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Prognostic factors such as surgery and pathology in vulvar squamous cell carcinoma are studied.47 patients with vulva squamous cell carcinoma treated at the Gynecology Department of the University of Padua, have been retrospectively studied.At the univariate relapse-free survival analysis, a significant association was found for histological grade, stage of disease and type of surgery. All patients presented vulvar squamous cell carcinoma: G(1) in 25 (53%), G(2) in 14 (30%), and G(3) in 8 (17%) patients. The distribution of stages was as following: stage 1 in 6 (13%), stage 2 in 20 (43%), stage 3 in 11 (23%), and stage 4 in 10 patients (21%). Radiotherapy was performed in 13 patients. Among the 47 patients evaluable: 26 (55.3%) developed local recurrence, 12 of these patients developed a second local relapse, 3 of these also had distant metastases (lung in 1 patient, lomboaortic and mediastinic lymph nodes in the other 2 patients). Stromal invasions wereor=9 mm in 14 patients with 6 relapses and9 mm in 30 patients with 27 relapses (univariated analysis p=0 0066). Five episodes (10,6%) of thrombosis were observed.After multivariate analysis, surgery, stage and stromal invasion over 9 mm (hazard ratio=3.1; 95% confidence interval: 1.3-7.7) proved to be the most dominant predictor for relapse-free survival. Histological grades 1 and 2 were predictive of better disease-free survival (p=0.0012).

There is pre-clinical evidence of synergism between cisplatin and temozolomide due to higher inhibition of O(6)-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system and in the mechanisms of drug resistance to alkylating agents.Heavily pre-treated patients with temozolomide-refractory high-grade malignant glioma received cisplatin at a dose of 75 mg/m(2) on day 1 and temozolomide at a dose of 150 mg/m(2) on days 1 to 5 every 21 days until progression or major toxicity.Twenty-four patients were enrolled and a total of 96 cycles were delivered (median for each patient=4). Toxicity was manageable and mostly grade 1-2: haematological, gastroenterological (nausea and vomiting) and fatigue. In patients with glioblastoma, an overall response rate of 29.4% was achieved, with no complete response, and with a disease control rate (responses plus stabilizations) of 64.7%. The median time to progression was 3.8 months (95% confidence interval 2.4-6.8), progression-free survival at 6 months was 28% and overall survival was 7.0 months (95% confidence interval 4.8-11.0).The combination of temozolomide and cisplatin is safe and moderately effective in the treatment of heavily pre-treated patients with relapsed high-grade glioma refractory to single-agent temozolomide.

Advanced renal cancer remains a challenge for oncologists since no treatment other than surgery has demonstrated a clear survival advantage.Gemcitabine was given to suitable patients at a fixed infusion rate of 10 mg/m2/min. Eighteen patients received concomitant immunotherapy, mostly low doses of interleukin 2 (IL2).Thirty patients were enrolled. The overall response rate was 14% (22% in the subset of patients treated with both chemotherapy and immunotherapy) with a median progression-free survival time of 4.1 + months. Toxicity was not mild, mostly fatigue, nausea and anaemia, even though not life threatening.Gemcitabine at the fixed infusion rate of 10 mg/m2/min with concomitant low doses of IL2 could be useful in the palliative treatment of symptomatic patients with renal carcinoma progressing after tyrosine kinases inhibitor.

There is pre-clinical evidence of synergism between cisplatin (P) and temozolomide (T) due to higher inhibition by T of O6-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system. T and P are active against malignant gliomas while thalidomide (TH) is emerging as an inhibitor of angiogenesis.Triplets of patients with malignant brain tumors received escalating doses of P, T and TH up to the dose-limiting-toxicity (DLT) and the maximal tolerated dose (MTD).Seventeen patients were enrolled and a total of 74 cycles were delivered. The MTD was P 75 mg/m2 day 1 and T 150 mg/m2 days 1 to 5 every 21 days with a concomitant 200 mg total daily dose of TH. DLT events were G4 thrombocytopenia and febrile neutropenia.Concomitant administration of P 75 mg/m2 day 1, T 150 mg/m2 days 1 to 5 every 21 days and concomitant TH at a total daily dose of 150 mg is feasible and safe. Early efficacy data are encouraging and a phase II study is ongoing.