Complications and toxicity
Cycle-specific toxicities are described in Table 3. A total of 87 cycles
of VDC or ICE were received; 45 were VDC cycles, and 42 were ICE cycles.
Seven (16%) VDC cycles were associated with chemotherapy delays
compared to 4 (10%) ICE cycles. The most common reason for chemotherapy
delay was delayed count recovery. Febrile neutropenia was the most
common complication observed, seen in 20 (44%) VDC cycles and 18 (43%)
ICE cycles. Unplanned hospitalizations were seen in 22 (49%) of VDC
cycles and 22 (52%) of ICE cycles, most commonly due to febrile
neutropenia. Similarly, 28 (62%) VDC cycles and 36 (86%) of ICE cycles
were associated with an unplanned visit to the ED or clinic, for reasons
such as blood product transfusions, fever evaluation, and symptom
management.
VDC cycles were also associated with 1 (2%) electrolyte disturbance and
1 (2%) hemorrhagic cystitis, both grade 1. No VDC cycles led to acute
kidney injury or resulted in the need for home hydration.
ICE cycles were further complicated by 1 (2%) grade 1 acute kidney
injury (with rapid recovery) and 2 (5%) minor electrolyte disturbance.
Five (12%) led to the use of pre-emptively arranged home hydration for
future subsequent cycles after experiencing significant delayed nausea
and vomiting post carboplatin in an initial cycle. No ICE cycles were
associated with hemorrhagic cystitis.
Overall, among 14 patients treated with VDC-ICE therapy, 13 (93%) had
an unplanned admission to the hospital (Supplemental Table S1). All
patients had unplanned ED/clinic visits (Supplemental Table S1).
Thirteen patients (93%) experienced at least one episode of Grade 3
febrile neutropenia, and 8 (57%) patients experienced grade 3
anorexia/malnutrition (Table 4). Other Grade 3 criteria observed
included: nausea/vomiting/dehydration (n=7); diarrhea (n=1); hypotension
in the setting of hematemesis (n=1); peripheral neuropathy (n=1); and
bacteremia (n=1). No non-hematologic grade 4 or 5 toxicities were
observed. Other complications patients experienced included acute kidney
injury (n=1) and hepatotoxicity (n=2) (Table 3 and 4). For the patients
with hepatotoxicity, tumor burden likely was a contributory factor.
Hepatotoxicity occurred only in patients with underlying diagnosis of
MRT of the liver. Two (14%) patients required escalation of care to the
ICU during therapy (Supplemental Table S1), both of which were found to
have progressive disease shortly after ICU admission. Another patient
was transferred from a different institution to the ICU due to
complications that began prior to their first cycle of VDC-ICE
chemotherapy, so this ICU admission was not attributed to the treatment
plan.
There was no documented ototoxicity or clinically significant
cardiotoxicity, defined as a decrease in ejection fraction of greater
than 15 percent. Seven patients (50%) experienced chemotherapy
administration delays. Six (43%) patients had delays during VDC cycles,
and 4 (29%) experienced delays during ICE cycles (Table 3). Eight
patients (57%) required chemotherapy dose modifications, with the most
commonly modified drug being vincristine (n=5), followed by doxorubicin
(n=3), carboplatin (n=3), ifosfamide (n=2), and etoposide (n=2)
(Supplemental Table S1). No treatment-related mortality was observed.