Metronomic oral cyclophosphamide has demonstrated clinical activity in various solid tumors but prospective studies in sarcoma is lacking. We conducted a phase 2 study to evaluate the efficacy and safety of MOC in patients (pts) with advanced sarcomas.
A single arm, Simon’s optimal 2-stage phase 2 trial in pts with metastatic/unresectable sarcoma who have failed first line systemic treatment with an anthracycline and/or ifosfamide. Elderly pts >65 yrs were eligible without requirement of prior treatment. Cyclophosphamide was dosed orally at 50mg once daily on a 21-day cycle until disease progression or intolerance. Tumor assessment per RECIST 1.1 was performed at baseline and every 6 weeks. Primary end point was clinical benefit rate (CBR) at 12 weeks, defined as complete/partial response/stable disease lasting ≥ 12 weeks.
Between Aug 2012 to Jun 2016, 24 pts were enrolled. One pt did not start study medication and was excluded from efficacy/safety analyses. The study proceeded into stage 2 after 3 of the initial 12 pts reported CB but study was closed early after it became apparent that the pre-specified stage 2 endpoints could not be achieved. Median age was 61yrs; 92% had ECOG 0-1; 96% received prior systemic chemotherapy, median 2 lines (range 0-5). The most common histologies were leiomyosarcoma, liposarcoma and undifferentiated pleomorphic sarcoma. Median number of MOC cycles administered was 3 (range 1-12). Reasons for treatment termination included disease and clinical progression in 91% and 4% respectively. Amongst pts treated (n = 23), 4 pts (17%) achieved CB lasting ≥12weeks. Median PFS was 1.3 mths. No objective response was noted. Treatment was generally well tolerated; there were 2 treatment-related grade 3 events (cellulitis and non-neutropenic fever). One pt died on study which was attributed to recurrent disease-related pericardial effusion with tamponade.
Metronomic oral cyclophosphamide at this current dosing regimen in an unselected sarcoma population showed only modest benefits. Larger studies are needed to define optimal dosing schedules and/or combinations in selected sarcoma pt populations.
Clinical trial identification
Registry Name: clinicaltrials.gov Registration Number: NCT01716689.
Legal entity responsible for the study
National Cancer Centre Singapore
National Medical Research Council
R. Quek: Grants/research support: Novartis, Pfizer, Eisai. Honoraria or consultation fees: Novartis, Bayer, BMS, Merck, Roche and Eisai. Participation in a company sponsored speaker\'s bureau: Novartis, Bayer, Merck and Eisai. S.L. Lim: Honoraria: Roche and Astra Zeneca. Consulting or advisory role: Roche and Astra Zeneca. Travel, accomodations, expenses: Roche. M. Leong: Travel: Janssen, R.C.L. Khoo: Travel, accomodations, expenses: Merck, K. Sittampalam: Travel, accommodation, expenses: Novartis
All other authors have declared no conflicts of interest.