2. Clinical outcomes
The median observation time from the initiation of MC was 15.9 months (range, 1–102 months), and the median duration of MC was 7 months (range, 0–61 months). Figure 1 shows the clinical courses of individual patients. Patients 1 and 2 started MC as maintenance therapy after achieving CR and remained in CR after cessation of MC, with 6 and 102.3 months of progression-free survival (PFS) time. Among the 5 patients who started MC after achieving PR or SD after the initial cytotoxic chemotherapy, 1 patient remained in SD by MC for 20.3 months, and 3 patients experienced local relapse or PD after 3 to 9.5 months, respectively. One patient with residual bone marrow disease of NBL who achieved SD by MC for 3 months, was then bridged to 131I-metaiodobenzylguanidine therapy, which led to CR. Eleven patients started MC at the disease status of PD. Disease progression could not be controlled in 6 of these patients (54.5%), and they died from their disease. The remaining 5 patients achieved SD (n = 4) or PR (n = 1) at a median of 1.5 months (1–3.8 months); however, they experienced disease progression and eventually died.
Of the 16 patients who started MC at PR/SD/PD, 9 patients (56.3%) were classified as responders. Figure 2 shows the overall and progression-free survival curves, except for 2 patients who received MC as a maintenance therapy. The overall survival rate was 56.3% at 12 months and 27.3% at 24 months (Fig. 2A), and the median survival time was 14 months (range: 1–61.4 months). The PFS rate was 14.3% at both 12 and 24 months (Fig. 2B), and the median PFS time was 4.2 months (range, 3–102 months). Figure 3 shows the overall survival curves of the patients in response to the therapy. Responders, including PR, SD, and PD at the start of MC, had longer survival times than non-responders (median 21 months vs. 5.2 months; HR, 0.07; 95% CI, 0.014–0.38;P < 0.01; Fig. 3A). Although all patients with PD at the start of MC finally died within the observation period, the survival time of responders was significantly prolonged compared to non-responders (median 19.4 months vs. 4.7 months; HR, 0.15; 95% CI, 0.029–0.79; P = 0.01; Fig. 3B). Univariate analysis revealed that tumor pathogenesis, metronomic regimen, and combination therapy did not affect survival time (Table 2).