Low-dose methotrexate and cyclophosphamide in recurrent ovarian cancer.

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Sub-category: Ovarian Cancer
Category: Gynecologic Cancer
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27, 2009 (suppl; abstr e16574)
Abstract No: e16574
Author(s): R. Scheusan,
S. Curescu, D. Stanculeanu, P. Curescu; City Hospital Timisoara,
TIMISOARA, Romania; Institute of Oncology Bucharest, Bucharest, Romania
Background: Ovarian
cancer continues to be the leading cause of death secondary to
gynecologic cancers among women. Despite the fact that new
chemotherapeutic drugs have been found effective, the prognosis of
these women continues to be poor. Metronomic chemotherapy, chronic
administration of chemotherapy at relatively low, minimally toxic doses
on a frequent schedule with no prolonged drug-free breaks, is a
potentially novel approach to the control of advanced cancer disease.
It is thought to work primarily through antiangiogenic mechanisms and
has, as an advantage, the property of significantly reducing toxic
side-effects. Purpose: to evaluate the efficacy and toxicity of
metronomic chemotherapy using low dose methotrexate and
cyclophosphamide in patients with refractory pretreated ovarian cancer.

Methods: From May 2007 to July 2008, 11 patients with refractory
pretreated ovarian adenocarcinoma were included. Patient's
characteristics: median age 51 years (range 41-64), ECOG 0-2,
progression after more than two lines of chemotherapy for recurrent
disease. Treatment: low-dose oral methotrexate 2.5 mg bd on days 1 and
2 each week and cyclophosphamide 50 mg/day administered continuously
until disease progression. Follow-up: every month clinical examination,
ECOG, blood test; every two months CA-125; every four months CT-scan.
All patients were evaluable for response and toxicity. There was no
complete response; 2 pts (18.18%) - partial response and the overall
clinical benefit rate was 54.54%. The median time to progression was
4.4 month. Main toxicities according to WHO criteria were: grade 1-2
gastrointestinal toxicities (nausea, vomiting) 4 pts (36.36%), grade
1-2 anemia 4 pts (36.36%), grade 1-2 neutropenia 2 pts (18.18%). No
grade 3-4 toxicities was observed.
Conclusions: Metronomic
metotrexate-cyclophosphamide is minimally toxic and effective in
heavily pretreated recurrent ovarian cancer. In conclusion, metronomic
regimen could represent a potentially significant palliative treatment
for these patients. A better understanding of mechanism of actions
would help determine the optimal dose and schedule for metronomic
chemotherapy regimens as antiangiogenic therapy.