Phase I study of temozolomide and lomustine in the treatment of high grade malignant glioma.

Systematic reviews and meta-analysis have demonstrated an improved prognosis by chemotherapy of malignant glioma patients. The effects of clinical research therefore have the aim to find more active drugs or new combination therapies. The combination of Temozolomide (TMZ) and nitrosoureas was evaluated preclinically with an evidence of therapeutic synergy. Based on these findings, we have carried out a phase I study with TMZ administered in low, prolonged doses of 75 mg/m2 per day, once a day for 21 days, escalated in cohorts of 3 patients, in combination with a fixed dose of Lomustine (CCNU) 100 mg/m2 orally on day 1. MTD was evident. The treatment was generally well tolerated. We did not observe bleeding or severe infections, as described for several combination chemotherapies with TMZ and other agents. In this study, for the first time in high grade malignant glioma, two orally administrated drugs were associated .TMZ 75 mg/m2 for 28 consecutive days and CCNU 100 mg/m2 on day 1 of every 6 weeks could be recommended as a safe treatment dosage. One of the ten patients evaluated for clinical response showed a partial response, while nine showed stability of disease, with a median duration of from 5 to 6 months.

Real-time contrast-enhanced specific ultrasound in staging and follow-up of splenic lymphomas.

From January 2003 to April 2005 we studied 25 lymphoma patients (10 with HD, 4 with low-grade NHL, 6 with high-grade NHL and 5 with chronic lymphatic leukaemia; 14 men, 11 women, age range 28-79 years). After a baseline US study we rapidly injected 4.8 mL of the second-generation microbubble contrast agent SonoVue (Bracco, Italy). Contrast enhanced studies were carried out with the contrast-specific software named Contrast Tuned Imaging (Esaote, Italy) using a continuous, harmonic acquisition and a low acoustic pressure. The CS-US findings were correlated with results of standard tools, including CT, MRI, US follow up. CS-US revealed correctly 47 out of the 52 lesions identified by CT scan, in the absence of false positive findings (sensitivity = 90%; Specificity = 100%, in comparison to CT scan). Complete concordance in evaluating the lesion extension of the CS-US in respect to CT was 88%, while underestimate occurred in 9% and overestimate in 3% of cases. On the contrary, basic sonography defined correctly the dimensional alteration in 52% of the cases, underestimated in 35% and overestimated in 13%, thus showing significantly lower accuracy (chi-square = 30.0, p < 0.001). In our experience, CS-US was superior to conventional sonography even from a qualitative point of view.

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience.

In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate first-line treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (<18 years, 36 of 42=85.7%; >or=18 years, 41 of 48=85.4%, P=not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P=.018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial.