Anti-Toxicity Drugs Used in Cancer Terapy

ANTI-TOXICITY DRUGS USED IN CANCER THERAPY


ANTI-TOXICITY DRUGS USED IN CANCER THERAPY

TOXICITIES OF ANTI-CANCER DRUGS:

1. Toxicities of alkylating agents:

  • All alkylating agents are myelosuppressive, pulmonary fibrosis, sterility & secondary leukemias (less common with cyclophosphamide).
  • In high dose, all alkylating agents cause veno-occlusive disease in liver (reversed by defibrotide).

Alkylating agents

Distinctive toxicity

Cyclophosphamide

Alopecia, hemorrhagic cystitis, SIADH

Nitrosoureas & ifosfamide

Renal failure

Nitrosoureas &  mechlorethamine

Local irritation & damage – Due to strong vesicant properties

Ifosfamide

Hemorrhagic cystitis, SIADH

Busulfan

Pulmonary fibrosis, hyperpigmentation, adrenal insufficiency

Procarbazine

Secondary leukemia, disulfiram-like-reaction, behavioral changes, CNS depression

Cisplatin

Emesis, nephrotoxicity, peripheral sensory neuropathy, ototoxicity

2. Toxicities of anti-metabolites:

  • All antineoplastic antimetabolites cause bone marrow suppression

Anti-metabolites

Distinctive toxicity

6-MP & 6-TG

Hepatotoxicity

Methotrexate

Mucositis, hepatotoxicity

5-FU

Hand and foot syndrome, neurotoxicity

Capecitabine

Hand and foot syndrome, Hyperbilirubinemia

Cytarabine

Cerebellar ataxia

Fludarabine

Arthralgia

Gemcitabine

Diarrhea

3. Toxicities of natural anticancer drugs:

  • All natural anticancer products can cause bone marrow suppression except bleomycin & vincristine.

Natural anticancer drugs

Distinctive toxicity

Bleomycin

Pulmonary fibrosis (Marrow sparing)

Anthracyclines

Cardiotoxicity

Paclitaxel

Peripheral neuropathy & hypersensitivity

Docetaxel

Peripheral neuropathy, Fluid retention

Irinotecan

Diarrhea

Vincristine

Peripheral neuropathy (Marrow sparing), SIADH.

4. Toxicities of hormonal agents:

Hormonal agents

Distinctive toxicity

Flutamide

Hot flushes, liver dysfunction

SERMs

Menopausal symptoms, fluid retention, thromboembolism, increased incidence of endometrial cancer

Progestins

Fluid retention

Corticosteroids

Fluid retention, hypertension, diabetes, increased susceptibility to infections

GnRH agonists

Transient flare-up reaction, hot flushes, impotence, gynecomastia, osteoporosis

Aminoglutethimide

Adrenal insufficiency, myelosuppression, rash

Aromatase inhibitors

Fatigue, hot flushes, arthralgia

TREATMENT:

Anti-toxicity drugs for anti-cancer drugs:

Anti-toxicity drug

Mechanism

Indications

Allopurinol

Inhibit xanthine oxidase Prevent hyperuricemia from tumor lysis syndrome

Rasburicase

Recombinant urate oxidase Prevent hyperuricemia from tumor lysis

Mesna (Sodium 2-mercapto ethane sulfonate)

Neutralizing agent Prevent hemorrhagic cystitis (due to ifosfamide) with high dose cyclophosphamide.

Leucovorin

Replete tetrahydrofolic acid Rescue after high dose methotrexate

Amifostine

  Prevent radiation-induced xerostomia & Cisplatin-induced nephrotoxicity.

Dexrazoxane

Iron-chelator Prevent cardiotoxicity due to anthracyclines

Palifermin

Keratinocyte growth factor Prevent mucositis following chemotherapy

Pilocarpine

Cholinergic agonist Radiation-induced xerostomia

Pamidronate & Zolendronate

Bisphosphonates Hypercalcemia of malignancy

Epoetin-alpha & Darbopoetin-alpha

Erythropoietin Anemia

Filgrastim & PegFilgrastim 

Sargramostim

G-CSF & GM-CSF respectively Febrile neutropenia prophylaxis

Oprelvekin

IL-11 Thrombocytopenia

Ondansetron, Granisetron & Palonosetron

Ondansetron – 5-HT antagonist

 

Granisetron & Palonosetron – 5HT3 antagonist

Nausea & vomiting

Aprepitant & Fosaprepitant 

NK-1 antagonist Cisplatin-induced delayed vomiting

Exam Important

  • Drugs used to prevent toxicity of anti-cancer drugs include allopurinol, rasburicase, mesna, leucovorin, amifostine, dexrazoxane, palifermin, pilocarpine, pamidronate, filgrastim, sargramostim, ondansetron, granisetron, aprepitant& fosaprepitant.
  • Anticancer drugs having highest emetogenic potential is cisplatin.
  • Antineoplastic agent is an antifolate drug is Methotrexate.
  • Aprepitant Fosaprepitant are NK-1 antagonists used for cisplatin-induced delayed vomiting.
  • Ondansetron is a 5-HT antagonist useful for treating vomiting.
  • Granisetron & Palonosetron are 5HT3 antagonist.
  • Sargramostim is a GM-CSF used for treating anti-cancer drug-induced neutropenia.
  • Pamidronate is 
  • Mesna is sodium 2-mercapto ethane sulfonate, is useful for preventing hemorrhagic cystitis (due to ifosfamide).
  • Vincristine causes peripheral neuropathy & SIADH.
  • Anticancer drug bleomycin causes pulmonary fibrosis.
  • 5-FU is an anticancer drug result in hand & foot syndrome.
  • Cisplatin is responsible for emesis & nephrotoxicity.
  • Procarbazine produces disulfiram-like-reaction.
  • Busulfan can result in pulmonary fibrosis.
  • Cyclophosphamide can cause hemorrhagic cystitis.
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