1. Ovarian cancer

2. Germ cell tumors.

3. Head and neck cancer.

4. Small cell and non-smell cell lung cancer.

5. Bladder cancer

6. Relapsed and refractory acute leukemia.

7. Endometrial cancer.

1. Dose of carboplatin is usually calculated to a target area under the curve (AUC) based on the glomerular filtration rate (GFR).

2. Calvert formula is used to calculate dose: Total dose (mg)= (target AUC) x (GFR +25).*Note: Dose is in mg NOT mg/m²

3. Target AUC is usually between 5 and 7 mg / mL / min for previously untreated patients. In previously treated patients, lower AUCs (between 4 and 6 mg / mL / min) are recommended. AUCs > 7 are not associated with improved response rates.

4. Bone marrow/stem cell transplant setting: Dosage up to 1,600mg/m² divided over several days.

-Myelosuppressive is significant and dose limiting. Dose-dependent, cumulative toxicity is severe in elderly patients. Thrombocytopenia is most commonly observed, with nadir by day 21.

-Nausea and vomiting. Delayed nausea and vomiting can also occur, albeit rarely. Significantly less emetogenic than cisplatin.

-Renal toxicity. Significantly less common than with cisplatn and rarely symptomatic. Electrolyte imbalance commonly observed, with hypocalcemia, hypo kalememia, hypomagnesemia, and hyponatremia. Patients receiving other nephrotoxic drug (e.g. aminoglycosides) cocurrently with carboplatin may experience more pronounced renal toxicity.

-Peripheral neuropathy is observed in less than 10% of patients. Patients older than 65 years and/or previously treated with cisplatin may be at higher risk for developing neurologic toxicity.

-Mild and reversible elevation of liver enzymes, particularly alkaline phosphatase and SGOT.

-Allergic reaction. Can occur within a few minutes of starting therapy. Presents mainly as skin rash, urticaria, and pruritus. Bronchospasm and hypoteson are uncommon.

-Amenorrhea, azoospermia, impotence, and sterlity.Alopecia is uncommon.

1. Chronic lyphocytic leukemia (CLL).

2. Non-Hdgkin’s lymphoma.

3. Hodgkin’s lymphoma.

4. Waldenstrom’s macroglobulinemia.

-Myelosuppression is dose - limiting. Leukopenia and thrombocytopenia observed equally, with delayed and prolonged nadir occurring at 25-30 days and recovery by 40-45 days. Usually reversible, but irreversible bone marrow failure can occur.

-Mild nausea and vomiting are common.

-Pulmonary fibrosis and pneumonitis are dose related and potentially life-threatening. Relatively rare event.

-Seizures. Children with nephritic syndrome and patients receiving large cumulative doses are at increased risk. Also patients with a history of seizure disorder may be especially prone to seizures.

-Skin rash, urticaria on face, scalp, trunk with spread to legs seen in the rarly stages of therapy. Stevens - Johnson syndrome and toxic epidermal neurolysis are rare events.

-Amenorrhea, oligospermia / azoospermia, and sterility.

-Increased risk of secondary malignanices including acute myelogenous leukemia.

1. Testicular cancer

2. Ovarian cancer

3. Bladder cancer

4. Head and neck cancer

5. Esophegal cancer

6. Small cell and non-small cell lung cancer.

7. Non-Hodgkin’s lymphoma.

8. Trophoblastic neoplasms.

1. Ovarian cancer: 75mg / m² IV on day 2 every 21 days as part of the cisplatin / paclitaxel regimen, and 100 mg/m² on day 1 every 21 days as part of the cisplatin / cyclophosphamide.

2. Testicular cancer: 20mg/m² IV on day 1-5 every 21 days as part of the PEB regimen.

3. Non-small lung cancer: 60-100 mg/m²/day IV on day 1 every 21 days as part of the cisplatin / etoposide or cisplatin / gemcitabine regimens.

4. Head and neck cancer: 20mg/m²/day IV continuation infusion for 4 days.

-Nephrotoxicity. Dose-lmiting toxicity in up to 35%-40% of patients. Effects on renal function are dose-related and usually observed at 10-20 days after therapy. Generally reversible. Electrolyte abnormalities, mainly hypomagnesemia, hypocalcemia, and hypokalemia, are common. Hyperuricemia rarely occurs.

-Nausea and vomiting. Two forms are observed: acute (within the first 24 hours) and delayed (>24 hours). Early form begins within 1 hour of starting cisplatin therapy and may last for 8-12 hours. The delayed form can last for 3-5 days.

-Myelosuppressio. Occurs in 25%-30% of patients, with WBCs, platelets, and RBCs equally affected. Leukemia and thrombocytopenia are more pronounced at higher doses. Coombs-positve haemolytic anemia, independent from myelosuppression, also observed.

-Eurotoxicity. Dose-limiting toxicity,usually in th form of peripheral sensory neuropathy. Paresthesias and numbness in a classic “stocking-glove” pattern. Tends to occur after several cycles of therapy and risk increases with cumulative doses. Loss of motor function, focal encephalopathy, and seizure also observed. Neurologic effects may be reversible.

-Ototoxity with high- frequency hearing loss and tinnitus.

-Hypersensitivity reactios consisting of facial edema,wheezing, bronchospasm, and hypotension. Occur within a few minutes of drug administration

-Ocular toxicity manifested as optic neuritis, papilledema, and cerebral blindness. Altered color perception may be observed in rare cases.

-Transient elevation in LFTs, mainly SGOT and serum bilirubin.

-Metallid taste of foods and loss of appetite.

-Vascular events, including myocardial infarction, artertis, cerebrovascular accidents. Raynaud’s phenomenon has been reported.

-Azoospermia, impotence, and sterility.

Alopecia-Inappripriate secretion of antiduretic hormone (SIADH).

1. Breast cancer.

2. Non-hodkin’s lymphoma.

3. Chronic lymphocytic leukemia.

4. Ovarian cancer.

5. Bone and soft tissue sarcoma.

6. Rhabdomyosarcoma

7. Neuroblastoma and Willm’s tumor.

1. Breast cancer: When given orally, the usual dose is 100 mg/m² PO on days 1-14 given every 28 days. When administered IV, the usual dose is 600mg / m² given every 21 days as part of the AC or CMF regimens.

2. Non-Hodgkin’s lymphoma: Usual dose is 400-600mg/m2 IV on day1 every 21 days, as part of the CVP regimen, and 750 mg/m² on day1 every 21 days, as part of the CHOP regimen.

3. High-dose bone marrow transplantation: usual dose in the setting of bone marrow transplantation is 60mg/kg IV for 2 days.

Myelosuppression is dose limiting. Mainly leukepenia, wit nadir occurring at 7-14 days with recovery by 21. thrombocytopenia may occur, usually with high-dose therapy.

-Bladder toxicity in the form of hemorrhagic cystitis, dysuria, and increased urinary frequency occur in 5% - 10% of patients. Time of onset is variable and may begin within 24 hours of therapy or may be delayed for up to several weeks. Usually reversible upon discontinuation of drug. Uroproctection with mesna and hydraton must be used with high-dose therapy to prevent bladder toxicity.

-Nausea and vomiting. Usually dose-related, occurs within 2-4 hours of therapy, and may last up to 24 hours of therapy, and may last up to 24 hours. Anorexia is fairly common.

_Alopecia is relatively severe, generally starting 2-3 weeks after starting therapy. Skin and nails may become hyperpigmented.

-Amenorrhea with ovarian failure. Sterlity may be permanent.

-Cardiotoxicity is observed with high-dose therapy.

-Increased rsk of secondary malignancies, including acute myelogenous leukemia and bladder cancer, especially in patients with chronic hemorrhagic cystitis.

-Immunosuppression with an increased risk of infection

_Inappropriate secretion of antiduretic hormone (SIADH).

_Hypersensitivity reaction with rhinitis and irritation o the nose and throat. Usually self-resolving in 1-3 days, but steroids and/or diphenhydramine may be required.

1. Acute myelogenous leukemia

2. Acute lymphocytic

3. Chronic myelogenous leukemia

4. Leptomeningeal carcinometosis.

Several different doses and schedules have been used:

1. Standard dose: 100mg / m² / day IV on days 1-7 as a continuous IV nfusion, in combination with an anthracycline as induction chemotherapy for AML.

2. High-dose: 1.5-3.0 g/m² IV q 12 hours for 3 days as a high-dose, intensification regimen for AML.

3. SC: 20 mg/m² SC for 10 days per month for 6 months, associated with IFN-a for treatment of CML.

4. Intrathecal: 10-30 mg intrathecal (IT) up to 3 times weekly in the treatmant of leptomeningeal carcinomatosis secondary to leukemia or lymphoma

-Myelosuppression is dose limiting. Leukemia and thrombcytopenia are common. Nadr usually occurs by days 7-10, wth recovery by days 14-21. Myelosuppression is more severe with continuoua infusion versus bolus schedule.

-Nausea and vomiting. Mild to moderate emetogenic agent with increased severity observed with high-dose therapy. Anorexia, diarrhea, and mucositis usually occurs 1-10 days after therapy.

- Cerebellar ataxia, lethargy, and confusion. Neuro toxicity develops in up to 10% of patients. Onset usually 5 days after drug treatment and last upto 1 week. In most cases, CNS toxicities are mild and reversible. Risk factors for neuro toxicity include high-dose therapy, age older than 40, abnormal renal function with serum creatinine 1.2 mg.dL, and abnormal liver function.

-Transient hepatic dysfunction with elevation of serum transaminase and bilirubin. Most often associated with high-dose therapy.

Acute Pancreatis-Ara-C syndrome. Described in pediatric patients and represents an allergic reaction to cytarabine. Characterized by fever, myalgia, malaise, bone pain, maculopapular skin rash, conjunctivits, and oassional chest pain. Usually occurs within 12 hours of drug infusion. Steroid appearto be effective in treating and/or preventing the onset of this syndrome.

-Pulmonary complication include noncardiogenic pulmonary edema, acute respiratory distress, and Streptococus viridans pneumonia. Observed with high dose therapy.

-Erythema of skin, alopecia and hidradentis are usually mild and self-limited. Painful hand

-foot syndrome observed rarely with high-dose therapy.

- Conjunctivitis and keratitis. Associated with high dose regimens

-Seizures alterations in mental status, and fever observed within first 24 hours after IT administration.

1. Metastatic malignant melanoma

2. Hodgkin’s disease.

3. Soft tissue sarcoma

4. Neuroblastma

1. Hodgkin’s disease: 375mg/m² IV on day 1 and 15 every 28 days, as part of the AVBD regimen.

2. Melanoma: 220 mg / m² IV on days 1-3 and days 22-24 every 6 weeks, as part of the Dartmouth regimen. As a single agent, 250 mg/m² IV for 5 days 0r 800-1,000 mg / m² IV every 3 weeks.

Myelosuppression. Dose-liiting toxicity. Leukopenia and throbocytopenia are equally affected with nadir occurring at 21-25 days.

Nausea and vomiting can be severe, usually occurring within 1-3 hours and lasting for up to 12 hours. Aggressive antimetic therapy is strongly recommended.

Anorexia is common, but garrhea occurs rarely.

Flulike syndrome in the form of fever, chills, malaise, myalgias, and arthralgias. May last for several days after therapy.

Pain and burning at the site of injection.

CNS toxicity in the form o parenthesias, neurophathies, ataxia, lethargy, headache, confusion, and seizure have all been observed.

Increaded risk of photosensitivity.

Teratogenic, mutagenic, and carcinogenic.

1. Wilm’s tumor

2. Rhhabdomyosarcoma.

3. Germ cell tumors.

4. Gestational trophoblastic disease.

5. Ewing’s sarcoma

1. Adults: 0.4-0.5mg / m² IV on day1-5 every 2-3 weeks.

2. Children: 0.015 mg/kg/day (up to a maximum dose of 0.5 mg/day) IV on days 1-5 over a period of 16-45 weeks depending on the specific regimen.

-Myelosuppression. Dose-limiting and severe. Leukopenia and thrombocytopenia equally ovserved. Nadir occurs at days 8-14 after administeration.

-Nausea and vomiting. Onset within the first 2 hours of therapy, lasts for up to 24 hours, and may be severe.

-Mucositis and/or diarrhea. Usually occurs within 5-7 days and can be severe.

-Alopecia is common.

-Hyperpigmentatin of skin, erythema, and increased sensitivity to sunlight. Radiation recall reaction with erythema and desquamation of skin observed with erythema and concurrent radiation therapy.

-Potent vesicant. Tissue damage occurs with extravagant of drug.

-Elevation of serum transminases in less than 15% of patients. Dose and schedule dependent . hepato-veno-occlusive disease observed rarely with higher doses and daily schedule.

1. Acute mylogenous leukemia – Remission induction and relapse.

2. Acute lymphoblastic leukemia – Remission induction and relapse.

1. AML: 45 mg / m² IV on days 1-3 of the first course of induction therapy and on days 1 and 2 on subsequent courses. Used in combination with continuous infusion ara-C

2. All: 45 mg/m² IV on days 1-3 in combination with vincristine, prednisone, and L-Asparginase.

3. Single agent: 40 mg/m² IV every 2 weeks.

-Mylosupprssion. Dose limiting toxicity with leukepenia being more common than thrombocytopenia. Counts nadir at 10-14 days with recovery by day 21.

-Nausea and vomiting. Usually mild, occurring in 50% of patients within 1-2 hours of treatment.

-Mucisitis and diarrhea are common within the first week of treatment but not dose limiting.

-Cardiotoxicity. Acute form presents within the first 2-3 days as arrhythmias and/or conduction abnormalities, EKG changes, pericarditis, and/or mycarditis. Usually transient and mostly asymptomatic.

-Chronic form associated with dose-dependent, dilate cardiomyopathy and congestive heart failure. Incidence increases with cumulative doses greater than 550mg/m².

-Strong vesicant. Extravassation can lead to tissue necrosis and chemical thrombophlebitis at the injection site.

-Hyperpgmentation of nails, rarely skin rash, and urticaria. Radiation recall skin reaction can occur at prior sites of irradiation. Increased hypersensitivity to sunlight.

-Alopecia is universal. Usually reversible within 5-7 weeks after termination of treatment.

-Red-orange discoloration of urine. Last 1-2 days after drug administration.

HIV-assiciated,advanced Kaposi’s sarcoa – First-line therapy.

1. Available in reluctant rd 50 mg vials for IV use. Should be stored in the refrigerator but not frozen. Protect from light.

2. Visually inspect for particulate matter and discoloration.

3. Withdraw the calculated volume of drug and add an equal volume of 5% dextrose to give a final concentration of 1 mg/mL.

4. Reconstituted solution should be administered immediately or it may be stored refrigerated for 6 hours.

5. Use only 5% dextrose; do NOT use 0.9% sodium chloride.

-Myelosuppression. Dose-limiting leukopenia being moderate to severe.

-Nausea and vomiting. Occur in 50% of patients and is usually mild.

-Mucositis and diarrhea are common but not dose-limiting.

-Carditoxicity. Acute form presents within the first 2-3 days as arrythmias and/or conduction abnormalities, EKG changes, pericarditis, and/or myocarditis. Usually transient and mostly asymptomatic.

- Chronic form associated with a dose-dependent dialated cardiomyopathy associated with congestive heart failure. Incidence increases when cumulative doses are greater than 320 mg/m².

- Infusion-related reaction. Occurs within the first 5 minutes of infusion and manifested by back pain, flushing, and tightness in chest and throat. Observed in about 15% of patients and usually with the first infusion. Improves upon termination of infusion and typically does not recur upon reinstitution at a slower infusion rate.

- Vesicant. Extravagant can lead to tissue necrosis and chemical thrombophlebitis at the site of injection.

- Hyperpigmentation of nails, rarely skin rash and urticaria. Radiation recall skin reaction can occur at prior sites of irradiation. Increased hypersensitivity to sunlight.

-Alopesia. Lower incidence than its parent compound, daunonrubicin.

1. Breast cancer- Locally advanced or metastatic breast cancer after failure of prior chemotherapy. FDA-approved.

2. Non-small cell lung cancer- Locally advanced or metastatic disease after failure of prior platinum based chemotherapy. FDA-approved.

3. Small cell lung cancer.

4. Head and neck cancer.

5. Gastric cancer.

6. Refractory ovarian cancer-advanced platinum.

7. Bladder cancer.

1. Breast cancer: 60-100 mg/m² IV as a 1-hour infusion every 3 weeks or 35-40 mg / m² IV weekly for 3 weeks with 1week rest.

2. Non –small cell lung cancer: 75 mg / m² IV as a 1-hour infusion every 3 weeks or 35-40 mg / m² IV weekly for 3 weeks with 1week rest.

- Myelosuppression. Neutropenia is dose-limiting with nadir at days 7-10 and recovery by day 14. thrombocytopenia and anaemia are also observed.

- Hypersensitivity reactions occur in less than 5% of patients. Characterized by generalized skin rash, erythema, hypotension, dyspnea, and/or bronchospasm. Usually occur within the first 2-3 minutes of an infusion occur within the first 2-3 minutes of an infusion and almost always within the first 10 minutes. Most frequently observed with first or second treatment. Usually prevented by premedication with steroid; overall incidence decreased to less than 3%. When it occurs during drug infusiontreat with hydrocortisone IV, diphenhydramine 50 mg IV, and/or cimetidine 300 mg IV.

- Fluid retention syndrome. Presents as weight gain, peripheral and/or generalized edema pleural effusion, and ascites. Incidence increases with total doses >400 mg/m2. occurs in about 50% of patients. Premedication with methasone 8 mg PO bid for 3 days starting 1 day before treatment is effective in preventing and/or reducing this toxicity.

- Maculopapular skin rash and dry, itchy skin. Most commonly affect forearms and hands. Brown discoloration of fingermails may occur. Observed in up to 50% of patient usually within 1 week after therapy. Hand-foot syndrome (palmarplanter erythrodysesthesia) also described.

- Mucositis and/or diarrhea seen in 40% of patients. Mild to moderate nausea and vomiting usually of brief duration.

- Alopecia occurs in up to 80% of patients

- Peripheral neuropathy is less commonly observed with docetaxel than with paclitaxel. Mainly sensory neuropathy but motor neuropathy, autonomic neuropathy, and CNS effects also seen.

- Generalized fatigue and asthenia are commonly being seen in 60%-70% of patients. Arthralgias and myalgias also ovserved.

- Reversible elevation in serum transaminases alkaline phosphatase, and bilirubin.

- Vesicant. Phlebitis and/or swelling can be seen at the injection site.

- Fever occurs in the absence of infection in up to 30% of patients.