%) received XRT added to ABVD chemotherapy, 66% of patients with AA stage I-II and 30% of pts presenting with AA stage III-IV. There were no differences in the distribution of clinical variables according to the COX-2 expression, except for a trend to increased positivity in nodular sclerosis and lymphocyte-depleted subtypes and higher AA stage. With a median follow up for alive patients of 59 months, the PFS at 5 years were 61% and 79% for COX-2 + and negative respectively (p=0.004). OS were 73% and 91% respectively (p<0.001) (Figure). By univariate analysis age higher than 45 years, presence of B symptoms, AA stage III-IV, PS >=2, IPS>2, no XRT treatment and COX-2 expression were associated with an unfavourable PFS and OS. By multivariate analysis only the IPS (HR 3.72) and COX-2 (HR 1.72) expression were independently associated with the outcome. Interestingly the major impact in the prognosis was observed in the favourable AA stage (I-II) and IPS (0-2) groups. In fact in these low risk groups the expression of COX-2 define a group of significant worse prognosis. Accordingly, the 46 patients (32%) of the 143 patients presenting an AA stage of I-II had a PFS at 5 years of 73% versus 86% of those COX-2 negative (p=0.031). Similarly the OS at 5 years of both groups also differ with 82 and 94% for COX + and negative respectively (p=0.004). Conclusion COX-2 is expressed in approximately a third of RS cells and is a major independent unfavourable prognostic factor. Of main relevance is the fact that in the favourable groups of the AA and IPS the expression of COX-2 identify a group of significant worse prognosis that need different approach. According to our data COX-2 can be a major prognostic variable in this disease and potentially could be a therapeutic target. Disclosures No relevant conflicts of interest to declare.
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