Methods
Patient selection criteria and evaluation of responses
In this study, we defined MC as combination chemotherapy, including low-dose continuous oral cyclophosphamide 0.5–2.5 mg/kg/day or etoposide 10–50 mg/m2/day.4–10 We retrospectively investigated data of patients with solid tumors who experienced one or more relapse episodes or primary cases refractory to conventional chemotherapy. Of these refractory/relapsed cases, 18 patients received MC between 2012 and 2019 at our hospital.
All patients underwent regular imaging during MC, and their response to MC was assessed. Evaluation of response to MC was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as a complete response (CR) in the case of complete resolution of all demonstrable tumors; partial response (PR) in the case of 30% reduction in the longest diameter; stable disease (SD) in the case of < 30% decrease and < 20% increase in the product of diameters; and progressive disease (PD) in the case of 20% increase in the product of diameters.14
We defined responders as patients who received MC for at least 3 months and achieved CR or PR as the best response. The patients who remained with SD for at least 3 months, or the patients with progressive tumors that turned to SD that was maintained for at least 3 months after MC, were also classified as responders. Patients with tumors who received MC in PD status and continued progression during MC were defined as non-responders. If patients developed new areas of disease or showed disease-attributable clinical deterioration or death, or if the therapy was changed in spite of a less than 20% increase in tumor diameters, they were determined as progression and included as non-responders. The disease status at the start of MC was also defined following RECIST 1.1.
Overall, crude survival curves were constructed from the initiation of MC, including the period of survival after MC with other chemotherapy, radiation, or surgical treatment. To assess the tolerance of MC, we examined adverse events (AEs) and the incidence of febrile neutropenia (FN) according to Common Terminology Criteria for Adverse Events (CTCAE).15 Monthly incidences of FN during MC were assessed in 9 of 18 patients with available clinical data and compared with those during conventional chemotherapy performed before the initiation of MC (median duration was 29.2 months, range 9.8–40.2 months).