Chemistry Reference
In-Depth Information
understood, gallium nitrate seems to stimulate bone for-
mation and to inhibit osteoclast-mediated bone resorp-
tion (Chitamabar, 2003; Leyland-Jones, 2004).
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7.2.2.3 Antineoplastic
Gallium nitrate binds to the iron transport protein
transferrin. The inhibition of tumor growth by gal-
lium seems to relate, at least in part, to its close resem-
blance to ferric iron and its ability to interfere with the
cells' handling of iron both in acquiring it from blood
and its intracellular availability (Jakupec and Kep-
pler, 2004a,b). Studies of intravenous infusion of gal-
lium nitrate, often combined with other drugs, to treat
many different kinds of tumors have reported mixed
results. Studies of non-small cell lung cancer using
a short infusion of gallium nitrate have resulted in
little effi cacy (Chang
et al
., 1995; Webster
et al
., 2000).
Reported adverse reactions were renal impairment
and optic neuritis. Senderowicz
et al
. (1999) reported
the early termination of a trial to test the effi cacy of gal-
lium nitrate (200 mg/m
2
/day for a week administered
every 21 days) with individuals who had prostate can-
cer, because the regimen was poorly tolerated. Adverse
drug reactions included anemia, blindness, with partial
reversal, pulmonary infi ltrates, hypoxemia, and fever.
Treatment with a mixture of gallium nitrate, vinblast-
ine, and ifosfamide (VIG) for cancer of the cervix and
ovary, which had been unresponsive to other regimens,
has shown either minimal or no promising effect (Dre-
icer
et al
., 1998; Malfetano
et al
., 1995). VIG was used
in a Phase II trial of 45 patients with locally advanced
or metastatic carcinoma of the urothelium. Dreicer
et al
. (1997) reported therapeutic response in 44% but
also reported two deaths that were possibly related to
treatment, leukopenia in 62%, anemia in 69%, and car-
diac events in 13%. Gallium nitrate has been found to
benefi t patients with lymphoma, possibly because the
expression of transferrin receptors is particularly high
on lymphoma cells (Chitambar, 2004a; Warrell, Jr.
et al
.,
1983). Signifi cant response rates have been observed in
patients with diffuse large cell lymphoma, small lym-
phocytic lymphoma, and follicular lymphoma (Straus,
2003). Gallium nitrate is used in refractory bladder
cancer that has been previously treated with multiple
drugs (e.g., methotrexate, vinblastine, doxorubicin,
cisplatin). Gallium nitrate either used as a single agent
or in combination regimens has signifi cant therapeu-
tic activity (Chitambar, 2004b; Einhorn, 2003; Fagbemi
and Stadler, 1998). It has been suggested that some
of the limitations experienced with gallium nitrate as
an antineoplastic drug may result from the use of a
long exposure to steady-state levels in blood and may
be overcome by the use of oral gallium compounds
(Jakupec and Keppler, 2004a).
