This protocol has been superseded as it is not considered best practice for this patient population. Hodgkin lymphoma ICE (fractionated IFOSFamide cARBOplatin etoposide) (ID 63) is the preferred regimen.
A search of the literature did not find strong evidence to support the use of fractionated or infusional ICE for the treatment of Hodgkin lymphoma. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by the Phase II studies by Moskowitz et. alr and Hertzberg et. al.r
The combination of ifosfamide, carboplatin and etoposide (ICE) as salvage chemotherapy for relapsed/refractory Hodgkin lymphoma was originally studied prospectively in a phase 2 study in the 1990s. 65 consecutive patients (43 relapsed, 22 refractory) were treated with ICE salvage followed by, in responders, high-dose therapy and autologous stem cell transplant +/- radiation. The ICE protocol administered included ifosfamide given as an infusion over 24 hours and required patients to be admitted to hospital. Two cycles of ICE were given with 2 weeks between cycles.r
ICE may also be given in the outpatient setting, with the dose of ifosfamide split over 3 days (fractionated) and the cycles administered every 21 days. In a study of the fractionated regimen, 13 of the patients had Hodgkin lymphoma (11 relapsed, 2 refractory). A total of 2 cycles of ICE were planned followed by high-dose therapy and autologous stem cell transplant.r
Both the infusional and fractionated ICE regimens appear to be to be effective for salvage and stem cell mobilisation in Hodgkin lymphoma.
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trials |
Moskowitz et al. 2001 |
Yes |
N/A |
N/A |
|
Hertzberg et al. 2006 |
Yes |
Yes |
- |
Case series |
N/A |
N/A |
N/A |
- |
Observational studies |
N/A |
N/A |
N/A |
- |
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
03/03/14 |
Yes |
N/A |
- |
BCCA |
N/A |
N/A |
N/A |
- |
CCO |
N/A |
N/A |
N/A |
- |
Efficacy
Infusional
The response rate in the study of infusional ICE was 88% (CR 17, PR 38 out of 65 patients). The median interval between the 2 cycles was 16 days (range, 13-28) with 23/65 patients receiving therapy on schedule. 56 of the 57 responders proceeded to autologous transplantation and the event-free survival (EFS) and overall survival (OS) for responders were 68% and 83%, respectively, at 43 months (see graph below).r
© Blood 2001
Fractionated
In the study of fractionated ICE, all 13 patients with Hodgkin lymphoma responded (31% CR, 69% PR) and proceeded to transplant. The EFS was 69% and OS 85% at 30 months follow up. Mobilisation of PBSC following fractionated ICE was successful with the majority of patients requiring only one leukapheresis procedure.r
Toxicity
There were no toxic deaths in either the infusional or fractionated ICE studies. The toxicities in the infusional studyr are not fully described but the same group also published a study of ICE salvage in 163 patients with non-Hodgkin lymphoma.r In this group, thrombocytopenia was the dose limiting toxicity with grade 3/4 thrombocytopenia occurring in 29% of cycles given and 30% of patients requiring platelet transfusion. 13% of cycles were complicated by grade 4 neutropenia requiring hospital admission. The neutrophil nadir occurred 7 to 9 days after the beginning of the cycle. Anaemia was a common occurrence with 98 patients requiring red cell transfusions. Non-haematological toxicities were uncommon and included gross haematuria in 4 of 381 cycles, one case of reversible nephrotoxicity, two cardiac toxicities (congestive cardiac failure & supraventricular tachycardia) and 5 cases of neurological toxicity (1 peripheral neuropathy and 4 confusion due to ifosfamide-induced encephalopathy). The patients with cardiac toxicity and encephalopathy were not retreated with ICE.r
The major toxicities reported in the fractionated ICE study (which included 75 patients with non-Hodgkin and Hodgkin lymphoma) were haematological with grade 4 thrombocytopenia in 51% and grade 4 neutropenia in 55%. The neutrophil nadir occurred between days 9 and 11 post-therapy and was brief however 18 patients developed neutropenic sepsis requiring hospital admission. Non-haematological toxicities included 2 cases of CNS toxicity (grade 1 & 2), one case of haematuria and one case of (reversible) nephrotoxicity. Two patients developed cardiac complications with one case of atrial fibrillation and another of worsening cardiac failure.r