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.

Microwave heating should be over 44 °C for favourable treatment response, when combined with radiotherapy. More patients are needed to confirm the above results.

Radiotherapy (R/T) is frequently used for palliative treatment of painful bone metastases; however, complete alleviation of pain is not always achieved. This study was designed to evaluate pain management outcomes and quality of life (QoL) measures in cancer patients with metastatic bone pain receiving a combination of R/T and either transdermal therapeutic fentanyl (TTS-F) patches or codeine/paracetamol.A total of 460 palliative care patients with bone metastases who received R/T were enrolled in this prospective, open-label study. The patients were randomized to initially receive a total dose of 120 mg codeine/paracetamol per day or TTS-F patches releasing 25 μg fentanyl per hour. Pain measures were assessed on the basis of selected questions from the Greek-Brief Pain Inventory. Overall treatment satisfaction (scale, 1 to 4), QoL, and European Collaborative Oncology Group status were also recorded.Among the 460 patients, 422 were eligible for evaluation. Pain measures in the TTS-F group demonstrated statistically significant improvements during the study that were superior to those in the codeine/paracetamol group (p < 0.05). Likewise, there was a significantly greater increase (p < 0.05) in the mean satisfaction score for patients in TTS-F group at every visit between baseline and month two. The vast majority (95.8 percent) of patients in the codeine/paracetamol group increased their medication dosage until the end of the study, whereas in the TTS-F group the respective percentage was only 6.1. Both treatments were generally well tolerated, with constipation as the most common side effect followed by sleep disturbances and nausea. The overall frequencies of side effects were higher in the codeine/paracetamol group.The results therefore indicate that TTS-F offers more effective pain relief than codeine/paracetamol, in combination with R/T, in patients with metastatic bone pain, obtaining complete treatment satisfaction matched by improvements in their QoL.