Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4441-4442
CORRESPONDENCE
Lack of Response to Short-Term Use of Clarithromycin (BIAXIN) in
Multiple Myeloma
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LETTER |
To the Editor:
In multiple myeloma (MM), interleukin-6 (IL-6) has been identified as a
major cytokine involved in proliferation of the tumor clone and in
tumor-associated toxicities.1,2 The central role of IL-6 as
a growth factor for MM suggests that strategies to block its effects
could be exploited therapeutically.
Preclinical studies have demonstrated that the macrolide antibiotic
clarithromycin has immunomodulatory properties mediated in part by
suppression of IL-6 and other cytokines.3 Preliminary clinical experience has subsequently also suggested efficacy of clarithromycin in the treatment of MM.4 Durie et
al4 reported 6 complete and 7 partial responses from a
group of 23 evaluable patients treated with clarithromycin as a single
agent. This observation, even in abstract form, has generated
widespread patient and physician interest in the use of clarithromycin
as a novel therapy in this disease.
To further explore the use of this agent in myeloma, we have treated 23 patients with clarithromycin. The regimen consisted of clarithromycin
at 500 mg administered orally twice daily on a 2 weeks on, 1 week off
schedule as previously described.4 No concurrent
chemotherapy, including the use of steroids, was allowed.
Bisphosphonate treatment was permitted during the treatment period.
Response to clarithromycin treatment was assessed using National Cancer
Institute of Canada criteria.
Table 1 shows the demographic
characteristics, prognostic variables, and prior treatment modalities
for enrolled patients. Twenty-three myeloma patients with varying
disease status were treated. Five patients were treatment naïve
at the time of initiation of therapy. Of these 5 patients, 2 had
smouldering myeloma, 2 had asymptomatic stage 1 disease, and 1 patient
with active myeloma had consistently refused all conventional therapies
over a 1-year period before beginning clarithromycin. The status of the
remaining patients at the time of treatment included relapsed disease
(n = 3), plateau phase (n = 3), stable residual disease after bone marrow transplantation (n = 1), relapsed disease posttransplant (n = 3), and refractory disease (n = 8). Five of the 23 patients had rapidly progressive myeloma at the time of initiation of treatment.
Of the 23 patients enrolled, 3 received clarithromycin for less than 1 month and were thus inevaluable at the time of analysis. One patient
discontinued treatment because of rapid progression of disease and 2 discontinued therapy because of drug toxicity before completing the
first cycle of treatment: 1 because of gastrointestinal intolerance and 1 because of a potential drug interaction with Dilantin.
The median duration of therapy for the remaining 20 evaluable patients
was 3.2 months (range, 1 to 6 months). Of the 20 patients, there were
no partial or complete remissions using standard response criteria. Ten
patients had stable disease and 10 patients progressed on therapy. No
patients with rapidly progressing myeloma at the time of initiation of
clarithromycin displayed stable disease on treatment.
In this phase II pilot study, we were unable to confirm activity of
short-term treatment with clarithromycin. However, it is possible that
a small treatment effect may have been missed because 11 of the 20 evaluable patients on this trial had relatively chemotherapy-insensitive disease (smouldering, plateau phase, or
refractory myeloma). Nevertheless, these results suggest that clarithromycin is not an effective single agent therapy for myeloma.
A.K. Stewart
S. Trudel
B.M. Al-Berouti
D.M. Sutton
J. Meharchand
The Princess Margaret Hospital
Toronto,
Ontario, Canada
C. Shustik
Royal Victoria Hospital
Montreal, Quebec, Canada
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REFERENCES |
1.
Klein B, Zhang XG, Lu ZY, Bataille R:
Interleukin-6 in human multiple myeloma.
Blood
85:863, 1995[Free Full Text]
2.
Hallek M, Bergsagel PL, Anderson K:
Multiple myeloma: Increasing evidence for a multistep transformation process.
Blood
91:3, 1998[Free Full Text]
3.
Matsuoka N, Eguchi K, Kawakami A, Tsuboi M, Kawabe Y, Aoyagi T, Nagataki S:
Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells.
Clin Exp Immunol
104:501, 1996[Medline]
[Order article via Infotrieve]
4.
Durie BGM, Villarete L, Farvard A, Ornopia M, Urnovitz HB:
Clarithromycin (Biaxin) as primary treatment for myeloma.
Blood
90:579a, 1997 (abstr, suppl 1)
