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

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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
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
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
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.