BC Cancer Protocol Summary for Etoposide, Ifosfamide-Mesna
(SAIME) Alternating with vinCRIStine, DOXOrubicin and
Cyclophosphamide (with or without Mesna)(SAVAC or SAVACM) with
Filgrastim Support at TWO Weekly Intervals for Newly Diagnosed
Ewing Sarcoma/ Ewing Family of Tumours, Desmoplastic Intra-
abdominal Small Round Blue Cell tumour or Rhabdomyosarcoma
Protocol Code SAALT2W
Tumour Group Sarcoma
Contact Physician Dr. Christine Simmons
ELIGIBILITY:
• Newly diagnosed Ewing sarcoma/Ewing family of tumours, intra-abdominal small
round blue cell tumour or rhabdomyosarcoma or high grade small round blue cell
tumours in the adolescent/young adult age group (less than 30)
• SAVACM to be used rather than SAVAC if pelvic radiation planned
• Normal kidney, cardiac and hepatic function
TESTS:
Before SAIME usually given Cycle day 1:
• Baseline and before each treatment: CBC & diff, platelets, sodium, potassium,
phosphate, albumin, bilirubin, creatinine
• If Day 1 CBC and diff or creatinine levels are ABNORMAL, recheck CBC and diff or
creatinine on Day 4. Notify MD of Day 4 results prior to administering chemotherapy
on Day 5
• Urine dipstick for blood before each treatment and every 8 hours during treatment –
if positive at any time, notify doctor and send urine sample for urinalysis for
verification and accurate determination of hematuria - refer to supportive care
protocol SCMESNA (follow SCMESNA (SAIME/SAAVIME3) pre-printed order)
• Imaging of primary site and any metastatic disease is done after three full
alternations – approximately week 11 of protocol.
Before SAVAC/SAVACM usually Cycle Day 15:
• Baseline and before each treatment: CBC and diff, platelets, creatinine, bilirubin,
ALT, alk phos, GGT, LDH
• Urine dipstick for blood:
SAVAC: before each treatment – if positive at any time, notify doctor and send urine
sample for urinalysis for verification and accurate determination of hematuria – if
hematuria verified, switch to SAVACM
BC Cancer Protocol Summary SAALT2W 1/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
SAVACM: before each treatment and every 8 hours during treatment – if positive at
any time, notify doctor and send urine sample for urinalysis for verification and
accurate determination of hematuria - refer to supportive care protocol SCMESNA
(follow SCMESNA (SAVACM) pre-printed order)
• If clinically indicated: ECG
PREMEDICATIONS:
SAIME
• Antiemetic protocol for high-moderate emetogenic chemotherapy protocols (see
SCNAUSEA)
SAVAC/SAVAC+M
• Antiemetic protocol for high emetogenic chemotherapy protocols (see SCNAUSEA)
TREATMENT:
7 full alternations of SAIME with SAVAC/SAVACM (14 chemotherapy
administrations). SAVACM to be used rather than SAVAC if pelvic radiation
planned
SAIME: Given daily for 5 consecutive days
• Repeat EVERY 4 WEEKS, alternating with SAVAC or SAVACM every 2 weeks for
total of 7 cycles (14 chemotherapy treatments). Note DOXOrubicin is generally
given to a total dose of 375 mg/m² (5 cycles) – after that cumulative dose is reached
then omit DOXOrubicin from SAVAC or SAVACM – giving only vinCRIStine and
cyclophosphamide in the usual doses.
• During radiation therapy (XRT). DOXOrubicin may be omitted from SAVAC or
SAVACM depending on the location of the radiation. Sometimes SAIME may be
repeated depending on clinical situation. DOXOrubicin is not reintroduced until at
least three weeks after XRT has been completed.
• Filgrastim (G-CSF) to start Day 8 – Filgrastim may not be used to escalate doses
beyond those specified in the protocol. The patient should be treated with filgrastim
(G-CSF) in doses sufficient to allow full dose treatment on schedule using the dose
modifications below. Note: this guideline applies only if the treatment is potentially
curative and after experience with one or more cycles of treatment indicate filgrastim
(G-CSF) is required. (See Pharmacare guidelines). Therefore alternate funding for
first cycle is required.
BC Cancer Protocol Summary SAALT2W 2/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
SAIME
Hour Drug Dose BC Cancer Administration Guideline
0 etoposide 100 mg/m² IV in 250 to 1000 mL NS over 45 min to 1 h
30 min (use non-DEHP equipment with 0.2
micron in-line filter)
1 mesna 360 mg/m² IV in 100 mL NS over 15 min
followed by
ifosfamide* 1800 mg/m2 IV in 500 mL NS over 1 h
2.25 –9 After completion of Ifosfamide infusion:
For patients receiving MESNA orally, no further hydration needed.
For patients receiving MESNA by IV, continue hydration with
NS IV at 250 mL/h until after Hour 9 Mesna.
5 and 9 360 mg/m2 IV in 100 mL NS over 15 min
Mesna** or
720 mg/m² PO in carbonated beverage as outpatient
9 NS IV at 150 mL/h for 8 hours
• For patients who are hydrating well and have not had hematuria, IV
hydration may be discontinued daily after Hour 9 Mesna bolus.
• ONLY patients with hematuria requiring Mesna dose adjustments are
required to be treated on a 24 hour schedule.
* Total cumulative dose of Ifosfamide generally should not exceed 72 g/m² as there is an
increased risk of Renal Fanconi Syndrome in children.
** If tolerated, may use oral mesna for last day of inpatient SAIME to allow for more timely
discharge
BC Cancer Protocol Summary SAALT2W 3/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
ALTERNATING SAIME WITH SAVAC+M – TWO WEEKLY
EVALUATE TUMOUR
RESPONSE -
CONFERENCE FOR
DECISION RE: LOCAL
TREATMENT
1 5 9 13 17 21 25
SAIME SAIME SAIME SAIME SAIME SAIME SAIME
DOXOrubicin
TOTAL DOSE IS
350 mg/m2 - given SAVAC+M SAVAC+M SAVAC+M SAVAC+M SAVAC+M SAVAC+M SAVAC+M
any 5 of 7 cycles
3 7 11 15 19 23 27
of SAVAC+M -
NOT during
radiation of vital
organs. SURGERY - CHEMO is DELAYED;
RESUME ALTERNATIONS once healed.
RADIATION - ALTERNATING CHEMO is
CONCURRENT - but DO NOT GIVE
DOXOrubicin in SAVAC+M if radiation will
hit VITAL ORGANS. Restart DOXOrubicin
3 weeks AFTER COMPLETION
RADIATION
BC Cancer Protocol Summary SAALT2W 4/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at your own risk and is subject to BC Cancer's terms of use
available at www.bccancer.bc.ca/terms-of-use
SAVAC/SAVAC+M
• SAVACM rather than SAVAC to be used if pelvic radiation planned
• Repeat every 4 weeks, alternating with SAIME every 2 weeks.
• SAVAC/SAVACM is not usually given during radiotherapy unless the tumour is
extremity primary. Protocol suggests dropping DOXOrubicin from SAVAC or
SAVACM. SAIME may be repeated depending on clinical situation. DOXOrubicin is
not reintroduced until at least three weeks after XRT has been completed.
• Admit for cycle one of SAVAC If well tolerated, subsequent cycles may be given as
an outpatient in ACU providing patients on SAVACM can tolerate oral MESNA
SAVAC:
Drug Dose BC Cancer Administration Guideline
vinCRIStine 1.5 mg/m² IV in 50 mL NS over 15 min
(maximum dose = 2 mg)
DOXOrubicin* 75 mg/m2 IV push
cyclophosphamide 1200 mg/m2 IV in 500 mL D5W-1/2 NS over 1 hour
*Total cumulative dose should not exceed 375 mg/m².
SAVACM:
Drug Dose BC Cancer Administration Guideline
vinCRIStine 1.5 mg/m² IV in 50 mL NS over 15 min
(maximum dose = 2 mg)
DOXOrubicin* 75 mg/m2 IV push
mesna 240 mg/m2 Hour 0:30: IV in 100 mL D5W over 15 min
cyclophosphamide 1200 mg/m2 IV in 500 mL D5W-1/2 NS
over 1 hour
mesna 240 mg/m2 Hours 5 and 8: IV in 100 mL D5W over 15
min OR 480 mg/m2 PO in carbonated
beverage
*Total cumulative dose should not exceed 375 mg/m².
BC Cancer Protocol Summary SAALT2W 5/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or
treatment. Use of these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
HYDRATION for SAVACM:
Hours 1:45 to 11 IV D5W-1/2 NS at 250 mL/h
Hours 11 to 24 IV D5W-1/2 NS at 125 mL/h
If no hematuria and patient is drinking well, IV hydration may
be discontinued at Hour 15.
DOSE MODIFICATIONS for BOTH SAIME AND SAVAC/SAVACM:
If dose reduced, stay at reduced dose level for the rest of program.
1. Hematological: for treatment day counts reduce ALL drugs
ANC (x109/L) Platelets (x109/L) Dose (ifosfamide, etoposide,
DOXOrubicin,
cyclophosphamide and
mesna)
greater than and greater than or Give 100%
or equal to equal to 100
0.75
less than 0.75 or less than 100 Delay for 1 week*
if counts recover then give
100%
If counts do NOT recover by
Day 22
- then reduce dose by 20%
and continue with Q 2 weekly
dosing if possible
*If unable to give full dose after 1 week delay – use dose reduction as indicated
or consult Dr. Simmons
2. Nausea and vomiting: more than 10 episodes despite antiemetics and/or
requiring parenteral fluid support, reduce dose of ALL DRUGS to 80%
3. Hematuria: If on SAVAC use SAVACM for subsequent cycles. If on SAIME
or SAVACM, refer to SCMESNA
4. Hepatic dysfunction: Dose modifications may be required for DOXOrubicin
and vinCRIStine (see BC Cancer Drug Manual)
BC Cancer Protocol Summary SAALT2W 6/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or
treatment. Use of these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
5. Renal Toxicity: SAIME: If serum creatinine increases greater than 100% or
greater than twice institutional normal at any time during treatment (measured
Days 1 and 4), estimate creatinine clearance using formula:
N* x (140 - Age) x Weight (kg)
Creatinine clearance =
Serum creatinine
* For males N= 1.23; For females N=1.04
• If CrCl greater than 50mL/min, continue with ifosfamide. If CrCl less than
50mL/min, discontinue course. If ifosfamide is discontinued midcycle,
continue with MESNA for 48 hours.
• If renal function does not return to normal by next cycle, GIVE
ETOPOSIDE AS A SINGLE AGENT.
• SAVAC/SAVACM: Dose modification may be required for
cyclophosphamide (see BC Cancer Drug Manual)
6. CNS toxicity: If drowsiness develops discontinue all sedating medications
and continue ifosfamide. If patient is confused, unrousable or comatose,
ifosfamide should be discontinued. If ifosfamide is the cause of CNS
depression, then it should not be given again. If the CNS changes are not due
to ifosfamide, then ifosfamide can be reinstituted providing the previous
medications contributing to CNS changes are not given with it. If a seizure
occurs while on ifosfamide, then that cycle is to be discontinued. Further
cycles may be given if the patient is on anticonvulsants.
7. Etoposide hypotensive reaction: Stop etoposide infusion. Lie patient flat
and run NS IV. Give diphenhydrAMINE 25 to 50 mg IV and hydrocortisone
100 mg IV. Resume etoposide infusion in 20 to 30 minutes, once patient is
stable. For subsequent doses of etoposide, pre-medicate with
diphenhydrAMINE 25 to 50 mg IV and hydrocortisone 100 mg IV.
PRECAUTIONS:
1. Neutropenia: Fever or other evidence of infection must be assessed
promptly and treated aggressively.
2. Hypersensitivity: Monitor infusion of etoposide for the first 15 minutes for
signs of hypotension. Refer to BC Cancer Hypersensitivity Guidelines.
3. Venous access: ensure good venous access prior to starting ifosfamide so
that MESNA can be given at completion of ifosfamide.
4. Cardiac Toxicity: DOXOrubicin is cardiotoxic and must be used with caution
in patients with severe hypertension or cardiac dysfunction. Cardiac
assessment is recommended if lifelong dose of 375 mg/m2 is exceeded (see
BC Cancer Drug Manual).
5. Extravasation: DOXOrubicin and vinCRIStine cause pain and tissue
necrosis if extravasated. Refer to BC Cancer Extravasation Guidelines.
BC Cancer Protocol Summary SAALT2W 7/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or
treatment. Use of these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
Call Dr. Christine Simmons or tumour group delegate at (604) 877-6000 or
1-800-663-3333 with any problems or questions regarding this treatment
program.
References:
1. Schuchter LM, Hensley ML, Meropol NJ, et al. 2002 Update of recommendations for the use
of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American
Society of Clinical Oncology. J Clin Oncol 2002;20(12):2895-903.
2. Reaman G, Womer R, Krailo MD, Marina N. Memo: Chemotherapy for localized Ewing
sarcoma: AEWS0031 results. In: Members C, editor. Arcadia, CA: COG; 2007. p. 1.
3. Womer RB, West DC, Krailo, MD et al. Randomized Controlled Trial of Interval-Compressed
Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children’s
Oncology Group. J Clin Oncol 2012; 30:4148-4154.
BC Cancer Protocol Summary SAALT2W 8/8
Activated: 1 Jun 2016 Revised: 1 May 2021(IV bag size, infusion time, in-line filter clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or
treatment. Use of these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
