Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) which have a combined incidence of 5–8/100,000 population, represent the most common primary central nervous system tumors. The treatment outcomes even with aggressive approach including surgery, radiaton therapy and chemotherapy are dismal with median reported survival is less than 1 year. Temozolomide is a new drug which has shown promise in treating malignant gliomas and other difficult-to-treat tumors. This drug is a per os (p.o) imidazotetrazine second-generation alkylating agent which represents the leading compound in a new class of chemotherapeutic agents that enter the cerebrospinal fluid and do not require hepatic metabolism for activation. The efficacy of temozolomide was tested in vitro studies and has demonstrated schedule-dependent antitumor activity against highly resistant malignancies, including high-grade glioma (HGG). In addition, in clinical studies, temozolomide consistently demonstrates reproducible linear pharmacokinetics with approximately 100% p.o. bioavailability, noncumulative minimal myelosuppression that is rapidly reversible, and activity against a variety of solid tumors in both children and adults. Moreover, preclinical studies have evaluated the combination of temozolomide with other alkylating agents and inhibitors of the DNA repair protein O6-alkylguanine alkyltransferase to overcome resistance to chemotherapy in malignant glioma and malignant metastatic melanoma. At the present time temozolomide is approved in the United States for the treatment of adult patients with refractory anaplastic astrocytoma and, in the European Union, for treatment of glioblastoma multiforme showing progression or recurrence after standard therapy. Temozolomide’s characteristics which make it a candidate for a wide range of clinical testing to evaluate the potential of combination treatments in different tumor types are its predictable bioavailability and minimal toxicity. An overview of the mechanism of action of temozolomide and a summary of results from more important randomized controlled clinical trials in high grade gliomas are presented here.
The effectiveness of radiotherapy in patients with basal cell carcinoma (BCC) has been already reported in the literature. However, there is little information about the irradiation of BCC in elderly patients, especially due to the low conformity of them to daily irradiation. Thirty-eight retrospectively selected elderly patients (78 years as median age) diagnosed with skin BCC of the head and neck area were treated with five weekly fractions of 600 cGy by three-dimensional conformal radiotherapy (3DCRT) as an adjuvant treatment. The primary endpoint was the relapse free survival. Acute toxicity, as secondary endpoint, was assessed according to EORTC/RTOG criteria. Among our patients, there were only three local recurrences at 15, 32 and 38 months post-3DCRT. There was no severe toxicity, while only 10 out of 38 patients presented grade II/III skin toxicity. Our proposed irradiation schedule seems effective in terms of local control and acute toxicity and could be an alternative scheme for elderly patients unfit for daily irradiation.
Introduction: The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients. Methods: 3 irradiation schedules were analyzed: 48.30 Gy in 21 fractions (group A, n = 60), 42.56 Gy in 16 fractions (group B, n = 27) and 50 Gy in 25 fractions (group C, n = 30) of the front chest wall. All groups were also treated with a supraclavicular field, with 39.10 Gy in 17 fractions (group A), 37.24 Gy in 14 fractions (group B) or 45 Gy in 25 fractions (group C). Results: No local recurrences were noted in any group during 36 months of follow-up. Acute skin toxicity presented in all groups, with 58.3%, 70.4% and 60% of grade I; 35%, 25.9% and 40% of grade II; 6.7%, 3.7% and 0% of grade III being seen in groups A, B and C, respectively. Late skin toxicity was noted only as grade I in 16.7%, 25.9% and 26.7% of groups A, B and C, respectively. No significant difference was noted among all groups for either acute or late skin toxicity, or for radio-pneumonitis (chi2 test, p > 0.05). Conclusion: All schedules were equally effective with equivalent toxicity. A prospective randomized study is needed to confirm our results.
Purpose. The purpose is to evaluate the feasibility, efficacy, and the toxicity of three-dimensional conformal radiotherapy (3DCRT) in patients with advanced hepatocelluar carcinoma (HCC) and inferior vena cava tumor thrombosis (IVCTT). Methods. Between 2007 and 2012, in a retrospective way, 9 patients (median age 69 years) with advanced HCC and IVCTT unfit for surgery, radiofrequency ablation, embolization, or chemotherapy were treated with three-dimensional conformal radiotherapy (3DCRT). The radiotherapy volume included both primary tumor and IVTT. The radiotherapy schedule was 50–52 Gy in 2 Gy fractions. Overall survival (OS), response to radiotherapy, visual analogue scale (VAS), and toxicity were assessed. Results. All patients demonstrated a response rate up to 60%. During radiotherapy, 3 patients experienced grade 1 nausea/vomit toxicity. All patients demonstrated an elevation of the liver enzymes (3 patients with grade 1 and 6 patients with grade 2). The mean VAS-score was decreased from 6.11 to 3.11, while the median overall survival was 24 months. Conclusion. 3DCRT achieves a very high local control rate and is suitable for patients with HCC and IVTT, while the documented radiation induced toxicity is moderate. It can be recommended for palliation in patients unable to undergo curative therapies.
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