Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic...

The number of elderly people with soft tissue sarcoma (STS) is increasing. A sizeable population of elderly patients with STS is unfit for conventional doxorubicin- or ifosfamide-based chemotherapy. We assessed the feasibility of metronomic oral cyclophosphamide (CPM) in this population.

Patients aged 65 years or older with unresectable STS received CPM 100mg twice daily plus prednisolone 20mg daily, the first week of a 2-week cycle in the outpatient setting. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and progression-free survival.

Twenty-six patients (median age: 72, range 66-88) received a total of 330 cycles (median per patient: 10, range 2-41) as first (n=19) or second-line chemotherapy (n=7). The most frequent histological subtypes were poorly differentiated sarcoma (n=8), leiomyosarcoma and liposarcoma (n = 5 each) and angiosarcoma (n=3). Grade ≥3 lymphopenia was observed in 81% of pts but no opportunist infection occurred. Grade 3 anaemia and thrombocytopenia occurred in 2 pts (8%) each. No other grade 3-4 toxicity was seen. The response rate was 26.9% (95%CI: 9.9-44.0) and the disease control rate (responses and stable disease >12 weeks) was 69.2% (95%CI: 51.5-87.0). One complete (hepatic epithelioid haemangio-endothelioma) and 6 partial responses (including 5pts with radiation-induced sarcomas) were seen. Progression-free survival ranged from 0 to 20.6 months (median: 6.8 months) and was significantly longer in patients with radiation-induced sarcomas (median: 7.8 versus 5.2 months, p=0.02).

Metronomic CPM showed good safety results for this frail population, with promising activity in patients with radiation-induced sarcoma. Toxicity profile was favourable, allowing prolonged home staying and rare treatment discontinuations. A larger prospective study is warranted to confirm these encouraging results in elderly with STS.