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).