6533b7d0fe1ef96bd125b765

RESEARCH PRODUCT

Efficacy of weekly low-dose chemotherapy in elderly women with advanced ovarian cancer: is there an antiangiogenic effect?

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13133 Background: In elderly patients decreased functionality of multiple organ systems may affect pharmacokinetics and pharmacodynamics of drugs. For this reason elderly cancer patients experience enhanced susceptibility to common chemotherapy-related adverse events. A way to prevent these effects could be metronomic chemotherapy, which is a variation of dose-dense therapy, with a cumulative dose significantly lower than maximum tolerated dose. Methods: 27 advanced ovarian cancer patients, median age 67 (range 60–86), received low dose weekly continuous chemotherapy until disease progression. All patients were treated with CBDCA AUC 2 mg/ml/min and Docetaxel 35 mg/sqm (adjusted according with Kintzel & Dorr formula) i.v. weekly. Primary endpoints were response rate (RR) and time to treatment failure (TTF). Moreover we considered as secondary endpoints toxicity profile, VEGF values and Quality of Life (QoL) score. RR and TTF were evaluated with RECIST criteria and Kaplan-Meyer formula respectively, toxicity was assessed according to the NCI-CTC. VEGF concentrations were analyzed by ELISA, QoL score was determined using the ADL/IADL and EORTC QLQ-C30 questionnaires, at baseline (T0) and at the end of therapy (T1). Results: median duration of treatment was 39 weeks. 2 Complete Responses (CR) and 5 Partial Responses (PR) were achieved for a 26% RR. Stable Disease was achieved in 18 pts (67%) with a total Clinical Benefit (CB) of 93%. Overall toxicity was very low: haematological G1/2 - 6 pts; gastrointestinal G1 - 8 pts; neurological G1/2 - 5 pts; cutaneous G3 - 1 pt; renal G1 - 1 pt. A mean TTF of 17.4 months was reached. Mean VEGF values (T0): 527 ± 35 pg/ml, (T1): 335 ± 18 pg/ml (p = 0,003). QoL score (T0): 45.2 ± 12, (T1): 47.5 ± 25 (p = 0,06). Conclusions: first results seem to be very encouraging, even if the number of responses is too small and we need to enrol more pts to reach a good statistical evaluation. Nevertheless the use of this “metronomic” schedule shows that VEGF values decrease strongly during the treatment and is maintained also when treatment is discontinued. Thus it suggests a preminent antiangiogenic role of this schedule according with the most recent preclinical and clinical studies. No significant financial relationships to disclose.