Oral metronomic chemotherapy using cyclophosphamide in metastatic patients (pts) after standard treatment: Results of a randomiz

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Author(s): S. Clisant,
A. Adenis, E. Dansin, C. Desauw, M. Degardin, L. Mortier, C. Fournier,
N. Penel; Centre Oscar Lambret, Lille, France; Hopital Saint Vincent,
Lille, France; CHRU, Lille, France
Background: Oral
metronomic chemotherapy (OMC) has antiangiogenic properties and
megestrol acetate (MA) is an orexigen used to maintain the general
condition in critically ill pts. Anecdotal responses have been reported
with each treatment. We hypothesized that each treatment offer disease
control without significant severe toxicity.
Methods: This
multi-center-randomized study was aimed to assess the efficacy and
tolerance of both treatments. Primary endpoint was stable disease rate
at 2 months: 2mSD (RECIST). Main eligibility criteria were as follows:
non-breast cancer, pts with progressive disease refractory to standard
therapies or without established standard care, ECOG=0-1, neither
hypercalcemia nor hypoalbuminemia. Pts were randomized to receive MA
160 mg b.i.d or OMC 50 mg b.i.d until severe toxicity or progression.
The sample size calculation was based on Simon Minimax design (?=10%, ?
=90%, P0=5%, P1=20%). The second stage was allowed because at least
2mSD were seen among 12 first pts.
Results: 88 pts were
included from 9/2006 to 12/2008 (44 in each arm). Median age was 61
(22-84). Most common primaries were: colorectal cancer (30 pts), soft
tissue sarcoma (17), lung cancer (13), head & neck (8) and unknown
primaries (4). The median number of previous lines of treatment was 4
(0-10). As of 28 December 2008, 80 pts are assessable for primary
endpoint: 6/40 pts (15%) experienced 2mSD in OMC arm whereas 2/40 pts
(5%) in MA arm. Three long-lasting SD (6 months +) are currently being
observed in 3 pts receiving OMC (2 sarcomas and 1 RCC). No Grade 3 or 4
toxicity was notified. Treatment was discontinued in 1 case because of
MA- induced deep venous thrombosis.
Conclusions: OMC and MA
offer SD in patients with advanced, refractory and progressive tumors,
without any significant toxicity. The non-progression rate with OMC
(15%) is in a same range of efficacy that was recently reported with
new targeted therapy or anti-angiogenic agents administered in such
pts. The accrual is now completed, and a longer follow-up is necessary
to better analyze the clinical benefit and the prognostic factors.