Thuốc
Bortezomib- Velcade
From : Dr. Nguyễn
Tài Mai
To: Dr. NĐ
(Because the question was in English, I’ll answer
in English first - and this can be translated to Vietnamese later)
Many thanks for sharing your experience and for your questions. Unfortunately
because of lack of a complete medical records and particularly also because
of medico-legal implications, I will not be able to present to you my
answer specifically about THIS case (note: for these same reasons, I've
therefore declined to render my opinion about specific cases sent to me
via the Internet).
However, in reading your case some thoughts come to mind:
(1) Is bleeding in this case related to Bortezomib?
(2) If not, then what is the mechanism of bleeding in this case ?
Chemotherapy induced bleeding occured infrequently , although thrombocytopenia
is seen commonly in oncology patients. Nadir platelet count usually appeared
from 7-15 days after chemotherapy for other chemotherapy agents and about
day 15 for bortezomib (Ref. : S. Lonial : see below) (Note: in this case,
the first dose of Velcade was given on April 23, 2008 and bleeding appeared
on April 27, which is only on day 5).
One may argue that in this specific case, patient had been treated with
other chemotherapy agents (Melphalan) , therefore his bone marrow has
been suppressed and therefore thrombocytopenia appeared earlier. This
assumption may not be correct - because if it is the case, then severe
pancytopenia already had been observed on April 23, 2008 - and this (pancytopenia)
would prevent the oncologist to initiate Velcade on the same date.
Thrombocytopenia has been associated with Bortezomib (incidence: 24-28%)
(S.Lonial et al: "Risk factors and kinetics of thrombocytopenia associated
with bortezomib for relapsed, refractory multiple myeloma" Blood,
1 Dec 2005, Vol 106, No 12, pp 3777-3784).
The mechnism of thrombocytopenia associated with bortezomib also was speculated
in this article (http://bloodjournal.hematologylibrary.org/cgi/content/full/106/12/3777)
The authors of this article also noted: "There were no reports of
serious bleeding complications from thrombocytopenia, and platelet transfusion
were required in less than 15% of all patients in this study"
This patient also known to have end-stage renal failure , and on dialysis
- therefore the next question is whether his renal failure "potentiated"
the effect of this agent (bortezomib). A recent article ađressed this
very issue: ẠẠChanan-Khan et al: "Activity and safety of bortezomib
in multiple myeloma patients with advanced renal failure: a multicenter
retrospective study" Blood, 15 March 2007, Vol 109, No 6, pp
2604-2606 (http://bloodjournal.hematologylibrarỵorg/cgi/content/full/109/6/2604).
On table 2 of this article, thrombocytopenia was observed in 7 patients
(out of a total of 39 patients in this review, or an incidence of 39%).
Among these 7 patients, servere thrombocytopenia (platelet count less
than 25 thousand/mm3) was observed in 2 patients (11%)
Therefore if bleeding in this case is truly from bortezomib, one may have
to look for another mechanism, other than thrombocytopenia- There is also
another possibility: there was NO relation between bleeding - in this
case - and bortezomib. The latter scenario seems to be more likely:
In reading this case, one is struck by the fact that his SGPT (ALT) was
markedly elevated (1000 range) (normal about 40 units/liter - but may
be different at your lab), therefore it is also consistent with a coagulation
disorder from severe liver disease. And THIS coagulation disorder (from
liver failure) is likely the culprit of his bleeding (NOT Bortezomib).
To put in another way, one may speculate that his liver disease had appeared
even BEFORE the initiation of Bortezomib.
Another possibility in this immunocompromized patient is : An overwhelming
infection started first (well known in myeloma , for example pneumonia).
Subsequent sepsis then leads to DIC and patient rapidly develops multiorgan
failure . If it is so, then in this situation, his bleeding is from DIC
(disseminated intravascular coagulation) and its associated severe thrombocytopenia
(and his bleeding is NOT from chemotherapy agents)
In summary, with the data so far, I cannot (at least not yet ) make a
connection between Bortezomib and bleeding disorder in this case.
Again many thanks for your interesting questions,
Nguyễn Tài Mai, M.D.
(YK SG 1974)
Note: above writing include general comments regarding
thrombocytopenia in oncology patients, and cannot be used for specific
clinical presentation. Opinions from attending physicians and related
specialists should be sought for individual case. - NTM
(Vị nào muốn dịch ra tiếng Việt cũng đuợc, nhưng xin đính kèm luôn cả
hàng chữ cuối cùng : "Bài nói trên chỉ có tính cách giải thíchh tổng
qúat về thiếu phiến huyết nhỏ nhận thấy trong bệnh nhân ung thư. Đối với
những truờng hợp cá biệt : xin vui lòng hỏi ý kiến cuả y sĩ điều trị và
y sĩ thỉnh vấn) - NTM
Bs Nguyễn Tài Mai, Chuyên Khoa Bệnh Máu và Ung
Thư
