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Mayer et al
D. Hematopoietic Growth Factors
Accepted practice guidelines and pharmacoeconomic analysis suggest that antineoplastic regimens have a greater than
20% incidence of febrile neutropenia before prophylactic use
of colony-stimulating factors is warranted. For regimens
with an incidence of febrile neutropenia between 10% and
20%, use of colony-stimulating factors should be considered.
For regimens with an incidence of febrile neutropenia less
than 10%, routine prophylactic use of colony-stimulating
factors is not recommended.24,25
Lu et al reported febrile neutropenia in 2% of treatment
cycles.3 In studies reviewed, severe (grade 3 or 4) neutropenia was found in up to 57% of cycles.3,4 As febrile neutropenia was reported in only 2% of patients in the trials of BEEP,
prophylactic use of colony-stimulating factors is not recommended.25,26 Colony-stimulating factors should be considered if a patient experiences febrile neutropenia or grade 4
neutropenia in a prior cycle of BEEP.

Major Toxicities
Most of the toxicities listed below are presented according to
their degree of severity. Higher grades represent more severe
toxicities. Although there are several grading systems for
cancer chemotherapy toxicities, all are similar. One of the
frequently used systems is the National Cancer Institute
Common Terminology Criteria for Adverse Events (http://
evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_
QuickReference_8.5x11.pdf). Oncologists generally do not
adjust doses or change therapy for grade 1 or 2 toxicities, but
make, or consider, dosage reductions or therapy changes for
grade 3 or 4 toxicities. Incidence values are rounded to the
nearest whole percent unless incidence was less than or equal
to 0.5%.
A. Cardiovascular: Cerebellar infarction (grade 3 or 4)
1%3; hemorrhage (grade 1 or 2) 2%3; hypertension (grade
1 or 2) 14% to 37%,3,4 (grade 3 or 4) 1%.3,4
B. Hematologic: Anemia (grade 1 or 2) 40% to 50%,3,4
(grade 3 or 4) 7%3,4; febrile neutropenia (grade 3 or 4)
2%3; leukopenia (grade 1 or 2) 37%,3 (grade 3 or 4) 16%3;
lymphocytopenia (grade 1 or 2) 35%,4 (grade 3 or 4)
23%4; neutropenia (grade 1 or 2) 28% to 35%,3,4 (grade 3
or 4) 23% to 57%3; thrombocytopenia (grade 1 or 2) 30%
to 39%,3,4 (grade 3 or 4) 4% to 8%.3,4
C. Gastrointestinal: Epigastralgia (grade 1 or 2) 11%3;
nausea (grade 1 or 2) 27%3; vomiting (grade 1 or 2) 15%,3
(grade 3 or 4) 1%.3
D. Hepatic: Increased aspartate aminotransferase/alanine
aminotransferase (AST/ALT) (grade 1 or 2) 20% to
23%,3,4 (grade 3 or 4) 1% to 8%.3,4
E. Renal: Increased creatinine (grade 1 or 2) 5%3; proteinuria (grade 1 or 2) 15% to 27%,3,4 (grade 3 or 4)
0%.3,4

F. Metabolic/endocrine: Hypokalemia (grade 1 or 2)
10%,3 (grade 3 or 4) 4%3; hyponatremia (grade 1 or 2) 4%
to 12%,3,4 (grade 3 or 4) 7% to 23%.3,4
G. Infection: Infection with mild to moderate neutropenia (grade 1 or 2) 3%,3 (grade 3 or 4) 15%3; infection with
moderate to severe neutropenia (grade 3 or 4) 6%.3
H. Other: Fatigue (grade 1 or 2) 12%3; tracheoesophageal fistula (grade 3 or 4) 1%.3

Pretreatment Laboratory Studies
Needed
A. Baseline and Prior to Each Treatment
1. AST/ALT
2. Total bilirubin
3. Serum creatinine
4. Complete blood count with differential
5. Blood pressure
6. Urine analysis
B. Recommended Pretreatment Values
The reviewed studies required adequate hematologic,
renal, and hepatic functions to initiate therapy but did
not specify specific values used.3,4 In clinical practice,
a pretreatment absolute neutrophil count of 1000 cells/
µL and platelets of 75 000 cells/µL are usually considered acceptable.

Dosage Modifications
A. Renal Function
1. Bevacizumab: No adjustment required27
2. Etoposide: Creatinine clearance:
a. >50 mL/min-No adjustment required28,29
b. 15 mL/min to 50 mL/min-Give 75% dose29
c. 10 mL/min to 50 mL/min-Give 75% dose28
d. <10 mL/min-Give 50% dose28
e. <60 mL/min-Give 85% dose30
f. 45 mL/min-Give 80% dose30
g. 30 mL/min-Give 75% dose30
3.

Cisplatin:
a. Creatinine ≥1.5 mg/dL or Blood Urea Nitrogen
(BUN) ≥25 mg/dL-Do not give drug31
b. Creatinine clearance:

1.
2.
3.
4.
5.
6.

>50 mL/min-No adjustment required28
10 mL/min to 50 mL/min-Give 75% dose28
<10 mL/min-Give 50% dose28
<60 mL/min-Give 75% dose30
<45 mL/min-Give 50% dose30
<30 mL/min-Do not give drug30

B. Hepatic
1. Bevacizumab: No information available30
2. Etoposide:
a. Bilirubin 1.5 mg/dL to 3 mg/dL-Give 50%
dose32
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
Table of Contents for the Digital Edition of Hospital Pharmacy - June 2017
