Description
Gallium nitrate, initially developed as an anticancer agent, was introduced by Fujisawa
as an orphan drug for the treatment of cancer-related hypercalcemia and bone
metastases that do not respond to adequate hydration. The compound acts specifically
on bone by inhibiting calcium resorption and also possibly by stimulating bone
formation. Compared with calcitonin and etidronate, gallium nitrate is more potent and
substantially longer acting. Other potential uses could be in the treatment of
osteoporosis and Paget’s disease.
Chemical Properties
white; crystal(s) powder(s) [MER06]
Chemical Properties
The structural formula of gallium nitrate is Ga(NO3)3. Gallium nitrate is an
anhydrate salt that is very soluble in water and soluble in 95%
ethanol. It is stable in commonly used intravenous fluids for
14 days at room temperature and at 5 ℃, and physically
compatible for injection with selected drug products, with the
exception of diazepam injection.This chemical is an oxidizer, and is probably combustible
Originator
Memorial Sloan-Kettering Cancer Center (U.S.A.)
Uses
Gallium is the second metal ion with clinical activity used in
cancer treatment. Gallium nitrate has demonstrated
antitumor activity in a variety of murine tumor models,
including Walker 256 carcinosarcoma, fibrosarcoma M-89,
leukemia K-1964, adenocarcinoma 755, mammary carcinoma
YMC, reticulum cell sarcoma A-RCS, lymphoma
P1798, and osteosarcoma 124F. It was, however,
ineffective in ascites, leukemias, plasma cell tumors, or
Ehrlich carcinoma. In phase II evaluation studies, gallium
nitrate has shown antitumor activity in patients with either
refractory lymphomas or small-cell lung carcinomas or
bladder cancer, with total objective response rates of 28%
and 11%, respectively. This drug has displayed its strongest
antineoplastic activity in the treatment of non-Hodgkin’s
lymphoma and bladder cancer.
In addition, according to two phase III comparative
trials,thanks to an inhibitory effect on calcium reabsorption
from bone, gallium nitrate is superior to alternative
therapies in the treatment of hypercalcemia associated with
malignancy and related disease states. Based on its clinical
efficacy, gallium nitrate (Ganite ) was approved by the Food
and Drug Administration (FDA) for the treatment of cancerassociated
hypercalcemia.
Apart from its ability to control hypercalcemia, gallium
nitrate has been shown to inhibit bone turnover and
decrease osteolysis in patients with multiple myeloma
and in patients with bone metastases from a variety of
different cancers.
Uses
Gallium(III) nitrate solution, is used as the material for producing gallium salts and for scientific research and chemical reagent. It is also used as an intermediate.
Uses
Regulator (calcium).
brand name
Ganite (Genta).
General Description
White crystals.
Air & Water Reactions
Deliquescent. Water soluble.
Reactivity Profile
Oxidizing agents, such as GALLIUM NITRATE, can react with reducing agents to generate heat and products that may be gaseous (causing pressurization of closed containers). The products may themselves be capable of further reactions (such as combustion in the air). The chemical reduction of materials in this group can be rapid or even explosive, but often requires initiation (heat, spark, catalyst, addition of a solvent). Explosive mixtures of inorganic oxidizing agents with reducing agents often persist unchanged for long periods if initiation is prevented. Such systems are typically mixtures of solids, but may involve any combination of physical states. Some inorganic oxidizing agents are salts of metals that are soluble in water; dissolution dilutes but does not nullify the oxidizing power of such materials. Organic compounds, in general, have some reducing power and can in principle react with compounds in this class. Actual reactivity varies greatly with the identity of the organic compound. Inorganic oxidizing agents can react violently with active metals, cyanides, esters, and thiocyanates.
Fire Hazard
Flash point data for GALLIUM NITRATE are not available, but GALLIUM NITRATE is probably combustible.
Pharmaceutical Applications
In clinical trials, gallium nitrate has proved to be highly active as an antitumour agent especially against non-Hodgkin’s lymphoma and bladder cancer. The cytotoxic activity of gallium nitrate has been demonstrated as single agent and as part of combination therapy, for example, together with fluorouracil. Gallium nitrate shows a relatively low toxicity and does not produce myelosuppression, which is a significant advantage over other traditional anticancer agents. Furthermore, it does not appear to show any cross-resistance with conventional chemotherapeutic agents.
These studies have also shown that gallium nitrate is able to decrease serum calcium levels in patients with tumour-induced hypercalcaemia. Subsequently, several studies have been carried out comparing traditional bisphosphonate drugs with gallium nitrate in their ability to decrease the calcium levels that are elevated as a result of cancer. Based on the clinical efficacy, gallium nitrate injections (Ganite
TM) was granted approval by the FDA for the treatment of cancer-associated hypercalcaemia. Gallium nitrate is also believed to inhibit the bone turnover and therefore to decrease osteolysis, the active reabsorption of bone material, in patients with bone metastasis secondary to other cancers.
Carcinogenicity
Studies on the antitumor activity
of gallium nitrate have shown that it is particularly active
against solid tumors. It has demonstrated antitumor
activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia
K-1964, adenocarcinoma 755, mammary carcinoma YMC,
reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma
124F.
