This protocol has been superseded because it is not commonly used in clinical practice.
A search of the literature did not find strong evidence to support the use of GIVE for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). 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 McQuaker et al. study.r
The GIVE regimen has been used as both a salvage and mobilization regimen in patients with relapsed or refractory lymphomas.
The combination of ifosfamide (3 g/m2 on days 1 to 3), epirubicin (100 mg/m2 on day 1) and etoposide (200 mg/m2 on days 1 to 3), repeated every 21 days for usually 3 cycles was first described by Zinzani 1994 as a salvage regimen in 20 patients with relapsed high grade non-Hodgkin lymphomas (14) or Hodgkin lymphoma (6). After three cycles, 75% of patients obtained complete or partial remission with response durations from 4 to 13 months.r
McQuaker et al 1997 compared the combination of IVE (ifosfamide 3 g/m2 D 1 to 3, Etoposide 200 mg/m2 day 1 to 3; epirubicin 50 mg/m2 day 1) with G-CSF 300 micrograms/day SCI (GIVE regimen) as a mobilisation regimen with cyclophosphamide 3 or 4 g/m2 plus G-CSF in relapsed or refractory NHL or HL. 16 patients had stem cell mobilization after GIVE and 50 patients with cyclophosphamide/G-CSF. The CD34 yield was higher with GIVE (median 8.62 X 106/L) than cyclophosphamide (3.59 X106/kg, P=0.045)2. The use of GIVE chemotherapy, in association with high dose intravenous methotrexate and autologous stem cell transplantation has also been described in six patients with enteropathy associated T cell lymphoma (EATL).r
In 2002, Zinzani et al. described the cumulative results for 62 patients treated between the years 1995 and 2000. Patients had a mixture of relapsed or refractory high and low grade NHL and HL with attempted stem cell harvest in 45 patients (successful in 74% of patients). The overall survival was 58% at 60 months and the overall response rate was 78%, where 34% of patients achieved complete remission and 44% partial remission. Two cycles were given in patients proceeding to ASCT (stem cells collected after the second cycle using filgrastim 5 micrograms/kg daily from day 6 until collection).r
The published experience with GIVE chemotherapy was expanded by Bishton et al 2007 who described a heterogeneous group of 143 (NHL and HL) patients treated with this regimen (same dosing as McQuaker et al. 1997). Complete or partial response was seen in 80.4% of patients with a five year overall survival of 53%.r
In summary, GIVE chemotherapy is a reasonable option for salvage chemotherapy although there are no direct comparisons with more widely used combinations such as the ICE or DHAP regimens. Prior cumulative anthracycline exposure is a potential limiting factor in usage. GIVE appears more effective than cyclophosphamide as a mobilisation regimen.r The dosing used in the eviQ protocol is that of McQuaker et al (1997) and Bishton et al (2007) given the larger published experience.
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Retrospective studies |
Bishton et al. 2007 |
Yes |
Yes |
Mesna 1.8 g/m2 before day 1 ifosfamide and 5.4 g/m2 upon completion. filgrastim 100 mcg daily given from day 8 for non-mobilisation cycles. |
Zinzani et al. 1994 |
Yes |
No |
Ifosfamide 2.5 g/m2 days 1 to 3, plus mesna 800 mg at 0, 4, 8, 10 hours following ifosfamide; epirubicin 100 mg/m2 day 1; etoposide 150 mg/m2 on days 1 to 3. |
Zinzani et al. 2002 |
Yes |
No |
Same as above except for the mesna dose which was 3 g/m2 on days 1 to 3 |
McQuaker et al. 1997 |
Yes |
Yes |
GCSF 300 micrograms given on day 5 |
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 |
20/12/13 |
Yes |
N/A |
Supports IVE for peripheral T-cell lymphomas
|
BCCA |
N/A |
N/A |
N/A |
- |
CCO |
N/A |
N/A |
N/A |
- |
Toxicity
The main toxicity of GIVE chemotherapy is myelosuppression with grade 3 to 4 neutropenia in 79.6% of patients with admission for intravenous antibiotics in 28.5% of cycles.r
Non-haematologic toxicity was minimal with only mild nausea and vomiting (10%) and alopecia (50%) seen in several patients. Cardiac, liver and renal toxic effects were not observed, and no fatalities due to side effects were recorded.r