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.