Cytotoxic drugs

 

 

Side-effects of cytotoxic drugs

The following are the Side-effects common to most cytotoxic drugs.Extravasation of intravenous drugs; A number of cytotoxic drugs will cause severe local tissue necrosis if leakage into the extravascular compartment occurs.Oral mucositis; A sore mouth is a common complication of cancer chemotherapy.Tumou lysis syndrome; Tumour lysis syndrome can occur as a result of massive cell breakdown following treatment of cancer sensitive to the chemotherapy.Hyperuricaemia; Hyperuricaemia; which may be present in high-grade lymphoma and leukaemia, can be markedly worsened by chemotherapy and is associated with acute renal failure.Nausea and vomiting; Nausea and vomiting cause considerable distress to many patients who receive chemotherapy and, to a lesser extent, abdominal radiotherapy; it may lead to refusal of further treatment.Bone-marrow suppression; All cytotoxic drugs except vincristine and bleomycin cause bone-marrow depression.Alopecia; Reversible hair loss is a common complication, although it varies in degree between drugs and individual patients.Reproductive function; Most cytotoxic drugs are teratogenic and should not be administered during pregnancy, especially during the first trimester.Thromboembolism; Venous thromboembolism can be a complication of cancer itself, but chemotherapy can also increase the risk.

 

Drugs for cytotoxic-induced side-effects

 

CALCIUM FOLINATE (Calcium leucovorin):

Indications: Adjunct to Fluorouracil Treatment of Colorectal Cancer, Bone Marrow Suppression due to Folic Acid Antagonism, Folate Deficiency, Megaloblastic Anemia, Methotrexate Toxicity, Pyrimethamine Toxicity, Sulfadiazine Toxicity, Trimethoprim Toxicity, Trimetrexate Toxicity.

Contraindications: Pernicious Anemia, Vitamin B12 Deficiency.

Dose and Administration: Prevention of methotrexate-induced adverse effects, usually started 24 hours after start of methotrexate infusion, by intramuscular injection, or by intravenous injection, or by intravenous infusion, 15 mg, repeated every 6 hours. Suspected methotrexate overdosage, by intravenous injection or by intravenous infusion (at a max. rate of 160 mg/minute), initial dose equal to or exceeding dose of methotrexate.

MESNA:

Indications: Prevention of Chemotherapy-Induced Hemorrhagic Cystitis common manifestation of urothelial toxicity, which occurs with the oxazaphosphorines, cyclophosphamide and ifosfamide.

Contraindications: hypersensitivity to thiol-containing compounds.

Dose and Administration: By intravenous injection, dose is given with oxazaphosphorine (cyclophosphamide or ifosfamide) treatment and repeated 4 and 8 hours after treatment.

 

Alkylating drugs

Extensive experience is available with these drugs, which are among the most widely used in cancer chemotherapy. They act by damaging DNA, thus interfering with cell replication. In addition to the side-effects common to many cytotoxic drugs, there are two problems associated with prolonged usage. Firstly, gametogenesis is often severely affected. Secondly, prolonged use of these drugs, particularly when combined with extensive irradiation, is associated with a marked increase in the incidence of acute non-lymphocytic leukaemia.

 

CHLORAMBUCIL:

Indications: Chronic Lymphoid Leukemia, Follicular B-Cell Lymphoma, Hodgkin’s Lymphoma, Cutaneous T-Cell Lymphoma, Minimal Change Glomerulonephritis, Mycosis Fungoides, Waldenstrom’s Macroglobulinemia. Contraindications: Lactating Mother, Pregnancy, Anemia, Bone Marrow Depression, Drug-Induced Hepatitis, Epilepsy, Interstitial Pneumonitis, Pulmonary Fibrosis, Severe Infection, Thrombocytopenic Disorder.

Dose and Administration: Hodgkin’s disease used alone, 200 micrograms/kg daily for 4–8 weeks. Non-Hodgkin’s lymphoma, used alone, initially 100– 200 micrograms/kg daily for 4–8 weeks then dose reduced or given intermittently. Chronic lymphocytic leukaemia, initially 150 micrograms/kg daily until leucocyte count sufficiently reduced; maintenance (started 4 weeks after end  of            first         course)   100 micrograms/kg      daily.       Waldenstrom’s
macroglobulinaemia, 6–12 mg daily until leucopenia occurs, then reduce to 2– 8 mg daily.

 

CYCLOPHOSPHAMIDE:

Indications: Acute Lymphoid Leukemia, Acute Monocytic Leukemia, Acute Myeloid Leukemia, Breast Carcinoma, Burkitt’s Lymphoma, Chronic Lymphoid Leukemia, Cutaneous T-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Follicular B-Cell Lymphoma, Hodgkin’s Lymphoma, Minimal Change Glomerulonephritis, Multiple Myeloma, Mycosis Fungoides, Neuroblastoma, Non-Hodgkin’s Lymphoma, Ovarian Carcinoma, Progressive Chronic Lymphocytic Leukemia, Retinoblastoma.

Contraindications: Dehydration, Lactating Mother, Pregnancy, And Severe Neutropenic Disorder. Bacterial Infection, Bone Marrow Depression, Cancer Chemotherapy Induced Hemorrhagic Cystitis, Chickenpox, Doxorubicin Induced Cardiomyopathy, Fungal Infections, Hematuria, Hemorrhagic Cystitis, Herpes Zoster, Intestinal Parasitic Infections, Protozoal Infection, Urate Renal Calculi, Viral Infection.

Dose and Administration: Oral Cyclophosphamide dosing is usually in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing. Many other regimens of intravenous and oral Cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage. Transient decreases in the total white blood cell count to 2000 cells/mm3 (following short courses) or more persistent reduction to 3000 cells/mm3 (with continuing therapy) are tolerated without serious risk of infection if there is no marked granulocytopenia.

 

Anthracyclines and other cytotoxic antibiotics

Many cytotoxic antibiotics act as radiomimetics and simultaneous use of radiotherapy should be avoided as it may result in markedly enhanced toxicity.

 

BLEOMYCIN:

Indications: Diffuse Large B-Cell Lymphoma, Follicular B-Cell Lymphoma, Hodgkin’s Lymphoma, Laryngeal Carcinoma, Malignant Tumor of Cervix, Malignant Tumor of Head and Neck, Malignant Tumour of Testis, Non-Hodgkin’s Lymphoma, Penile Carcinoma, Pleural Malignant Effusions, Squamous Cell Carcinoma, Testicular Germ Cell Tumor Carcinoma, Vulvar Carcinoma.

Contraindications: Lactating Mother, Pregnancy, Pulmonary Fibrosis, Chronic Pulmonary Disease, Interstitial Pneumonitis, And Renal Disease.

Dose and Administration: Squamous cell carcinoma, non-Hodgkin’s lymphoma, testicular carcinoma— 0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. Hodgkin’s Disease—0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. After a 50% response, a maintenance dose of 1 unit daily or 5 units weekly intravenously or intramuscularly should be given.

 

DOXORUBICIN HYDROCHLORIDE:

Indications: Produce regression of disseminated neoplastic conditions, such as acute lymphoblastic leukemia, acute myeloblastic leukemia, breast carcinoma, gastric carcinoma, Hodgkin disease, malignant lymphoma and bronchogenic carcinoma, neuroblastoma, ovarian carcinoma, soft tissue and bone sarcomas, thyroid carcinoma, transitional cell bladder carcinoma, Wilms tumor; component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.

 

Contraindications: Baseline neutrophil count less than 1,500 cells/mm 3 ; marked myelosuppression induced by previous treatment with other antitumor agents or by radiotherapy; history of hypersensitivity reactions to conventional or liposomal doxorubicin or their components; previous treatment with complete cumulative doses of daunorubicin, doxorubicin, idarubicin, or other anthracyclines and anthracenediones; severe hepatic function impairment; recent MI; severe myocardial insufficiency; severe arrhythmias.

Dose and Administration: IV 60 to 75mg/m ² as a single dose every 21 days. Give the lower dose to patients with inadequate marrow reserves because of old age, prior therapy, or neoplastic marrow infiltration.

 

EPIRUBICIN HYDROCHLORIDE:

Indications: Breast cancer with axillary node involvement.

Contraindications: Baseline neutrophil count less than 1,500 cells/mm 3; severe myocardial insufficiency or recent MI; severe arrhythmias; previous treatment with anthracyclines up to the max cumulative dose; hypersensitivity to epirubicin, other anthracyclines, or anthracenediones; severe hepatic dysfunction.

Dose and Administration: Epirubicin is given in repeated 3- to 4-wk cycles. The total dose may be given on day 1 of each cycle or divided equally and given on days 1 and 8 of each cycle. IV Recommended starting dose is 100 to 120 mg/m ² . Make dosage adjustments after the first treatment cycle based on hematologic and nonhematologic toxicities.

 

MITOMYCIN:

Indications: Metastatic Gastric Cancer, Pancreatic Carcinoma, Colorectal Cancer, Corneal Conjunctival Intraepithelial Neoplasm, Malignant Tumor of Cervix, Malignant Tumor of Head and Neck, Malignant Tumor of Urinary Bladder, Non-Small Cell Lung Cancer, Prevention of Recurrent Bladder Carcinoma.

Contraindications: Blood Coagulation Disorder, Increased Risk of Bleeding, Lactating Mother, Pregnancy, And Thrombocytopenic Disorder.

Dose and Administration: 20 mg/m2 intravenously as a single dose via a functioning intravenous catheter. Because of cumulative myelosuppression, patients should be fully reevaluated after each course of Mitomycin, and the dose reduced if the patient has experienced any toxicities. Doses greater than 20 mg/m2 have not been shown to be more effective and are more toxic than lower doses.

 

MITOXANTRONE (Mitozantrone):

Indications: Acute Myeloid Leukemia, Acute Promyelocytic Leukemia, Advanced Hormone Refractory Prostate Cancer Pain, Erythroid Leukemia, Relapsing and Remitting Multiple Sclerosis, Follicular B-Cell Lymphoma, Metastatic Breast Carcinoma, Progressive Diffuse Large B-Cell Lymphoma.

Contraindications: Lactating Mother, Pregnancy, Severe Hepatic Disease, Anemia, Bacterial Infection, Bone Marrow Depression, Chronic Heart Failure, Disease of Liver, Fungal Infections, Left Ventricular Failure, Leukopenia, Neutropenic Disorder, Radiation Therapy, Severe Cardiovascular Disease, Severe Infection, Thrombocytopenic Disorder, Viral Infection.

Dose and Administration: For induction, the recommended dosage is 12 mg/m2 of Mitoxantrone Injection daily on Days 1 to 3 given as an intravenous infusion, and 100 mg/m2 of cytarabine for 7 days given as a continuous 24-hour infusion on Days 1 to 7.

Antimetabolites

Antimetabolites are incorporated into new nuclear material or combine irreversibly with vital cellular enzymes, preventing normal cellular division.

 

CAPECITABINE:

Indications: Lymph Node Positive Colorectal Carcinoma, Metastatic Breast Carcinoma, Metastatic Colorectal Cancer, Gastric Cancer, Ovarian Carcinoma, Pancreatic Carcinoma.

Contraindications: Dihydropyrimidine Dehydrogenase Deficiency, Lactating Mother, Pregnancy, Severe Renal Disease, Anemia, Coronary Artery Disease, Hyperbilirubinemia, Infection, Necrotizing Enterocolitis, Neutropenic Disorder, Severe Diarrhea, Stomatitis, Thrombocytopenic Disorder.

Dose and Administration: PO 2,500 mg/m ² /day in 2 divided doses, approximately 12 h apart, for 2 wk. After a 1-wk rest period, this 3-wk cycle is repeated. Round to the nearest dose that gives a whole tablet size rather than cutting tablets in half. Dosing adjustments are needed for toxicities. Once the capecitabine dose is reduced, it should not be increased. See manufacturer’s recommendations.

 

CYTARABINE:

Indications: Acute lymphocytic leukemia, acute and chronic myelocytic leukemia, meningeal leukemia, erythroleukemia, non-Hodgkin lymphoma.

Contraindications: Lactating Mother, Pregnancy, Acute Pancreatitis, Anemia, Bacterial Infection, Blood Coagulation Disorder, Bone Marrow Depression, Disease of Liver, Fungal Infections, Hyperuricemia, Leukopenia, Peripheral Neuropathy, Portal Vein Obstruction, Protozoal Infection, Pulmonary Edema, Thrombocytopenic Disorder, Viral Infection.

Dose and Administration: Continuous IV infusion or rapid injection 100 to 200 mg/m ² /day or 3 mg/kg/day as a continuous IV infusion over 24 h or in divided doses by rapid injection for 5 to 10days with the courses repeated about every 2wk.

 

FLUDARABINE PHOSPHATE:

Indications: Progressive Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, Follicular B-Cell Lymphoma, and Waldenstrom’s Macroglobulinemia.

Contraindications: Lactating Mother, Pregnancy, Progressive Multifocal Leukoencephalopathy, Acutely Decompensated Chronic Heart Failure, Anemia, Autoimmune Hemolytic Anemia, Autoimmune Thrombocytopenia, Bacterial Infection, Bone Marrow Depression, Chemotherapy-Induced Hyperuricemia, Coma, Conduction Disorder of the Heart, Edema, Evans Syndrome, Feeling Agitated, Fungal Infections, Hemolytic Anemia, Herpes Zoster, Hypersensitivity Pneumonitis, Idiopathic Thrombocytopenic Purpura, Impaired Cognition, Interstitial Pneumonitis, Neutropenic Disorder, Optic Neuritis, Optic Neuropathy, Pancytopenia, Renal Disease with Mild to Moderate Renal Function Impairment, Seizure Disorder, Severe Infection, Severe Renal Disease, Thrombocytopenic Disorder, Urate Renal Calculi, Visual Changes.

Dose and Administration: By mouth, adult 40 mg/m² for 5 days every 28 days usually for 6 cycles.

 

FLUOROURACIL:

Indications: Colorectal Cancer, Gastric Cancer, Metastatic Breast Carcinoma, Metastatic Colorectal Cancer, Pancreatic Carcinoma.

Contraindications: Dihydropyrimidine Dehydrogenase Deficiency, Lactating Mother, Pregnancy, Angina, Bone Marrow Depression, Disease of Liver, Granulocytopenic Disorder, Leukopenia, Nutritional Disorder, Renal Disease.

Dose and Administration: IV Individualize dosage based on actual body weight. Use lean body weight if patient is obese or has abnormal fluid retention. 12 mg/kg/day for 4 days. Do not exceed 800 mg/day. If no toxicity is observed, give 6 mg/kg on days 6, 8, 10, and 12. Give no therapy on days 5, 7, 9, or 11. Discontinue at end of day 12, even with no apparent toxicity.

 

GEMCITABINE:

Indications: First-line treatment of locally advanced or metastatic pancreatic adenocarcinoma in patients previously treated with 5-fluorouracil; first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC); treatment of advanced ovarian cancer that has relapsed at least 6 mo after completion of platinum-based therapy; first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines are clinically contraindicated. Treatment of biliary cancer, bladder cancer, relapsed or refractory testicular cancer, squamous cell carcinoma of the head and neck.

Contraindications: Lactating Mother, Pregnancy, Bone Marrow Depression, Disease of Liver, Infection, Renal Disease.

Dose and Administration: IV 1,000 mg/m ² once weekly for 7 wk followed by 1 wk of rest.

 

METHOTREXATE:

Indications: Acute Lymphoid Leukemia, Breast Carcinoma, Burkitt’s Lymphoma, Gestational Trophoblastic Neoplasm, Juvenile Rheumatoid Arthritis, Lung Cancer, Malignant Tumor of Head and Neck, Mycosis Fungoides, Non-Hodgkin’s Lymphoma, Psoriasis, Rheumatoid Arthritis.

Contraindications: Alcoholism, Bone Marrow Hypoplasia, Interstitial Pneumonitis, Lactating Mother, Leukopenia, Methotrexate Toxicity, Pregnancy, Pulmonary Fibrosis, Severe Anemia, Severe Hepatic Disease, Severe Renal Disease, Severe Thrombocytopenia, Ascites, Bone Marrow Depression, Disease of Liver, Disorder of Immune Function, Gastric Ulcer, Peptic Ulcer, Pleural Effusions, Renal Disease, Stomatitis, Thrombocytopenic Disorder, Ulcerative Colitis.

Dose and Administration: Choriocarcinoma and similar trophoblastic diseases: Methotrexate is administered orally or intramuscularly in doses of 15 to 30 mg daily for a five-day course. Such courses are usually repeated for 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside. The effectiveness of therapy is ordinarily evaluated by 24 hour quantitative analysis of urinary chorionic gonadotropin (hCG), which should return to normal or less than 50 IU/24 hr usually after the third or fourth course and usually be followed by a complete resolution of measurable lesions in 4 to 6 weeks. One to two courses of Methotrexate after normalization of hCG is usually recommended. Before each course of the drug careful clinical assessment is essential. Cyclic combination therapy of Methotrexate with other antitumor drugs has been reported as being useful.

 

PEMETREXED:

Indications: In combination with cisplatin for the treatment of malignant pleural mesothelioma in patients whose disease is unresectable or who are otherwise not candidates for curative surgery; as a single agent for the initial treatment of locally advanced or metastatic non–small cell lung cancer after prior chemotherapy; in combination with cisplatin for the treatment of locally advanced or metastatic nonsquamous non–small cell lung cancer.

Contraindications: Lactating Mother, Pregnancy, and Renal Disease with Moderate to Severe Function Impairment, Severe Neutropenic Disorder, And Severe Thrombocytopenia.

Dose and Administration: IV Recommended dose is 500 mg/m ² infused over 10 min on day 1 of each 21-day cycle.

Vinca alkaloids and Etoposide

The vinca alkaloids, are used to treat a variety of cancers including leukaemias, lymphomas, and some solid tumours (e.g. breast and lung cancer).

 

VINCRISTINE SULPHATE:

Indications: Acute Lymphoid Leukemia, Burkitt’s Lymphoma, Diffuse Large B-Cell Lymphoma, Ewing’s Sarcoma, Follicular B-Cell Lymphoma, Hodgkin’s Lymphoma, Neuroblastoma, Non-Hodgkin’s Lymphoma, Ovarian Germ Cell Tumor Carcinoma, Rhabdomyosarcoma, Testicular Germ Cell Tumor Carcinoma, Wilms’ Tumor.

Contraindications: Charcot-Marie-Tooth Disease, Lactating Mother, Pregnancy, Bacterial Infection, Fungal Infections, Neuromuscular Disease, Protozoal Infection, Urate Renal Calculi, And Viral Infection.

Dose and Administration: The usual dose of Vincristine Sulfate Injection, USP for pediatric patients is 1.5–2 mg/m2. For pediatric patients weighing 10 kg or less, the starting dose should be 0.05 mg/kg, administered once a week. The usual dose of Vincristine Sulfate Injection, USP for adults is 1.4 mg/m2.

 

VINBLASTINE SULPHATE:

Indications: Breast Carcinoma, Gestational Trophoblastic Neoplasm, Hodgkin’s Lymphoma, Kaposi’s Sarcoma, Letterer-Siwe Disease, Malignant Tumour of Testis, Metastatic Breast Carcinoma, Mycosis Fungoides, Non-Hodgkin’s Lymphoma.

Contraindications: Bacterial Infection, Fungal Infections, Lactating Mother, Pregnancy, And Severe Leukopenia.

Dose and Administration: initiate therapy for adults by administering a single intravenous dose of 3.7 mg/m2 of body surface area (bsa). Thereafter, white‑blood-cell counts should be made to determine the patient’s sensitivity to Vinblastine sulfate.

 

ETOPOSIDE:

Indications: Refractory Testicular Neoplasm, Small Cell Lung Carcinoma, Acute Myeloid Leukemia, Burkitt’s Lymphoma, Conditioning prior to Allogeneic Hematopoietic Stem Cell Transplantation, Diffuse Large B-Cell Lymphoma, Ewing’s Sarcoma, Hodgkin’s Lymphoma, Kaposi’s Sarcoma, Multiple Myeloma, Neuroblastoma, Non-Small Cell Lung Cancer, Ovarian Germ Cell Tumor Carcinoma, Progressive Diffuse Large B-Cell Lymphoma, Testicular Germ Cell Tumor Carcinoma.

Contraindications: Lactating Mother, Pregnancy, Anemia, Bacterial Infection, Blood Coagulation Disorder, Bone Marrow Depression, Chronic Heart Failure, Drug-Induced Hepatitis, Fungal Infections, Granulocytopenic Disorder, Hypoalbuminemia, Interstitial Pneumonitis, Leukopenia, Myocardial Infarction, Protozoal Infection, Pulmonary Fibrosis, Thrombocytopenic Disorder, Viral Infection.

Dose and Administration: The usual dose of Etoposide Injection in testicular cancer in combination with other approved chemotherapeutic agents ranges from 50 to 100 mg/m2/day on days 1 through 5 to 100 mg/m2/day on days 1, 3, and 5.

 

Other antineoplastic drugs

 

BEVACIZUMAB:

Indications: Glioblastoma Multiforme of Brain, Metastatic Breast Carcinoma, Metastatic Colorectal Cancer, Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Anaplastic Astrocytoma, Ovarian Carcinoma.

Contraindications: Acute Arterial Thromboembolism, Gastrointestinal Fistula, Gastrointestinal Perforation, Hypertensive Emergencies, Intra-Abdominal Abscess, Lactating Mother, Nephrotic Syndrome, Reversible Posterior Leukoencephalopathy Syndrome, Severe Uncontrolled Hypertension, Surgical Procedure, Surgical Wound Dehiscence, Tracheoesophageal Fistula.

Dose and Administration: IV 5 or 10 mg/kg every 14 days in combination with IV 5-fluorouracil–based chemotherapy. The recommended dosage is 5 mg/kg every 14 days when administered with irinotecan/5- fluorouracil/leucovorin, and 10 mg/kg every 14 days when administered with 5- fluorouracil/leucovorin/oxaliplatin.

 

BORTEZOMIB:

Indications: Treatment of multiple myeloma; treatment of mantle cell lymphoma in patients who have received at least 1 prior therapy.

Contraindications: Lactating Mother, Pregnancy, Dehydration, Disease of Liver, Ileus, Interstitial Pneumonitis, Neutropenic Disorder, Pneumonia, Pulmonary Hypertension, Reversible Posterior Leukoencephalopathy Syndrome, Thrombocytopenic Disorder.

Dose and Administration: IV 1.3 mg/m ² as a 3- to 5-sec bolus in combination with oral melphalan and oral prednisone for nine 6-wk treatment cycles. In cycles 1 to 4, bortezomib is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29, and 32). In cycles 5 to 9, bortezomib is administered weekly (days 1, 8, 22, and 29). At least 72 h should elapse between consecutive doses.

 

CETUXIMAB:

Indications: In combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck; as single-agent treatment of recurrent or metastatic squamous cell carcinoma of the head and neck in patients in whom prior platinum-based therapy failed; in combination with irinotecan for the treatment of epidermal growth factor receptor (EGFR)– expressing metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy; as single-agent treatment of EGFR–expressing metastatic colorectal cancer after failure of both irinotecan- and oxaliplatin-based regimens and in patients who are intolerant to irinotecan-based regimens.

Contraindications: Lactating Mother, Interstitial Pneumonitis, And Pulmonary Fibrosis.

Dose and Administration: IV 400 mg/m ² as an initial loading dose administered as a 120-min infusion (max rate of infusion, 10 mg/min). The weekly maintenance dose is 250 mg/m ² infused over 60 min (max rate of infusion, 10 mg/min) until disease progression or unacceptable toxicity.

 

DACARBAZINE:

Indications: Dacarbazine for injection is indicated in the treatment of metastatic malignant melanoma. In addition, Dacarbazine for injection is also indicated for Hodgkin’s disease as a secondary-line therapy when used in combination with other effective agents.

Contraindications: Lactating Mother, Pregnancy, Severe Anemia, Severe Thrombocytopenia.

Dose and Administration: The recommended dosage is 2 to 4.5 mg/kg/day for 10 days. Treatment may be repeated at 4 week intervals. An alternate recommended dosage is 250 mg/square meter body surface/day IV for 5 days. Treatment may be repeated every 3 weeks.

 

HYDROXYCARBAMIDE (Hydroxyurea):

Indications: Chronic Myelocytic Leukemia, Malignant Melanoma, Malignant Tumor of Head and Neck, Ovarian Carcinoma, Essential Thrombocytosis, Polycythemia Vera, Sickle Cell Anemia with Crisis.

Contraindications: Cutaneous Vasculitis, Lactating Mother, Pregnancy, Severe Anemia, Severe Bone Marrow Depression, And Severe Thrombocytopenia.

Dose and Administration: Intermittent Therapy -80 mg/kg administered orally as a single dose every third day. Continuous Therapy -20 to 30 mg/kg administered orally as a single dose daily. Concomitant Therapy with Irradiation Carcinoma of the head and neck -80 mg/kg administered orally as a single dose every third day.

 

CARBOPLATIN:

Indications: Ovarian Carcinoma, Acute Myeloid Leukemia, Endometrial Carcinoma, Locally Advanced Breast Carcinoma, Malignant Tumor of Cervix, Malignant Tumor of Head and Neck, Malignant Tumor of Urinary Bladder, Malignant Tumour of Testis, Metastatic Breast Carcinoma, Metastatic Prostate Carcinoma, Non-Small Cell Lung Cancer, Progressive Diffuse Large B-Cell Lymphoma, Refractory Testicular Neoplasm, Seminoma of Testis, Small Cell Lung Carcinoma.

Contraindications: Lactating Mother, Pregnancy, Bacterial Infection, Fungal Infections, Viral Infection, Vision Loss, Carboplatin for Injection USP should not be employed in patients with severe bone marrow depression or significant bleeding.

Dose and Administration: Single Agent Therapy: Carboplatin for Injection USP, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 I.V. on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of Carboplatin for Injection USP should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000. Combination Therapy with Cyclophosphamide: In the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of: Carboplatin for Injection USP – 300 mg/m2 I.V. on day 1 every four weeks for six cycles.

 

CISPLATIN:

Indications: Malignant Tumor of Cervix, Malignant Tumor of Urinary Bladder, Malignant Tumour of Testis, Ovarian Carcinoma, Ovarian Germ Cell Tumor Carcinoma, Testicular Germ Cell Tumor Carcinoma, Adrenal Cortex Carcinoma, Conditioning prior to Allogeneic Hematopoietic Stem Cell Transplantation, Endometrial Carcinoma, Gastric Cancer, Lung Cancer, Malignant Tumor of Head and Neck, Metastatic Breast Carcinoma, Multiple Myeloma, Neuroblastoma, Non-Small Cell Lung Cancer, Osteosarcoma of Bone, Pancreatic Carcinoma, Progressive Diffuse Large B-Cell Lymphoma, Prostatic Carcinoma, Small Cell Lung Carcinoma.

Contraindications: Pre-existing renal impairment; myelosuppression; hearing impairment; history of allergic reactions to cisplatin or other platinum-containing compounds.

Dose and Administration: IV Cisplatin 20 mg/m ² /day IV for 5days every 3 wk for 3 courses (combination regimen). Single doses of cisplatin up to 120mg/m ² in combination with other antineoplastics have been used.

 

OXALIPLATIN:

Indications: Colorectal Cancer, Lymph Node Positive Colorectal Carcinoma, Metastatic Colorectal Cancer, Gastric Cancer, Pancreatic Carcinoma.

Contraindications: Lactating Mother, Pregnancy, Abnormal Hepatic Function Tests, Interstitial Pneumonitis, Peripheral Neuropathy, And Pulmonary Fibrosis.

Dose and Administration: Administer Oxaliplatin for injection in combination with 5-fluorouracil/leucovorin every 2 weeks. For advanced disease, treatment is recommended until disease progression or unacceptable toxicity. For adjuvant use, treatment is recommended for a total of 6 months (12 cycles): Day 1: Oxaliplatin for injection 85 mg/m2 intravenous infusion in 250 to 500 mL 5% Dextrose injection, USP and leucovorin 200 mg/m2 intravenous infusion in 5% Dextrose Injection, USP both given over 120 minutes at the same time in separate bags using a Y-line, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2 to 4 minutes, followed by 5-fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion. Day 2: Leucovorin 200 mg/m2 intravenous infusion over 120 minutes, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2 to 4 minutes, followed by 5-fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion.

 

ERLOTINIB:

Indications: As monotherapy for the treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) after failure of at least 1 prior chemotherapy regimen. In combination with gemcitabine as first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer.

Contraindications: Lactating Mother, Pregnancy, Abnormal Hepatic Function Tests, Adult Respiratory Distress Syndrome, Dehydration, Disease of Liver, Gastrointestinal Perforation, Hemolytic Anemia, Hepatorenal Syndrome, Hyperbilirubinemia, Interstitial Lung Disease, Interstitial Pneumonitis, Malignant Neoplasm of Liver, Myocardial Infarction, Myocardial Ischemia, Obstructive Bronchiolitis, Pulmonary Fibrosis, Renal Disease, Thrombocytopenic Disorder, Thrombotic Thrombocytopenic Purpura, Tobacco Smoker.

Dose and Administration: PO 150 mg at least 1 h before or 2 h after food. Continue treatment until disease progression or unacceptable toxicity occurs.

 

IMATINIB:

Indications: Blastic Phase Chronic Myeloid Leukemia, Chronic Eosinophilic Leukemia, Chronic Myelocytic Leukemia, Chronic Myelocytic Leukemia Accelerated Phase, Chronic Phase Chronic Myeloid Leukemia, Dermatofibrosarcoma Protuberans, Gastrointestinal Stromal Tumor, Hypereosinophilic Syndrome, Myelodysplastic/ Myeloproliferative Diseases associated with Platelet-derived Growth Factor Receptor, Philadelphia Chromosome Positive Acute Lymphoid Leukemia, Philadelphia Chromosome Positive Chronic Myelocytic Leukemia, Systemic Mastocytosis.

Contraindications: Lactating Mother, Pregnancy, Abnormal Hepatic Function Tests, Anemia, Ascites, Body Fluid Retention, Cardiogenic Shock, Cerebral Edema, Chronic Heart Failure, Chronic Heart Failure Following Myocardial Infarction, Edema, Hyperbilirubinemia, Left Ventricular Failure, Neutropenic Disorder.

Dose and Administration: Chronic phase chronic myeloid leukaemia, adult 400 mg once daily, increased if necessary to max. 800 mg daily (in 2 divided doses); child (chronic and advanced phase) 2–18 years 340 mg/m² (max. 800 mg) daily (in 1–2 divided doses), increased to 570 mg/m² (max. 800 mg) daily. Accelerated phase and blast crisis chronic myeloid leukaemia, adult 600 mg once daily, increased if necessary to max. 800 mg daily (in 2 divided doses). Acute lymphoblastic leukaemia, adult 600 mg once daily. Gastro-intestinal stromal tumours, adult 400 mg once daily. Dermatofibrosarcoma protuberans, adult 800 mg daily in 2 divided doses. Myelodysplastic/myeloproliferative diseases, adult 400 mg once daily. Advanced hypereosinophilic syndrome and chronic eosinophilic leukaemia, adult 100–400 mg once daily.

 

SORAFENIB:

Indications: Treatment of advanced renal cell carcinoma; treatment of unresectable hepatocellular carcinoma.

Contraindications: Gastrointestinal Perforation, Lactating Mother, Pregnancy, Acute Hemorrhage, Angina, Blood Coagulation Disorder, Coronary Artery Disease, Increased Risk of Bleeding, Myocardial Infarction, Myocardial Ischemia, Pancreatitis, Severe Neutropenic Disorder, Severe Thrombocytopenia, Surgical Procedure, Unstable Angina Pectoris.

Dose and Administration: adult over 18 years, 400 mg twice daily.

SUNITINIB:

Indications: Treatment of GI stromal tumor after disease progression on, or intolerance to, imatinib mesylate; treatment of advanced renal cell carcinoma.

Contraindications: Hepatic Failure, Lactating Mother, Pancreatitis, and Pregnancy.

Dose and Administration: 50 mg daily for 4 weeks, followed by a 2-week treatment-free period to complete 6-week cycle; adjust dose in steps of 12.5 mg according to tolerability; dose range 25–75 mg daily.

 

DOCETAXEL:

Indications: Breast Carcinoma, Locally Advanced Breast Carcinoma, Malignant Tumor of Head and Neck, Metastatic Breast Carcinoma, Metastatic Gastric Cancer, Metastatic Prostate Carcinoma, Non-Small Cell Lung Cancer.

Contraindications: Lactating Mother, Pregnancy, Severe Infection, Severe Neutropenic Disorder, Abnormal Hepatic Function Tests, Bone Marrow Depression, Disease of Liver, Hyperbilirubinemia, Infection, Neutropenic Disorder, Peripheral Edema, Peripheral Motor Neuropathy, Peripheral Neuropathy, Pleural Effusions, Pulmonary Edema.

Dose and Administration: IV 60 to 100 mg/m ² IV as a 1-h infusion every 3 wk.

 

IRINOTECAN HYDROCHLORIDE:

Indications: Metastatic cancer of the colon or rectum after standard treatment with fluorouracil.

Contraindications: Lactating Mother, Pregnancy, Severe Neutropenic Disorder, Bone Marrow Depression, Diarrhea, UGT1A1-28 Polymorphism.

Dose and Administration: IV Cycle 1: Irinotecan 125mg/m ² once weekly for 4 wk followed by 2wk of rest. Subsequent cycles : Give irinotecan once weekly

for 4 wk, followed by 2 wk of rest. Based on response and adverse reactions, the dose may be adjusted in 25 to 50mg/m ² increments. The weekly dose may be increased to a max of 150mg/m ² or decreased to a min of 50 mg/m ² .

 

TRASTUZUMAB:

Indications: Adjuvant treatment of HER2-overexpressing node-positive or node-negative breast cancer: as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; with docetaxel and carboplatin; as a single agent following multimodality anthracycline-based therapy.

Contraindications: Lactating Mother, Left Ventricular Dysfunction following Myocardial Infarction, Pregnancy, Pulmonary Congestion, Pulmonary Edema, Pulmonary Insufficiency Following Trauma or Surgery, Severe Dyspnea.

Dose and Administration: IV Administer according to 1 of the following doses and schedules for a total of 52 wk of therapy.