A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma.

PURPOSE: To evaluate the maximum tolerated dose of simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) associated with temozolomide in patients with glioblastoma. PATIENTS AND METHODS: Between November 2009 and January 2012, nine patients with malignant glioma were enrolled in this phase I clinical trial. Radiotherapy was delivered using fractions of 2.5Gy on the planning target volume b and of 1.9Gy on the planning target volume a. Volumes were defined as follow: gross tumour volume b: tumour taking up contrast on T1 weighted MRI images; clinical target volume b: gross tumour volume b+0.5cm (adapted to the anatomical structures) and lastly planning target volume b: clinical target volume b+0.5cm; gross tumour volume a: tumour (gross tumour volume b)+2cm and including oedema outlined on T2Flair MRI sequences; clinical target volume a gross tumour volume a+0.5cm (adapted to the anatomical structures); planning target volume a: clinical target volume a+0.5cm. Three patients were enrolled at each of the three levels of dose (70, 75 and 80Gy prescribed on the planning target volume b and 56, 60 and 60.8Gy on the planning target volume a). Radiotherapy was delivered with temozolomide according to the standard protocol. Dose-limiting toxicities were defined as any haematological toxicities at least grade 4 or as any radiotherapy-related non-haematological acute toxicities at least grade 3, according to the Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: Until the last dose level of 80Gy, no patient showed dose-limiting toxicity. CONCLUSIONS: SIB-IMRT, at least until a dose of 80Gy in 32 daily fractions, associated with temozolomide is feasible and well tolerated.

[Image-guided radiotherapy in prostate cancer: concepts and implications]. / Radiothérapie guidée par l'image des cancers prostatiques : concepts et implications.

Intensity modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) are technological developments, which when applied in a model of prostate cancer, led to a significant reduction in the toxicity and digestive and urinary sequelae of 3D conformational radiotherapy. The major clinical benefits of these techniques with regard to reduced digestive and urinary toxicity are unequivocal since very few sequelae have been reported at 10 years (2% of grade 2 and 1% of grade 3 digestive toxicity; 11% of grade 2 and 5% of grade 3 urinary toxicity). Even when these two techniques are combined, IG-IMRT significantly diminishes late genitourinary toxicity. In the absence of adaptive radiotherapy, there are many IGRT protocols and repositioning techniques, and every step in the IGRT process must be carried out with extreme rigor: installing the patient and contention system, repositioning technique with or without fiduciary markers, type of repositioning imaging, definition of margins inherent in each technique (prostate, seminal vesicles and/or pelvic lymph nodes), frequency of repositioning during treatment, dietary constraints with or without rectal lavage. For these reasons, every centre that performs IGRT must carefully and rigorously assess the uncertainties of repositioning linked to the IGRT technique. In this review, we analyzed data from the literature based on dosimetric studies and the proven clinical impact in order to answer the different questions asked by radiation oncologists at every step of the IGRT process for cancer of the prostate. Recommendations are made for the repositioning protocols according to the most widely used repositioning techniques: fiduciary markers or soft tissues, kV-CBCT or MV-CBCT, 3D ultrasonography.

The influence of food on the bioavailability of a slow release theophylline preparation.

Food-induced changes in the absorption of Theostat 300, a controlled release formulation of theophylline, have been studied in healthy volunteers. This open, randomised, 3-way, single-dose study involved 12 volunteers who received the drug either while fasting, or with a standardised low-fat (10g), or high-fat (60g) breakfast. Each subject was studied over a 3-week period, with 3 separate days of oral treatment and a 7-day washout period between treatments. The results showed no differences in AUC0-24 and tmax values between the 3 kinds of diet. The only differences observed concerned absorption. Food intake increased Cmax values by 20%. The steady-state peak concentration obtained by means of simulated plasma levels was not influenced by food intake. This slight food-drug interaction of Theostat 300 seemed to be of no clinical significance.

[Value of a daily dose of theophylline in the treatment of nocturnal asthma]. / Intérêt d'une prise quotidienne de théophylline dans le traitement de l'asthme nocturne.

The authors report the results obtained with one single daily dose of 10 mg/kg of a long-acting theophylline preparation administered in the evening to asthmatic patients previously treated with the same dose twice a day. Twenty-seven patients presenting with airway obstruction reversible by beta-stimulants entered the study; their mean FEV1 value was 57% of the expected value, and diffuse sibilances were present; paroxysmal attacks occasionally occurred, particularly at night. No significant difference was found between the two dosage regimens with regard to symptomatic improvement, adjuvant drug consumption, and plasma theophylline levels 12 hours after the evening dose. The classical side-effects of theophylline therapy were not increased by the once-a-day regimen. It is concluded that one dose of theophylline per day is effective in the treatment of nocturnal asthma.