NcXHF

RADIUM 223 AND METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
Table 1. Clinical Characteristics of Patients Eligible
versus Optimal for Radium 223
Eligible Patients
Two or more bone metastases
Pain from bone metastases
Adequate marrow reserve
No visceral metastases
Prior docetaxel (or ineligible/
declined docetaxel)
Optimal Patients
More than 6 bone metastases
Serum alkaline phosphatase greater than
or equal to 220 U/L
Concurrent bisphosphonate use
Question not in the setting of “superscan”
TIMING OF RADIUM 223 VERSUS CHEMOTHERAPY
OR OTHER TREATMENT OPTIONS
The treatment landscape for patients with symptomatic CRPC
is complex and manifested by the availability of a wide array of
therapeutic modalities ranging from oral androgen inhibitors,
cytotoxic chemotherapy, and external beam radiotherapy as
well as radium 223. Although radium 223 may have a place in
treatment for many patients with symptomatic CRPC, timing
its use in a treatment sequence for any specifıc patient presents a
challenging decision for a treating physician. Given the potential
for additive and long-term myelosuppression associated with
bone-target radiopharmaceuticals and cytotoxic chemotherapy,
most of the available analyses focus on the timing of radium 223
before or after docetaxel-based chemotherapy.
Tolerability of radium 223 was similar in men who had received
chemotherapy fırst and in those who declined or were
not felt to be eligible for chemotherapy. A retrospective analysis
from ALSYMPCA identifıed modestly higher rates of hematologic
toxicity in docetaxel-pretreated patients receiving
radium 223 compared with those not previously treated with
docetaxel (Table 2). There was also a higher rate of packed
red blood cell transfusion, which persisted during the 13-
week time period after completion of the sixth cycle of radium
223 therapy. 4 Nonhematologic toxicities were similar
in the two groups, although there was more nausea (40% vs.
KEY POINTS
Radium 223 delays time to symptomatic skeletal-related
events and prolongs overall survival for men with mCRPC
and more than two bone metastases with pain attributed
to bone metastases.
Greater benefit may occur in subgroups of men with more
than six bone metastases and elevated serum alkaline
phosphatase over 220 U/L.
There is a modestly higher rate of hematologic toxicity in men
receiving radium 223 after previous docetaxel therapy, but no
data exist regarding the effect of radium 223 on bone marrow
reserve for subsequent chemotherapy.
Follow-up data are limited regarding the possibility of long-term
myelosuppression and secondary myelodysplasia or leukemia.
Prostate-specific antigen changes should not be used to
determine response to treatment or duration of treatment.
Table 2. Rates and Grades of Hematologic Toxicity in
Patients Receiving Radium 223 by Prior Docetaxel
Therapy Status
Prior Docetaxel
(347 Patients)
Anemia
All grades 120 (35%) 67 (27%)
Grade 3 42 (12%) 24 (10%)
Grade 4 8 (2%) 3 (1%)
Grade 5 0 0
Neutropenia
All grades 24 (7%) 6 (2%)
Grade 3 8 (2%) 1 ( 1%)
Grade 4 3 (1%) 1 ( 1%)
Grade 5 0 0
Thrombocytopenia
All grades 53 (15%) 16 (6%)
Grade 3 15 (4%) 5 (2%)
Grade 4 16 (5%) 2 (1%)
Grade 5 0 1 ( 1%)
No Prior Docetaxel
(253 Patients)
30%) and vomiting (24% vs. 11%) for docetaxel-pretreated
compared with nonpretreated patients.
Effıcacy of radium 223 was seen in both docetaxelpretreated
and docetaxel-naive patients in ALSYMPCA.
However, subgroup analysis did identify that symptomatic
skeletal events were not substantially delayed in the
docetaxel-naive group. 5 Specifıcally, the median time to sSRE
was 17 months for patients treated with radium 223 and 19.5
months for placebo in docetaxel-naive patients (p 0.12),
whereas the median time to sSRE was 13.5 months in the radium
223 group compared with 7.8 months for placebo in
docetaxel-pretreated patients (p 0.00087). Although this is a
subgroup analysis, and this fınding warrants caution in interpretation,
it may be that patients pretreated with docetaxel with
bone pain represent an enriched, more aggressive subgroup in
which bone targeting therapy may yield a greater effect.
In terms of the tolerability of chemotherapy after radium
223, no published data exist regarding how many men
treated with radium 223 went on to receive docetaxel (or
other chemotherapy) and how they tolerated therapy in
terms of myelosuppression. This may be because of the fact
that enrollment in ALSYMPCA was restricted to men who
had either received docetaxel or were not eligible for or declined
docetaxel therapy such that there may be limited numbers
of patients from this trial who subsequently received
docetaxel. As noted above, the increased need for blood
transfusions persisted in the 13 weeks following completion
of radium 223 therapy, which suggests that tolerance of chemotherapy
may be affected, at least in the short term. Thus
the potential for higher rate of hematologic toxicity during
radium 223 treatment when docetaxel has been administered
fırst must be considered against the possibility that radium
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