Chemo-, hormonal-, and targeted therapy Dr. Judit Toth Department of Oncology Medical University of Debrecen.

Chemo-, hormonal-, and targeted therapy

Dr. Judit Toth Department of Oncology

Medical University of Debrecen

Chemotherapy is used for a variety of purposes:

• To cure a specific cancer; • To control tumor growth when cure is not possible; • To relieve symptoms (such as pain) • To shrink tumors before surgery or radiation therapy; • To destroy microscopic cancer cells that may be present

after the known tumor is removed by surgery (called adjuvant therapy). Adjuvant therapy is given to prevent a possible cancer micro-metastases

Chemotherapy Terms

• Adjuvant chemotherapy • Neoadjuvant chemotherapy • Palliative chemotherapy

Neoadjuvant Therapy : Definition

• Neoadjuvant therapy, also named primary therapy or preoperative therapy, is a systemic treatment delivered before the local treatment, such as surgery and/or radiotherapy

Neoadjuvant Therapy

• Rationale– Decrease in the tumor size leading to a more

conservative surgery, and facilitating surgical procedures– To eradicate micrometastases

Neoadjuvant Therapy

• Rationale and Indication– Patients with locally advanced disease– Decrease in the tumor size leading to a more conservative surgery,

and facilitating surgical procedures– To eradicate micrometastases

• Treatment– Chemotherapy– Hormonotherapy– Targeted therapy

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Cancer and Treatment StrategiesTwo different approachesTwo different approaches

– Local disease Local disease curative treatment• To treat the primary tumor ( local lymph nodes)

• To eradicate micrometastases = adjuvant therapy

– Advanced or metastaticAdvanced or metastatic disease disease• Very occasionally to cure!

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Cancer and Treatment Strategies– Local disease Local disease

– Advanced or metastatic disease Advanced or metastatic disease palliative treatment• Advanced disease = unresectable tumor or large regional lymph node involvement

• Metastases

• To controll signs and symptoms of disease• Improve quality of life• Prolong life

• Very occasionally to cure!

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ChemotherapyClassification (I)

Family Molecules Targets

Anthracyclines-

Anthracenediones

Doxorubicin

Epirubicin

Idarubicin

Mitoxantrone

Topoisomerase II

DNA

Topo-I Inhibitors Irinotecan

Topotecan

Topoisomerase I

DNA

Antimetabolites Fluorouracil

Methotrexate

Mercaptopurine

Fludarabine

Cytarabine

Gemcitabine

Capecitabine

Puric and pyrimidic bases

ChemotherapyClassification (II)

Family Molecules Targets

Alkylating agents Cyclophosphamide

Melphalan

Ifosfamide

Busulfan

DNA

Spindle inhibitors Vinorelbine

Vincristine

Vindesine

Vinblastine

Tubuline

Docetaxel

Paclitaxel

Platinum salts Carboplatine

Cisplatine

Oxaliplatine

DNA

„saturation bombing” =chemotherapy?

Side effects of chemotherapy

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Hair loss: why does it occur?

• Chemotherapy drugs are powerful medications that attack rapidly growing cancer cells.

• Unfortunately, these drugs also attack other rapidly growing cells in body.– including those in hair roots, eyelash, eyebrow,

armpit and other body hair also falls out. Hair usually begins falling out one to three weeks after starting treatment and re-grows three to 10 months after treatment ends.

Side effects of chemotherapy

• Hair loss• Myelo-suppression

Myelosuppression

• Bone marrow suppression is a common side effect of chemotherapy that is characterized by a decrease in blood cell production.

• Myelosuppression can result in the decrease in one, two or all three types of blood cells.– Anemia– Thrombocytopenia– Neutropenia

• Different kinds of growth factors can be used to target the reproduction of red blood cells, white blood cells or platelets.

Side effects of chemotherapy

• Hair loss• Myelo-suppression

• Nausea, Vomiting– Prevention is best defense!

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The vomiting centre (VC) in the medulla oblongata, the chemoreceptor trigger zone (CTZ) in the area postrema (AP) on the caudal margin of the IVth ventricle,

aprepitant (Emend®) 

dolasetron (Anzemet®) 

granisetron (Kytril®) 

ondansetron (Zofran®)

palonosetron (Aloxi®) 

proclorperazine (Compazine®) p

romethazine (Anergan®),(Phenergan®)

lorazepam (Ativan®) 

metoclopramide (Reglan®)

dexamethasone (Decadron®) 

famotidine (Pepcid®)

ranitidine (Zantac®) 19

Vomiting and nausea

• Certain chemotherapy drugs are more likely than are others to cause nausea and vomiting:

• Cisplatin• Carboplatin• Oxaliplatin• Cyclophosphamide (Cytoxan)• Doxorubicin or epirubicin• Dacarbazine

• Anti-nausea medications are typically given before treatment !!!

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Side effects of chemotherapy

• Cardiotoxicity and cardiomyopathy – Fortunately, heart disease associated with

chemotherapy is relatively rare. (Not all chemotherapy drugs carry the potential side effect of heart damage and often temporary :Doxorubicin, 5-FU)

– some newer anti-cancer treatments — such as trastuzumab (Herceptin) for breast cancer — may cause heart damage.

Peripheral neuropathy

• Peripheral neuropathy is caused by damage to nerves, most commonly the sensory nerves (nerves that sense touch, heat or pain).– Pain, burning or tingling in fingers, toes, hands and

feet – Loss of sensation to touch– Muscle weakness and balance problems– Decreased reflexes

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Skin side effects

• Allergy• Hand foot syndrome (HFS)

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Nephrotoxicity

• Strong nephrotoxic anticancer agents are: cisplatin and ifosfamide:– cause necrosis of the proximal tubules

• methotrexate:– deposits and blocks the tubule

Sufficient renal function is important before administration of the anticancer drug !

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Sharp shooter = targeted therapy?

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Examples of targets being investigated in cancer treatment

Examples of targeted anticancer therapies approved or in development

General target Specific target Agent or approach

Signal transduction Growth factor receptorsErbB1 (EGFR)ErbB2 (HER2)ErbB1 and ErbB2

Bcr-AblRasRaf

Erlotinib, gefitinibTrastuzumabTyverbImatinibFarnesyl transferase inhibitorsAntisense oligonucleotides

Angiogenesis andmetastasis

VEGFR2VEGF

Matrix metalloproteinasesIntegrins

SunitinibBevacizumabPazopanibAE-941Humanised LM609 mAb

Tumour suppressorgene

p53 p16

Gene therapyGene therapy

Cell-cycle control Cyclin-dependent kinases mTOR

Flavopiridol Temsirolimus (CCI779)Everolimus

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Endocrine Therapy

Endocrine Therapy

Less toxic effective method of disease control

Hormone responsive disease: 70% of breast cancer patients (ER/PR+) 90% of prostatic cancer patients Endometrium carcinoma ~1% of other malignancies (Lung, renal cancer)

Hormonal therapy

• The signals from the hormonal receptors "turn on" growth in cells.

• Inhibitors of hormone synthesis:– Analogs of gonadotropin-releasing hormone (GnRH) can

be used to induce a chemical castration– Aromataze inhibitors(letrozol, anastrazol,examestane)

• Hormone receptors antagonists:– Selective Estrogen Receptor Modulators(tamoxifen)– Antiandrogens(nilutamid, flutamide)

Thank you if you are still awake