Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. 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. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved. The major route of elimination is the kidneys, with 35%-71% of the infused dose excreted within 24 hours. Three phase I studies suggested the following phase II doses: 700-750 mg/m2 by short infusion, once every 2-3 weeks; 300 mg/m2/day by short infusion for 3 consecutive days, to be repeated every 2 weeks; and 300 mg/m2/day by continuous infusion for 7 consecutive days, to be repeated every 3-5 weeks. The major organ toxicity reported was renal; however, this can be adequately controlled either by hydration and osmotic diuresis or by use of continuous schedule. (Either maneuver appears to allow delivery of the recommended phase II dose with a less than 30% risk of change in serum creatinine.) In limited phase II evaluation, the drug has shown antitumor activity in patients with either refractory lymphomas or small cell lung carcinoma, with total objective response rates of 28% and 11%, respectively. In addition, it has been effective in the treatment of patients with cancer-related hypercalcemia by having an inhibitory effect on calcium reabsorption from bone. Single-agent phase II studies are planned in all major tumor types. Some are already ongoing in patients with genitourinary malignancies (renal, bladder, prostate, testicular), small cell lung carcinoma, and multiple myeloma. Metabolic studies are in progress at Memorial Sloan-Kettering Cancer Center to further elucidate the mechanism or mechanisms of the hypocalcemic effects.
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PMID:Gallium nitrate: the second metal with clinical activity. 353 51

Gallium nitrate (NSC-15200), a group IIIa metal salt, was evaluated in a phase I-II clinical trial, In phase I trial, exploring bolus administration of the drug at 3-week intervals, dose-limiting renal toxicity was observed at doses exceeding 700 mg/m2. Hematological toxicity was minimal. Ototoxicity was observed in one patient. A phase-II trial was initiated evaluating the drug at 700 mg/m2 given at 2- and 3-week intervals. Antitumor responses were observed in one patient with soft-tissuesarcoma and in two patients with small cell carcinoma of the lung. In two of these responders, pretreatment 67Ga scan was positive. Further clinical trials with the drug appear indicated, utilizing the every 2 week schedule. Pretreatment hydration combined with osmotic diuresis may ameliorate potential nephrotoxicity.
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PMID:Phase I-II clinical trial of gallium nitrate (NSC-15200). 742 36

Gallium nitrate is a group IIIa metal that was found to be active in animal species. Gallium nitrate exerts its antitumor effects via a transferrin binding mechanism. This agent is of interest in small cell lung cancer since 26 of 27 small cell carcinoma cell lines tested had increased levels of transferrin receptors. In a phase I study using a continuous infusion, the dose limiting toxicity was nausea when gallium nitrate was given at doses of 400 mg/m2/day. Other effects included elevations of serum creatinine, hypocalcemia, hypomagnesemia, decreased hearing and paresthesias. Activity has been seen in pretreated patients with malignant lymphoma, bladder carcinoma and small numbers of patients with small cell lung carcinoma. To determine the activity of continuous infusion gallium nitrate, this phase II trial was undertaken in patients with small cell lung cancer previously treated with chemotherapy.
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PMID:Phase II trial of gallium nitrate in previously treated patients with small cell lung cancer. 839 97