1.Reduce the incidence of nephrotoxicity in patients with ovarian cancer and non-small cell lung cancer receiving cisplatin-based chemotherapy.

2.Reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a significant portion of the parotid glands.

1. Recommended dose for reduction of cumulative renal toxicity is 910 mg/m2 IV, administered once daily 30 minutes before cisplatin chemotherapy.

2. Recommended dose for reduction of xerostomia is 200 mg/m2 administered once daily 15-30 minutes before radiation therapy.

- Nausea and vomiting are common and may be severe.

- Hypotension occurs in up to 60% of patients. Usually asymptomatic. Mean time of onset is 14 minutes into the infusion. Blood pressure usually returns to normal within 5-15 minutes.

- Infusion-related reaction in the form of flushin, chills, dizziness, somnolence and sneezing.

- Hypocalcemia develops in < 1% of patients and usually is clinically asymptomatic. Amifostine affects the release of parathyroid hormone.

1.Metastatic breast cancer - First-line treatment of postmenopausal women with estrogen-receptor positive or estrogen-receptor unknown disease.

2.Metastatic breast cancer – Postmenopausal women with estrogen-receptor positive,advanced disease, and proression while on tamoxifen therapy.

3. Adjuvant treatment of postmenopausal women with hormone receptor positive early stage breast cancer.

-Asthenia. Most common toxicity,occurs 1%-20%.

-Mild nausea and vomiting.Constipation or diarrhea can also occur.

-Hot flushes. Occurs in 10% of patients.

-Dry, scaling skin rash.-Arthralgias occur in 10%-15% of patients involving hands, knes, hips, lower back and shoulders. Early morning stiffness is usual presentation.

-Headache

-Peripheral edema in 7% of patients.

-Flulike syndrome in the form of fever, malaise, and myalgias.

1.Induction therapy-0.15mg/kg/dayIV for a maximum 60 days.

2.Consolidation therapy- Should be initiated 3 weeks after completion of induction treatment and only in those patients who achieve a complete bone marrow remission. The recommended dosage is 0.15 mg/kg/dayIV for 5 days/ week for a total of 5 weeks.

-Fatigue

-Prilonged QT interval (> 500 msec) on EKG see in 40%-50% of patients. Does not usually increase upon repeat exposure to arsenic trioxide, and QT interval returns to baseline following termination of therapy. Torsade de pointes ventricular arrhythmia and/or complete AV block can be observe in this setting.

-Apl differentiation syndrome. Occurs in about 30% of patients and is characterized by fever, dyspnea, skin rash, fluid retention and weight gain, pleural and/or potential effusions. This syndrome is identical to the retinoic acid syndrome observed with retinoid therapy.

-Luukocytosis is ovserved in 50%-60% of patients with gradual increase in WBC tat peaks between 2 and 3 weeks after starting therapy. Usually resolves spontaneously without treatment and/or complication.

-Light headedness most commonly observerduringdrug infusion. Headache and insomnia.

-Mild nausea and vomiting, abdominal pain, and diarrhea.

-Musculoskeletal pain.-Mild hyperglycemia.

-Peripheral neuropathy.

-Cacinogen and teratogen.

1.Dose varies depending on specific regimens. L-Asparaginase is given at a dose of 6,000-10,000 IU/m2 IM every 3 days for a total of 9 doses. Treatment with L-Asparaginase is started after completion of chemotherapy drugs used in the induction therapy of acute lymphoblastic leukemia (vincristine, prednisone, and adriamycin)

2. Less commonly, L-Asparaginase is given asa single agent at a dose of 200 IU/kg IV for 38 consecutive days.

-Hpersensitivty reaction. Occurs in up to 25% of patients. Mild form manifested by skin rash and urticaria.Anaphylactic reaction may be life treating and presents as bronchospasm, respiratory distress, and hypotension. Resuscitation drigs and equipment should be readyily available at beside before drug treatment.

-Fever, chills, nausea, and vomiting. Acute reaction observed in about two-thirds of patients.

-Mild elevation in LFTs, including serum bilirubin, alkaline phosphate, and SGOT. Common and usually transient. Liver biopsy reveals fatty cganges.

-Increased risk of both bleeding and clotting. Alterations in clotting with decreased levels of clotting factor, including fibrinogen, factor IX and XI, antithrombin III, protein C and S, plasminogen, and alpha –2 –antiplasmin. Ovserved in over 50 % of patients.

-Pencreatities develops in up to 10% of patients. Usually manifested as a transient increase in serum amylase level with quick resolution upon cessation of therapy.

-Neurologic toxicity, including lethargy,confusion, agitation, hallucination, and/or coma. These side effects may require treatment discontinuation. Severe neurotoxicity resembles ammonia toxicity.

-Myelosuppression is mild and rarely observed.

-Decreased serum levels of insuline, lipoproteins and albumin.

-Renal toxicity. Usually mild and manifested by elevation in BUN and creatine, proteinuria, and elevated serum acid levels.

-Hypertriglyceridemia and hypercholestrolemia are common. Reversible upon dose reduction, cessation of therapy, or when antillipemic therapy is begun (gemfibrozil is not recommende, see Special Considerations).

-Hypothyrodism develops in 50% of patients.

-Headache and asthenia.

-Myelosuppression with leukopenia more common than anemia

-Nausea, abdominal pain, and diarrhea.

-Skin rash, dry skin, and rarely alopacia.

-Dry eyes, conjunctivitis, blepharitis, cataracts, corneal lesion, and visual fields degects.

-Hot flushes, decreased libido, impotence, gynaecomastia, nipple pain, and galactorrhea. Occurs in 50% of patients.

-Constipation observed in 10% of patients. Nausea, vomiting, and diarrhea occur rarely.

-Transient elevation in serum transaminases are rare.

1.Hodgkin’s disease and non hodgkin’s lymphoma.

2.Germ cell tumors.

3.Head and neck cancer.

4.Squamous cell carcinomas of the skins, cervix and vulva.

5.Sclerosing agent for malignant pleural effusion and ascites.

1.Hodgkin’s disease10 units/m2 IV on day 1 and15 every 28 days, as part of the ABVD regimen.

2.Testicular cancer: 30 units IV on day 2, 9, and 16 every 21 days, as part of the PEB regimen.

3.Intracavitary instillation into pleural space 60 units/m2.

-Skin reactions are the most common side effects and include erythema, hyperpigmentation of the skin, striae, and vesiculation. Skin peeling, thickening of the skin and nail beeds, hyperkertosis, and ulceration can also occur. These manifestation usually occur in the second and third week after treatment, when the cumulative does has reached 150-200 ubits. Alopecia is common.

-Pulmonary toxicity is dose-limiting. Occurs in 10% of patients. Usually presents as pneumonitis with cough, dyspnea, dry inspiratory crackles and infilterates on chest X-ray. This complication is both dose- and age-related. Increased incidence in patients > 70 years of age and with cumulative doses > 400 units. Rarely progresses to pulmonary fibrosis but can be fatal in about 1% of patients. PFTs are most sensitive approach to follow, with specific focus on DLCO and vital capacity. A decrease of 15% or more in the PFTs should mandate immediate stoppage of the drug.

-Hypersensitive reaction in the form of fever and chills observed in up to 25% of patients. True anphylactoid reactions are rare but more common in patients with lymphoma.

-Vascular events, including myocardinal infarction, stroke, and Raynaud’s phenomenon, are rarely reported.

-Myelosuppression is relatively mild.

-Hot flushes occur in 50% of patients, decreased libido (10%), importance (10%), and gynaecomastia (10%).

-Tumor flare. Ovserved in up to 20% of patients, usually within the first 2 weeksof starting therapy. Presents with increased bone pain, urinary retention, or back pain with spinal cord compression. May be prevented by pretreating with antiandrogenagent such as flutamide, bicalutamide, or nilutamide.

-Local discomfort at the site of injection

-Hypersensitivity reaction.

-Nausea and vomiting are rarely observed.

1.Chronicmyelogenous leukemia (CML) (standard dose).

2.Bone marrow/stem cell transplantation for refractory leukemia, lymphoma (high dose). Use in combination with cyclophosphamide as conditioning regimen prior to allogeneic stem cell transplantation for CML.

1.CML: Usual dosefor remission induction is 4-8 mg/day PO. Dosing on a weight basis is 1.8 mg/m2/day. Maintenancedose is usually 1-3 mg/day PO.

2.Transplant setting: 4 mg/kg/dayIV for 4 days to a totaldose of 16 mg/kg.

-Myelosuppression. Dose-limiting toxicity. All three cell lines are equally affected. In rare instances, delayed and refractory pancytopenia may occur, as well as agranulocytosis.

-Nausea/vomiting and diarrhea are common (>80% of patients) but generally mild with standard doses. Anorexia is also frequently observed.

-Mucositis is dose-related and may requireb intruption of therapy in some instances.

-Hyperpigmentation of skin, especially in the creases of the hands and nail beds. Skin rash and pruritus also observed.-Impotence, male sterility, amenorrhea, ovarian suppression, menopause, and infertility.

-Pulmonary symptoms, including cough, dyspnea, and fever, can be seen after long term therapy. Interstitial pulmonary fibrosis referred to as the “busulfan lung” is rare but severe side effect of therapy. May occur 1-10 years after discontinuation of therapy. Steroids may help symptoms, although the overall prognosis of this condition is poor.

1.Metastatic breast cancer – Capecitabine in combinationwith decetaxel is indicated for the treatement of patients with metastatic breast cancer after failure of prior anthracyclin-containing chemotherapy.

2.Metastatic breast cancer – indicated as mono therapy in patients refractory to both paclitaxel and anthracycline based chemotherapy or when anthracycline therapy is contraindicated.

3.Metastaticcolorectal cancer – First line therapy when fluropyrimidine therapy alone is preferred.

-Diarrhea. Dose-limiting, ovserved in up to 40% of patients. Similar to GI toxicity observed with continuous infusion 5-FU. Mucositis, loss of appetite,dehydration also noted.Hand foot syndrome (palmer-planter erythrodysesthesia). Seen in 15-20% of patients. Characterized by tingling, numbness, pain, erythema, dryness, rash, swelling, increased pigmentation, and/or pruitus of the hands and feet. Similar to dermatologic toxicity observed with continuous infusion 5-FU.

-Nausea and vomiting . occurs in 30%-40% of patients.

-Elevations in serum bilirubin (20%- 40%), alkaline phosphate, and hepatic transaminases(SGOT,SGPT). Usually transient and clinically asymptomatic.

-Mmyelosuppression is ovserved less frequently than withIV 5-FU. Leukemia more common than thrombocytopenia.

-Cardiac symptoms of chest pain, EKG changes, and serum enzyme elevation. Rare event but increased risk in patients with prior history of ischemic heart disease.

-Biepharitis, tear-duct stenosis, acute and chronic conjunctivitis.D