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Publications (4)18.02 Total impact

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    ABSTRACT: We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents. An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model. Median and progression-free survival (prognostic factors) for the whole cohort was 12.6 and 2 months, respectively. Prognostic features associated with shorter survival on multivariate analysis were the number of metastatic sites (greater than 1), time from nephrectomy to metastatic disease (less than 2 years), high alkaline phosphatase, abnormal corrected serum Ca and high lactate dehydrogenase (greater than 1.5 x the upper limit of normal). Four prognostic subgroups were identified by counting the number of adverse prognostic factors. Median survival in patients with zero adverse prognostic factors was 15.6 months compared to 11.7 months in patients with 1, 8.5 months in patients with 2 and 3.5 months in patients with 3 or more. We identified 4 risk groups to predict survival in previously treated patients with renal cell carcinoma. This model was based on data from what is to our knowledge the largest experience in this population. It should be used in clinical trial design, risk stratification and patient counseling.
    The Journal of Urology 12/2007; 178(5):1901-5. · 3.70 Impact Factor
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    ABSTRACT: AE-941 (Neovastat), an antiangiogenic component extracted from cartilage, selectively competes for the binding of vascular endothelial growth factor to its receptor, inhibits matrix metalloproteinases, stimulates tissue plasminogen activator enzymatic activities, and induces apoptotic activities in endothelial cells. A phase I/II study was conducted to obtain information on its safety and efficacy in patients with advanced cancer refractory to treatment or for which no standard treatments were available. Eighty patients with histologically confirmed lung cancer were enrolled in a multicenter, open-label, dose-escalation study of AE-941 (30, 60, 120, or 240 mL/day) administered orally b.i.d. as monotherapy. No dose-limiting toxicity was reported. The most frequent adverse events were nausea (9%), pruritus (5%), anorexia (4%), and vomiting (4%). All adverse events were grade 1/2 except grade 3 constipation (n = 1). A survival analysis was conducted in the 48 patients with unresectable stage IIIA, IIIB, or IV non-small-cell lung cancer. A significant survival advantage was observed for patients receiving doses > 2.6 mL/kg/day (which correspond to approximately 180 mL/day in a 70-kg patient) compared to patients receiving lower doses (median, 6.1 months vs. 4.6 months; P = 0.026). No tumor responses were observed. On the other hand, 26% of the patients in the high-dose group had stable disease compared to 14% in the low-dose group. AE-941 is well tolerated in patients with advanced lung cancer. The higher dose of AE-941 explored in this phase I/II trial may confer a survival benefit.
    Clinical Lung Cancer 02/2003; 4(4):231-6. · 2.04 Impact Factor
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    ABSTRACT: There is considerable evidence to support an immunopathogenic basis of psoriasis. However, changes such as altered angiogenesis have also been implicated in the pathogenesis of psoriasis. AE-941 (Neovastat; Aeterna Laboratories, Quebec City Quebec, Canada) is a naturally occurring product currently in clinical investigation that blocks two main mechanisms of angiogenesis activation, namely, vascular endothelial growth factor and matrix metalloproteinase. We hypothesized that psoriasis could be modulated by inhibiting the neovascularization of psoriatic plaques. We conducted a randomized dose-comparison trial to evaluate the safety and potential therapeutic benefit of AE-941, administered orally to patients with psoriasis. Forty-nine patients with psoriasis were enrolled and assigned to receive AE-941 at 30, 60, 120, or 240 mL/d for 12 weeks. Patients were followed up for another 12-week period. Improvement in the Psoriasis Area and Severity Index (PASI) score was observed in 50%, 41.7%, and 30.8% of the patients receiving 240, 120, and 60 mL/d, respectively. No patients receiving a dosage 30 mL/d showed a PASI score improvement. A statistically significant improvement with increasing dose was observed for the PASI score, severity of itch, and the physician's global assessment. The most commonly reported nonserious drug-related adverse events affected the gastrointestinal system in 12 of 49 patients (primarily nausea, diarrhea, vomiting, flatulence, and constipation) and the skin and appendages in 4 of 49 patients (primarily acne and rash). This randomized phase I/II study provides evidence that the antiangiogenic agent AE-941 offers a new therapeutic approach to the management of psoriasis.
    Journal of the American Academy of Dermatology 11/2002; 47(4):535-41. · 4.91 Impact Factor
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    ABSTRACT: renal cell carcinoma (RCC) is a potential target for anti-angiogenic drugs because of its high vascularization. Neovastat (AE-941) is an inhibitor of angiogenesis with a mechanism of action that could prove beneficial in the treatment of RCC. Patients and design A phase II trial was conducted to identify the long-term safety profile of Neovastat in advanced cancer patients and to obtain preliminary information on its efficacy in solid tumors refractory to standard treatments. Neovastat (60 or 240 ml/day) was administered orally (b.i.d.) to 144 patients with solid tumors refractory to standard therapies or for whom no standard treatments were available. A survival analysis was conducted on 22 patients with a primary diagnosis of refractory RCC to determine whether the dose of Neovastat had any effect. A significant relationship between dose and survival was observed; the median survival time was significantly longer (16.3 versus 7.1 months; P = 0.01) in patients treated with Neovastat 240 ml/day (n = 14) compared with patients receiving 60 ml/day (n = 8). No dose-limiting toxicity was reported. The most frequent adverse event was taste alteration (13.6%). Neovastat is well tolerated by advanced cancer patients at doses of 60 and 240 ml/day. The higher dose of Neovastat administered in this trial is associated with a survival benefit in RCC, which is not explained by differences in major prognostic factors.
    Annals of Oncology 09/2002; 13(8):1259-63. · 7.38 Impact Factor