The principal pharmacologic action of zoledronic acid is inhibition of bone resorption. Although the antiresorptive mechanism is not completely understood, several factors are thought to contribute to this action. In vitro, zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis. Zoledronic acid also blocks the osteoclastic resorption of mineralized bone and cartilage through its binding to bone. Zoledronic acid inhibits the increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors released by tumors.

INDICATION

Hypercalcemia of Malignancy
Zoledronic acid  is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cCa) of greater than or equal to 12 mg/dL [3.0 mmol/L] using the formula: cCa in mg/dL=Ca in mg/dL + 0.8 (4.0 g/dL – patient albumin [g/dL]).

Multiple Myeloma and Bone Metastases of Solid Tumors
Zoledronic acid is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy.

Important Limitation of Use
The safety and efficacy of Zoledronic acid  in the treatment of hypercalcemia associated with hyperparathyroidism or with other nontumor-related conditions have not been established.

Mesna reacts chemically with the urotoxic ifosfamide metabolites, acrolein and 4-hydroxy-ifosfamide, resulting in their detoxification. The first step in the detoxification process is the binding of mesna to 4-hydroxyifosfamide forming a non-urotoxic 4-sulfoethylthioifosfamide. Mesna also binds to the double bonds of acrolein and to other urotoxic metabolites and inhibits their effects on the bladder.

INDICATION

Mesna injection is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis.

Limitation of Use: Mesna injection is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia.

Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate.

The mechanism of action in rheumatoid arthritis is unknown; it may affect immune function.

INDICATION

Rheumatoid Arthritis including Polyarticular Juvenile Idiopathic

Arthritis
Methotrexate injection is indicated in the management of selected adults with severe, active rheumatoid arthritis (RA) (ACR criteria), or children with active polyarticular juvenile idiopathic arthritis (pJIA), who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).

 Psoriasis
Methotrexate injection is indicated in adults for the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis “flare” is not due to an undiagnosed concomitant disease affecting immune responses.

Limitation of Use
Methotrexate injection is not indicated for the treatment of neoplastic diseases.

Asparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine. The mechanism of action of Asparaginase is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of amino acid asparagine for their protein metabolism and survival.

INDICATION

(asparaginase Erwinia chrysanthemi) is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase.

Gemcitabine exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and also blocking the progression of cells through the G1/S-phase boundary. Gemcitabine is metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. The cytotoxic effect of gemcitabine is attributed to a combination of two actions of the diphosphate and the triphosphate nucleosides, which leads to inhibition of DNA synthesis. First, gemcitabine diphosphate inhibits ribonucleotide reductase, which is responsible for catalyzing the reactions that generate the deoxynucleoside triphosphates for DNA synthesis. Inhibition of this enzyme by the diphosphate nucleoside causes a reduction in the concentrations of deoxynucleotides, including dCTP. Second, gemcitabine triphosphate competes with dCTP for incorporation into DNA. The reduction in the intracellular concentration of dCTP (by the action of the diphosphate) enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation). After the gemcitabine nucleotide is incorporated into DNA, only one additional nucleotide is added to the growing DNA strands. After this addition, there is inhibition of further DNA synthesis. DNA polymerase epsilon is unable to remove the gemcitabine nucleotide and repair the growing DNA strands (masked chain termination). In CEM T lymphoblastoid cells, gemcitabine induces internucleosomal DNA fragmentation, one of the characteristics of programmed cell death.

INDICATION

Ovarian Cancer
Gemcitabine in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.

Breast Cancer
Gemcitabine in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.

Non-Small Cell Lung Cancer
Gemcitabine is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer.

Pancreatic Cancer
Gemcitabine is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemcitabine is indicated for patients previously treated with 5-FU.

Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases.

Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implants. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis

INDICATION

Dactinomycin, as part of a combination chemotherapy and/or multi-modality treatment regimen, is indicated for the treatment of Wilms’ tumor, childhood rhabdomyosarcoma, Ewing’s sarcoma and metastatic, nonseminomatous testicular cancer.

Dactinomycin is indicated as a single agent, or as part of a combination chemotherapy regimen, for the treatment of gestational trophoblastic neoplasia.

Dactinomycin, as a component of regional perfusion, is indicated for the palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies.

(daunorubicin) has antimitotic and cytotoxic activity through a number of proposed mechanisms of action. (daunorubicin) forms complexes with DNA by intercalation between base pairs. It inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. Single strand and double strand DNA breaks result.

(daunorubicin) may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA.

(daunorubicin) possesses an antitumor effect against a wide spectrum of animal tumors, either grafted or spontaneous.

INDICATION

Daunorubicin hydrochloride injection in combination with other approved anticancer drugs is indicated for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.

After intravenous administration of Dacarbazine  Injection, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. The average cumulative excretion of unchanged dacarbazine in the urine is 40% of the injected dose in 6 hours. Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.

In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole−4−carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine. AIC is not derived endogenously but from the injected dacarbazine, because the administration of radioactive dacarbazine labeled with 14C in the imidazole portion of the molecule (dacarbazine-2-14C) gives rise to AIC-2-14C.

Although the exact mechanism of action of Dacarbazine for Injection is not known, three hypotheses have been offered:

1. inhibition of DNA synthesis by acting as a purine analog
2. action as an alkylating agent
3. interaction with SH groups

INDICATION

Dacarbazine is indicated for the treatment of patients with metastasized malignant melanoma.

Further indications for dacarbazine as part of a combination chemotherapy are:

– advanced Hodgkin’s disease,
– advanced adult soft tissue sarcomas (except mesothelioma, Kaposi sarcoma).

After intravenous administration of Dacarbazine  Injection, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. The average cumulative excretion of unchanged dacarbazine in the urine is 40% of the injected dose in 6 hours. Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.

In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole−4−carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine. AIC is not derived endogenously but from the injected dacarbazine, because the administration of radioactive dacarbazine labeled with 14C in the imidazole portion of the molecule (dacarbazine-2-14C) gives rise to AIC-2-14C.

Although the exact mechanism of action of Dacarbazine for Injection is not known, three hypotheses have been offered:

1. inhibition of DNA synthesis by acting as a purine analog
2. action as an alkylating agent
3. interaction with SH groups

INDICATION

Dacarbazine is indicated for the treatment of patients with metastasized malignant melanoma.

Further indications for dacarbazine as part of a combination chemotherapy are:

– advanced Hodgkin’s disease,
– advanced adult soft tissue sarcomas (except mesothelioma, Kaposi sarcoma).

Although the exact mechanism of action of Bleomycin is unknown, available evidence indicates that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA and protein synthesis.

Bleomycin is known to cause single, and to a lesser extent, double-stranded breaks in DNA.  In in vitro and in vivo experiments, Bleomycin has been shown to cause cell cycle arrest in G2 and in mitosis.

When administered into the pleural cavity in the treatment of malignant pleural effusion, Bleomycin acts as a sclerosing agent.

INDICATION

Bleomycin Sulfate Injection should be considered a Palliative Treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved

Bleomycin is used to treat cancer. It works by slowing or stopping the growth of cancer cells.

This medication may also be used to control the build-up of fluid around the lungs (pleural effusion) caused by tumors that have spread to the lungs. For this condition, bleomycin is placed in the space around the lungs through a chest tube.
chemotherapeutic agents: Squamous Cell Carcinoma in Head and neck including mouth, tongue, tonsil, Nasopharynx, Oropharynx, Sinus, palate, Lip, Buccal Mucosa, Gingivae , Epiglottis, skin, Larynx, Penis, Cervix, and Vulva. Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion.