Vasilis Karavasilis

Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1

BackgroundCancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets.MethodsParaffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data.ResultsVEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1.ConclusionAngiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting.

Pharmacodynamics of non-break weekly paclitaxel (Taxol) and pharmacokinetics of Cremophor-EL vehicle: results of a dose-escalation study.

We characterized the toxicity and determined the maximum tolerated dose of non-break weekly paclitaxel (Taxol) in chemotherapy-naive cancer patients, and studied pharmacokinetics of the formulation vehicle Cremophor-EL with this schedule. Twenty-three patients with primary refractory solid tumors received weekly paclitaxel at the dose range of 70–200 mg/m2. As dose-limiting toxicity we defined granulocytopenia grade ≥2 causing a treatment delay for more than 2 weeks, or febrile neutropenia or grade >2 organ-specific toxicity. Plasma kinetics of Cremophor-EL were analyzed over the first five courses of treatment. Non-break weekly paclitaxel was feasible at doses up to 110 mg/m2, while granulocytopenia precluded scheduled administration of doses ≥130 mg/m2. Clinically relevant peripheral neurotoxicity tended to occur at around 1500 mg/m2 cumulative dosage at weekly doses ≥110 mg/m2. Detectable Cremophor-EL levels were found in all pre-dose samples, but there was no evidence of accumulation up to the sixth course. Our results, discussed in the light of an overview of published data, suggest that chronic weekly administration of paclitaxel is feasible and with a lack of significant accumulation of Cremophor-EL levels at doses up to 90 mg/m2.

Invasive Thymoma: A Clinical Study of 23 Cases

Background: Invasive thymoma is a rare mediastinal tumor. Clinicopathological characteristics that influence survival of patients with this tumor are under debate. Treatment is based on tumor resection. The benefice of therapies, such as radiation therapy (RT) and/or chemotherapy (CT) as adjuvant treatments to surgery, or palliative therapy to unresectable or recurrent thymoma are discussed. Objectives: The aim of this study was to assess patients with invasive thymoma, with specific emphasis on factors predicting survival. Methods: We studied retrospectively 23 patients with invasive thymoma. Parameters assessed were age, presenting symptoms, histological features, stage at diagnosis, treatment modalities and survival. All patients received primary therapy: 11 patients (48%) had tumor resection associated with CT and/or RT, while 12 patients had palliative therapy including RT and/or CT. Regimens for CT were based on cisplatin. Results: Patients’ mean age was 58 years. Three patients had stage II disease at diagnosis (13%), 8 patients had stage III (35%) and 12 patients had stage IV (52%). Median overall survival was 20 months (range: 4–160) and five-year survival rate was 43.5% (10 patients). Surgical resection had a significant impact on survival (p < 0.0001). Survival was also related to stage of the disease at diagnosis (p = 0.006), but not to histology of the tumor (p = 0.12). Salvage treatment was of clinical importance: 5 out of 15 patients (33.3%) who relapsed during a 5-year follow-up responded to a multimodality therapeutic approach that affected survival (p = 0.019). Conclusion: Factors determining the outcome of these tumors are the stage of the disease at diagnosis, and the adequacy of surgical removal. Salvage treatment of recurrent thymoma may give a moderate response rate and improve survival.

Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1–16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4–8.8) and overall survival was 11.9 months (95% confidence interval: 7.4–21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

Salvage treatment of relapsed/refractory small cell lung cancer with pazopanib: A Hellenic Oncology Research Groups (HORG) phase II study.

8561Background: Pazopanib (PZB) is a small anti-angiogenic molecule inhibiting the tyrosine kinase of VEGFR-1, VEGFR-2, VEGFR-3, PDGF, and c-kit. Several studies have shown that angiogenesis is of ...