Phase II study of docetaxel-prednisone (DP) in combination with metronomic cyclophosphamide (CTX) and celecoxib (C) ......

Sub-category: Prostate Cancer

Category: Genitourinary Cancer

Meeting: 2009 ASCO Annual Meeting

Citation: J Clin Oncol 27, 2009 (suppl; abstr e16032)

Abstract No: e16032

Author(s): A. Fontana, G. Bocci, L. Galli, L. Derosa, G. Minuti, M. D'Arcangelo, D. Santini, L. Landi, S. Bursi, A. Falcone; ASL6 and University of Pisa, ITT, Livorno, Italy; University of Pisa, Pisa, Italy; ASL6, ITT, Livorno, Italy; University Campus Bio-Medico, Roma, Italy

Abstract:

Background: Metronomic oral CTX and C has demonstrated activity and a favourable toxicity profile in CRCP. Combination of such strategy with the standard DP could be of interest.

Methods: Pts with CRPC received D 60 mg/sqm iv day 1 every 3 weeks up to 12 cycles and from day 2 continuously: P 5 mg po BID, CTX 50 mg po daily, and C 200 mg po BID. Primary objective is the percentage of pts free of progression at 6 months; secondary are: PSA levels decrease ? 50%, objective responses (RECIST), toxicities (NCI-CTC criteria) survival and pharmacodynamic evaluations.

Results: To date 29 pts have been enrolled. Main pts characteristics are: median age 72 years (52-78 years), median PS 0 (0-2), median baseline PSA level 38,8 ng/mL (2.5-1309 ng/mL); main sites of disease: bone 23 pts (79%), lymphnodes 6 pts (21%), liver 1 pt (3,5%). Twenty-nine pts are evaluable for toxicity whereas 28 for PSA response (1 pt abandoned the study due to allergic reaction after first D administration). Median number of D cycles delivered is 10 (1-12) and median duration of metronomic CTX plus P and C is 224 days (35-874 days). Main grade 3 side-effects are: neutropenia (2 pt; 7%), thrombocytopenia, diarrhoea, stomatitis and onycholysis (1 pt; 3.5%). No grade 4 toxicities have been observed. The rate of pts free of progression at 6 months is 80%. Overall 18 pts (64%) showed a PSA decrease ? 50% and 23 pts (82%) showed any PSA decrease from baseline (range: 4%-99%of decrease). Four pts are evaluable according to RECIST criteria: we observed 1 CR, 2 SD and 1 PD. At a median follow up of 12,4 months median time to PSA progression is 11.6 months (95% CI 8,3-15).

Conclusions: Metronomic CTX plus C in combination with DP is a feasible and tolerable regimen with a promising preliminary activity. The evaluation of plasma levels of thrombospondin-1 (TSP-1), VEGF, sVEGFR-2, VE-cadherin mRNA, and the expression of TSP-1 and VEGF in peripheral blood mononuclear cells, as potential surrogated markers of antiangiogenic activity of the combination, is ongoing.