(Antimetabolites agents, Alkylating agents ...Adverse effects of anticancer drugs (Antimetabolites...

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Adverse effects of anticancer drugs (Antimetabolites agents, Alkylating agents , Antimicrotubule agents, Miscellaneous agents , Immune therapies and Biologically directed therapies ) 1

Transcript of (Antimetabolites agents, Alkylating agents ...Adverse effects of anticancer drugs (Antimetabolites...

Adverse effects of anticancer drugs (Antimetabolites agents, Alkylating agents , Antimicrotubule

agents, Miscellaneous agents , Immune therapies and Biologically directed therapies )

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1- Nausea and vomiting Three different types of Chemotherapy-induced nausea and vomiting (CINV) have been identified: acute, delayed and anticipatory. Chemotherapy agents are divided into four emetogenic levels Highly emetogenic Alkylating agents (Mechlorethamine, Carmustine, Dacarbazine and Cisplatin).

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Moderate emetogenic Alkylating agents (Ifosfamide , cyclophosphamide, carboplatin and oxaliplatin ) Antimetabolites agents (Cytarabine ) Anti-microtubule (Daunorubincin , Doxorubincin, epirubicin , idarubicin and irinotecan ) Immune therapies (Interleukin 2)

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Low emetogenic

Antimetabolites agents (Fluorouracil, Gemcitabine ,methotrexate and pemetrexed)

Miscellaneous agents (Mitomycin C)

Biologically directed therapies (Bortezomib, cetuximab and trastuzumab)

Antimicrotubule agents (Docetaxel , paclitaxel,Topotecan, Etoposide and Mitoxantrone)

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Minimal emetogenic

Antimetabolites agents (Fludarabine)

Miscellaneous agents (Bleomycin)

Antimicrotubule agents (Vinblastine, vincristine and vinorelbine)

Alkylating agents (Busulfan)

Biologically directed therapies (Bevacizumab and Rituximab)

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 Various combinations of the following classes of medications are used for treatment nausea and vomiting

Serotonin receptor antagonists (5-‐HT3) ( odansetron, grainsetron and palonosetron )

Dopamine receptor antagonists (D2) (metoclopramide)

Systemic Corticosteroids (dexmethasone)

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2- Myelosuppression Manifestations include low WBC especially neutrophil , platelets and erythrocytes. Drugs causing myelosuppression Antimetabolites agents Antimicrotubule agents except estramustine and

vincristine. Alkylating agents except oxaliplatin and cisplatin Miscellaneous agents/ Mitomycin C Immune therapy Biologically directed therapies molecular targets/ Bortezomib Monoclonal antibodies/ Alemtuzumab and Gemtuzumab

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Neutropenia

When the Absolute neutrophil count (ANC) falls below 500/ mm3, infection risk increases.

The diagnosis of infection in the neutropenia patient is complicated by the lack of WBCs.

Infection in cancer patient can be prevented by Colony- stimulating factors (CSFs)

Granulocyte Colony- stimulating factors ( G-CSF) ( filgrastim) ( pegfilgrastim)

Granulocyte – macrophage Colony- stimulating factors ( GM-CSF) ( sargramostim)

The side effects of G-CSFs is bone pain , increase in lactate dehydrogenase, alkaline phosphatase and uric acid levels.

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The side effects of GM-CSF include constitutional symptoms, such as low grade fever , myalgia, arthralgia's, lethargy and mild headache. GM-CSF may also increase in liver transaminases. At higher doses of GM-CSFs pleural and pericardial effusions, capillary link syndrome and thrombus formation may occur.

Both G-CSF and GM-CSF may produce mild erythema at subcutaneous injection sites, as well as generalized maculopapular rash with either subcutaneous or intravenous administration.

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Thrombocytopenia

Chemotherapy induced thrombocytopenia puts the patient at risk for significant bleeding.

Platelet transfusion is indicated for

Patients with a platelet count of < 10000/mm3.

Patients with lesser degrees of thrombocytopenia with sign and symptoms of hemorrhage.

Patients with thrombocytopenia who must undergo surgical procedure .

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Oprelvekin ( inteleukine 11) is indicated for

Patients with nonmyeloid malignancies who experienced significant thrombocytopenia with a prior cycle of chemotherapy.

Patients with high risk for severe thrombocytopenia after chemotherapy.

• Side effects of oprelvekin include fluid retention and cardiac toxicity, especially tachycardia and atrial fibrillation and flutter.

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Anemia

The incidence of anemia depends on several factors, including the type and duration of therapy and the type and stage of the underlying malignancy.

Multiple conditions are known to cause anemia in cancer patients including chronic gastrointestinal blood loss, nutrient deficiency, chemotherapy and radiation, bone marrow invasion by the tumor, hemolysis, renal dysfunction and anemia of chronic disease.

Anemia in cancer patients treated by erythropoietic therapy (epoetin alfa and darbepoetin alfa).

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3- Alopecia

Alopecia from chemotherapy is usually temporary.

Loss of hair is not limited to the scalp; any area of the body may be affected.

Cryotherapy ( local application of ice ) and scalp tourniquet have been investigated as methods of preventing alopecia. These techniques are not uniformly effective and contraindicated in patients with cancers that may metastasize to the scalp, such as leukemia and lymphoma.

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Drugs causing alopecia

Antimetabolites (cytarabine).

Antimicrotubule agents (paclitaxel, docetaxel, irinotecan, etoposide , daunorubicin, doxorubicin, idarubicin and mitoxantrone)

Miscellaneous agents (Bleomycin)

Alkylating agents (Ifosfamide, Cyclophosphamide)

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4- Mucositis

The gastrointestinal mucosa is composed of epithelial cells with a high mitotic index and rapid turnover rate, making it a common site of chemotherapy induced toxicity.

The inflammation, or mucositis, can lead to painful ulceration, local infection, and inability to eat, drink, or swallow.

Patients at high risk for this toxicity include ( Those with poor dentition, high dose chemotherapy, or radiation therapy involving oropharynx).

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The use of ice ( oral cryotherapy) may decrease the risk for mucositis by decreasing drug delivery to the oral mucosa.

Keratinocyte growth factor (palifermin) are used for prevention of chemotherapy induced mucositis.

When mucositis has developed, treatment mainly supportive, including use topical or systemic analgesics and oral hygiene( including the rinses ( chlorhexidine).

Sever cases of mucositis may lead to dehydration and require intravenous hydration.

Local infection and reactivation of herpes simplex viruses are common in this patients. Suspicious lesions should be cultured, and appropriate antifungal and/ or antiviral therapy should be added.

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• Mucosal damage can occur at any point along the entire length of the GI tract. In the lower portion of the GI tract, this damage is usually manifested as diarrhea and abdominal pain.

• Support with IV fluids and electrolyte supplementation should be initiated in sever case. And also can be treated with antispasmodics such as loperaminde.

• The somatostatin analog octreotide has been used to treat sever cases of chemotherapy induced diarrhea.

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Drugs causing mucositis

Antimetabolites agents (Fluorouracil, capecitabine, cytarabine, Fludarabine, methotrexate and pemetrexed)

Antimicrotubule agents (paclitaxel, irinotecan, toptecan,etoposide , daunorubicin, doxorubicin, idarubicin, mitoxantrone and Vinblastine).

Miscellaneous agents (Bleomycin)

Alkylating agents (oxaliplatin ,procarbazine)

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Immune therapy (interleukin-2)

Biologically directed therapies (bortezomib ,Gefitinb , imatinib, tretinoin,cetuximab and tositumomab).

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5- Flu-like syndrome with fever and arthralgias

Antimetabolites agents (Cytarabine A and Gemcitabine )

Miscellaneous agents (Bleomycin)

Immune therapies (interferon alfa and interleukin-2)

Premedication and scheduled dosing with acetaminophen or an NSAID may alleviate flu- like symptoms.

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6- Rash

Antimicrotubule agents(Docetaxel)

Antimetabolites agents (Fluorouracil, Cytarabine, Gemcitabine, 6- Mercaptopurine , Pemetrexed)

Miscellaneous agents (Bleomycin , Arsenic trioxide, Asparaginase)

Immune therapies (interleukin-2)

Biologically directed therapies (imatinib, Alemtuzumab and Tositumomab )

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7- Hypersensitivity reaction

Antimicrotubule agents ( paclitaxel and Docetaxel)

Alkylating agents (carboplatin and oxaliplatin)

Miscellaneous agents (Bleomycin and Asparaginase)

Biologically directed therapies (cetuximab, rituximab , Tositumomab, gemtuzumab ozogamicin, ibrotumomab and trastuzumab)

Premedicate with acetaminophen, diphenhydramine with or without dexamethasone to prevent hypersensitivity reactions.

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8- Infertility

High rates of fertility deficits and sexual dysfunction have been noted for both men and women.

In men the antitumor drugs have been shown to produce severe oligospermia or azoospermia as well as infertility.

Important factors for infertility in men include age, total dose, duration of therapy, and type of drug.

In women, toxic effects on the ovaries result clinically in amenorrhea , vaginal epithelia atrophy, and menopausal symptom.

Drugs causing infertility

Alkylating agents (cycophosphamide , mechlorethamine, procarbazine, chlorambucil)

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9- Secondary malignancies

Secondary cancers induced by chemotherapy and radiation are a serious long term complication.

acute nonlymphocytic leukemia or myelodysplastic syndrome has been reported following successful treatment of hodgkin lymphoma, acute leukemia, non- hodgkins lymphomas, multiple myeloma, breast cancer, and advanced ovarian cancer.

Solid tumors as secondary malignancies occur more commonly after treatment with radiation than with chemotherapy.

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Drugs causing secondary malignancies

Miscellaneous agents (hydroxyurea).

Alkylating agents (cyclophosphamide , mechlorethamine, procarbazine and chlorambucil)

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10- liver toxicity

1- elevation liver function tests

Antimetabolites ( gemcitabine) ,

Antimicrotubule agents ( irinotecan and topotecan)

Alkylating agents ( chlorambucil)

Immune therapy (interferon alfa)

Biologically-directed therapies ( bexarotene, imatinib ,tretinoin and Gemtuzumab)

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2- jaundice and hyperbilirubinemia

Antimetabolites ( 6- mercaptopurine)

3- cirrhosis and portal fibrosis

Antimetabolites (methotrexate)

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4- hepatic veno-occlusive disease

Alkylating agents (busulfan)

Biologically-directed therapies ( Gemtuzumab )

Hepatic veno-occlusive disease is treated by defibrotide.

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11- Nephrotoxicity

Alkylating agents ( carmustine , cisplatin, ifosfamide)

Immune therapy (interleukin-2)

Antimetabolites (methotrexate).

Amifostine is used to decrease risk of nephrotoxicity of chemotherapy.

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12- hemorrhagic cystitis (HC)

Drug causing hemorrhagic cystitis

Alkylating agents (cyclophosphamide and ifosfamide).

For prevention HC hydration and 2- mercaptoethane sulfonate ( Mesna) are needed.

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13- Neurotoxicity

1- Cerebellar toxicity

antimetabolites (cytarabine)

2- Peripheral neuropathy

Antimicrotubules (vincristine, vinblastine, vinorelbine, paclitaxel and docetaxel)

Alkylating agents (cisplatin , oxaliplatin and procarbazine )

Biologically-directed therapies (bortezomib)

Glutathione , magnesium , calcium and vitamin E being used for prevention of neuropathies.

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3- seizures

Alkylating agents (busulfan)

4- Confusion, somnolence and disorientation

Alkylating agents (ifosfamide )

Miscellaneous agents ( interleukin-2)

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14- pulmonary toxicity

Drug causing pulmonary toxicity

1- Dyspnea

Antimetabolites ( Gemcitabine, Azacitidine)

2- Pulmonary fibrosis

Miscellaneous agents (bleomycin)

Alkylating agents (busulfan , chlorambucil ,carmustine and chlorambucil)

biologically-directed therapies (Gefitinib)

Antimetabolites ( fludarabine)

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15- Cardiotoxicity

Myocardial ischemic symptom ( flurouracil)

Cardiac toxicity

Antimicrotubules ( paclitaxel ,daunorubicin, doxorubicin, idarubicin, mitoxatrone)

Biologically-directed therapies(trastuzumab).

Liposomal form of anthracene reduce risk od cardiotoxicity. And also can be reduced by use cardioprotective ( Dexrazoxane).

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16- Tumor lysis syndrome

Clinical characterized by rapid development of hyperuricemia; hyperkalemia; hyperphosphatemia, hypocalcemia and acute renal failure.

Drugs causing tumor lysis syndrom

Biologically-directed therapies(Gemtuzumab and Rituximab)

Antimetabolites(Cytarabine , fludarabine)

Miscellaneous agents (Hydroxyurea)

Hyperuricemia is treated by allopurinol or Rasburicase

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17- Extravasation injury

Vesicants are antineoplastic agents that may cause sever tissue damage if they escape from the vasculature.

These agents include

Antimicrotubule agents

Anthracyclines ( Doxorubicin, Daunorubicin, Idarubicin and Epirubicin)

Vinca alkaloids ( vinblastine, vincristine and vinorelbine) Taxanes ( Docetaxel and paclitaxel) .

Miscellaneous agents (mitomycin C)

Alkylating agent (mechlorethamine)

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For extravasation vesicants, one of the most important interventions is the application of ice packs to the affected area. One exception this rule is the vinca alkaloids, which are better managed with application of heat.

Sodium thiosulfate is used to treat mechlorethamine extravasations and hyaluronidase can improve the outcome after extravasation of vinca alkaloids, etoposide, and taxanes.

Topical application of dimethyl sulfoxide may be an effective method for managing anthracycline and mitomycin extravasations.

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