Volume 37, Number 7, pp 714–720
2002 Facts and Comparisons
Cancer Chemotherapy Update
Estramustine and Vinblastine (EV)
Regimen for Advanced
Hormone-Refractory Prostate Cancer
J. Aubrey Waddell, PharmD, BCOP and Dominic A. Solimando, Jr., MA, FAPhA, FASHP, BCOP
The increasing complexity of cancer chemotherapy
makes it mandatory that pharmacists be familiar with
these highly toxic agents. This column reviews various
EV is used as palliative therapy for advanced hormone-
issues related to the preparation, dispensing, and admin-
refractory prostate cancer;1,2 however, estramustine/taxane
istration of cancer chemotherapy, both commercially
regimens, with their superior PSA reductions, are increas-
available and investigational. Questions or suggestions
ingly employed in this setting.3
should be addressed to: Dominic A. Solimando, Jr., Pres-
ident, Oncology Pharmacy Services, Inc., 4201 Wilson
Boulevard, #110-545, Arlington, VA 22203 or J. Aubrey
Waddell, Department of Pharmacy, Walter Reed Army
1. Follow institutional policies for preparation of haz-
Medical Center, Washington, DC 20307-5001. E-mail:
ardous medications when dispensing estramustine
The opinions or assertions contained herein are the private views 2. Dispense 140 mg capsules.
of the authors and are not to be construed as official or reflecting B. Vinblastine
the views of the U.S. Department of the Army or Department of 1. Follow institutional policies for preparation of haz-
ardous medications when preparing vinblastine.
2. Vinblastine is available from several sources as a ster-
ile powder and a 1 mg/mL ready-to-use solution. When
preparing the powder, reconstitute with 0.9% sodium
chloride or bacteriostatic 0.9% sodium chloride to
Regimen: EV (see Table 1).
achieve a final concentration of 1 mg/mL.
Origin of Name: acronym for the two drugs in the regi-
3. Vinblastine doses must have the following warning
men: estramustine and vinblastine
attached to the syringe: “Fatal if given intrathecally. For
IV use only.” Additionally, the syringe must be enclosed
COMMENTS in an overwrap bearing the following warning: “Do not
When hormone manipulations cease to be effective in remove covering until moment of injection. Fatal if
the treatment of advanced prostate cancer, there is a pallia- given intrathecally. For IV use only.”
tive role for combination chemotherapy.1,2,3 This was not 4. The dose is usually dispensed in a syringe for IV bolus
always standard practice, mainly due to low objective administration.
response rates with single chemotherapy agents in trials
conducted before the routine use of serum prostate specific DRUG ADMINISTRATION
antigen (PSA) as an effective tumor marker for prostate can- A. Estramustine: This agent is usually given as two or three
cer. In the PSA era, some chemotherapy regimens have divided doses per day. The drug should be taken at least
caused declines in PSA in up to 70% to 75% of patients, and 1 hour before or 2 hours after meals and should be swal-
clear symptomatic relief has been documented. Therefore, lowed whole with a glass of water. Milk, milk products, and
combination chemotherapy regimens continue to be studied calcium-rich foods or drugs must not be taken at the same
for tumor response, survival, and quality of life outcomes. time as estramustine.
Combination chemotherapy regimens are routinely used for B. Vinblastine: Administer as an IV bolus over 3 to 10 min-
palliative care of advanced, hormone-refractory prostate utes through the side-arm of a free-flowing IV saline or
714 Volume 37, July 2002
Cancer Chemotherapy Update
Drug Dose Route of Administered Total Dose/
Administration on Day(s) Cycle
Estramustine 600 mg/m2 PO 1–42 25,200 mg/m2
in two or three
Vinblastine 4 mg/m2 IV 1, 8, 15, 22, 29, 36 24 mg/m2
Cycle repeats: Every 8 weeks until not tolerated or disease progression.
1.Estramustine 10 mg/kg in three divided doses per day has been used in the regimen above.6–8
2.Estramustine 420 mg in three divided doses per day plus vinblastine 5 mg/m2 or 6 mg/m2 IV once each week, continu-
ously with no rest period, has been used.9,10
dextrose infusion. G. Extravasation:22–24 Vinblastine is a moderate vesicant and
extravasation should be avoided. If extravasation occurs,
SUPPORTIVE CARE stop the infusion immediately and aspirate as much of the
A. Acute Emesis Prophylaxis:4–6,9,10–14 EV causes emesis in extravasated solution as possible before withdrawing the
fewer than 10% of patients; however, nausea from EV has needle. The limb should be elevated and cooled intermit-
been reported in up to 66.7% of patients. Acute emesis tently (ice packs for 15 to 20 minutes four times daily for
prophylaxis is not generally prescribed. Because most of 3 days). Although Larson reported using cold for vinca
EV’s emetogenicity and nausea is contributed by the daily alkaloid extravasations, most other reports recommend
estramustine, patients should receive an antiemetic pre- the application of heat to the area if vinblastine is
scription to treat breakthrough nausea/vomiting. Since the extravasated.
efficacy of the serotonin antagonists is reported to dimin-
ish with repeated dosing over multiple days,15 the routine MAJOR TOXICITIES
use of these agents to manage estramustine-induced Most of the toxicities listed below are presented accord-
nausea or vomiting is not recommended. The following ing to their degree of severity. Higher grades represent more
regimens are suggested: severe toxicities. Although there are several grading systems
1. Metoclopramide 20 to 40 mg PO every 4 to 6 hours as for cancer chemotherapy toxicities, all are similar. One of the
needed; diphenhydramine 25 to 50 mg PO every 4 to frequently used systems is the National Cancer Institute
6 hours as needed for restlessness or agitation. (NCI) Common Toxicity Criteria
2. Prochlorperazine 10 mg PO every 4 to 6 hours as (http://ctep.cancer.gov/reporting/ctc.html). Oncologists gen-
needed, or 15 mg (extended-release capsule) every 8 erally do not adjust doses or change therapy for grade 1 or 2
to 12 hours as needed, or 25 mg rectally every 6 hours toxicities; but make or consider dosage reductions or thera-
as needed. py changes for grade 3 or 4 toxicities.
3. Thiethylperazine 10 mg PO every 4 to 6 hours as A. Cardiovascular:4,5 atrial fibrillation (grade 1) 1.1%, con-
needed. gestive heart failure (grade 3or 4) 3.2%, deep vein throm-
D. Hydration: No special precautions are required. bosis (grade 2, 3, or 4) 3.2%, edema (grade 1 or 2)
E. Hypersensitivity Precautions:16 No special precautions 28.9%, edema (grade 3 or 4) 2.6%, hypotension (grade 1)
are required. 1.1%, leg edema (grade 2, 3, or 4) 11.6%, myocardial
F. Hematopoietic Growth Factors:4–10,17–21 Accepted prac- infarction 2.6%, palpitations (grade 1) 1.1%, transient
tice guidelines and pharmacoeconomic analysis suggest ischemic neurologic event 2.6%.
that a chemotherapy regimen have a greater than 20% to B. Febrile Neutropenia:4,9,10 0%.
40% (depending on institutional cost differences) inci- C. Gastrointestinal:4–6,9,10 anorexia (grade 1 or 2) 10.5% to
dence of febrile neutropenia before prophylactic use of 60%, anorexia (grade 3 or 4) 0% to 6.7%, indigestion
colony-stimulating factors is warranted. Since febrile neu- (grade 1 or 2) 10.5%, nausea (grade 1 or 2) 50%, nausea
tropenia with EV is rarely reported, prophylactic use of (grade 3 or 4) 2.6%, nausea (grade 2, 3, or 4) 28.4%, nau-
colony-stimulating factors is not recommended. sea (mild) 20%, nausea/vomiting (grade 1 or 2) 66.7%,
Hospital Pharmacy 717
Cancer Chemotherapy Update
stomatitis (grade 1 or 2) 13.3%, stomatitis (grade 2) 5.3%, or platelets below 75,000 cells/mcL.5–7
vomiting (grade 1 or 2) 7.8%. 2. Amato et al held the weekly vinblastine dose for
D. Hematologic:4–6,9 anemia (grade 1 or 2) 31.6% to 73.3%, absolute granulocyte counts (AGCs) less than 900
anemia (grade 3 or 4) 0% to 23.3%, granulocytopenia cells/mcL or platelets less than 50,000 cells/mcL and
(grade 1 or 2) 10%, granulocytopenia (grade 2) 7.4%, did not restart weekly vinblastine doses until the AGC
granulocytopenia (grade 3 or 4) 8.4% to 66.7%, leukope- recovered to 1500 cells/mcL and platelets recovered to
nia (grade 1 or 2) 31.6%, leukopenia (grade 2) 8%, 100,000 cells/mcL.9
leukopenia (grade 3 or 4) 7.9%, leukopenia (grade 4) 4%, 3. In clinical practice, a pretreatment absolute neutrophil
thrombocytopenia (grade 1 or 2) 0% to 16.7%, thrombo- count (ANC) of 1000 cells/mcL and platelets of 75,000
cytopenia (grade 2, 3, or 4) 1.1%, thrombocytopenia cells/mcL are usually considered acceptable for full-
(grade 3 or 4) 3.3%. dose combination chemotherapy.
E. Infection:5,9 (grade 1 or 2) 43.3%, (grade 2 or 3) 7.4%. D. Other: Hudes et al reduced the estramustine dose by two
F. Neurologic:4,6,9,10 constipation (grade 1 or 2) 7.9% to capsules (280 mg) per day for nausea or vomiting unre-
23.3%, constipation (grade 2, 3, or 4) 3.2%, constipation sponsive to oral antiemetics, held estramustine and vin-
(grade 3 or 4) 0% to 2.6%, ileus 2.6% to 3.3%, leg cramps blastine for any grade 3 or 4 nonhematologic toxicity, and
(grade 1 or 2) 13.2%, paresthesias (grade 1 or 2) 13.2% resumed both drugs at 50% of the starting dose after
to 33.3%, peripheral neuropathy (grade 1 or 2) 10.5% to recovery from toxicity.5
G. Other:4–6,9 breast tenderness (grade 1 or 2) 26.3%, fatigue REFERENCES
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