To define the target treatment groups: Monoclonal antibodies Cancer vaccines TKI Hematopoetic growth factors
To Know the indication, contraindication and Drug-Drug interactions of each target treatment group.
Monoclonal Antibodies Approved by the EMA and FDA for Therapeutic Use (status 2013)
Drug Name Target Therapeutic Indications Muromonab CD3 Transplantation rejection Satumomab TAG-72 Detection of colorectal and ovarian cancers (non-therapeutic) Nofetumomab Carcinoma- Diagnostic imaging of small-celllung cancer associated antigen (non-therapeutic) Capromab Tumor surface Detection of prostate adenocarcinoma antigen PSMA (non-therapeutic) Arcitumomab Human CEA Detection of colorectal cancer (non-therapeutic) antigen -Daclizumab CD25 (a chain of Reversal of transplantation rejection - Basiliximab IL2 receptor) Drug Name Target Therapeutic Indications Rituximab CD20 Non-Hodgkin’s lymphoma, Chronic lymphocytic leukemia, Rheumatoid arthritis Trastuzumab HER-2 Breast cancer, Metastatic gastric or gastro esophageal junction, adenocarcinoma Gemtuzumab CD33 Acute myeloic leucemia (AML) ozogamicin Ibritumomab CD20 Non-Hodgkin’s lymphoma tiuxetan Alemtuzumab CD52 B-cell chronic lymphocytic leukemia
Bevacizumab VEGF Metastatic colorectal cancer, Non-small cell lung cancer, Metastatic breast cancer, Glioblastoma multiforme , Metastatic renal cell carcinoma Cetuximab EGFR Head and neck cancer, Colorectal cancer
Panitumumab EGFR Metastatic colorectal carcinoma Drug Name Target Therapeutic Indications
Eculizumab Complement C5 Paroxysmal nocturnal hemoglobinuria
-Trastuzumab HER2 Breast cancer emtansine - Pertuzumab
-Obinutuzumab CD20 CLL - Ofatumumab
Brentuximab CD30 Hodgkin lymphoma (HL), systemic anaplastic large cell lymphoma (ALCL)
Ipilimumab CTLA-4 Melanoma
Denosumab RANKL Prevention of SREs in patients with bone metastases from solid tumours Drug Name Target Therapeutic Indications
Abciximab GPIIb/IIIa High risk angioplasty(prevention of blood clots)
Imiciromab Human cardiac Myocardial infarction imaging agent (non- myosin therapeutic)
Sulesomab NCA90 Diagnostic imaging forosteomyelitis (non- therapeutic0
Infliximab TNFα Crohn’s diseaseUlcerative colitis, Rheumatoid arthritisAnkylosing spondylitis ,Psoriatic arthrits Plaque psoriasis Palivizumab F-protein of RS Respiratory Syncytial Virus (RSV) virus Votumumab Cytokeratintumo Detection of carcinoma of thecolon or rectum r-associated (non-therapeutic) antigen Drug Name Target Therapeutic Indications
Adalimumab TNFα Rheumatoid arthritis, Juvenile idiopathic arthritis, Psoriatic arthritis, Ankylosing spondylitis ,Crohn’s disease, Plaque psoriasis Efalizumab CD11a Psoriasis
Omalizumab IgE Asthma
Tositumomab CD20 Non-Hodgkin’s lymphoma and iodine 131 tositumomab Fanolesomab CD15 Imaging of equivocal appendicitis (non- therapeutic) Natalizumab VLA-4 Multiple sclerosis (relapsing)Crohn’s disease Drug Name Target Therapeutic Indications
Catumaxomab EpCAM Head and neck cancer
Ranibizumab VEGF-A Neovascular (wet) age-related macular degeneration, Macular edema following retinalvein occlusion Certolizumab TNFa Crohn’s diseaseRheumatoid arthritis pegol
Canakinumab IL-1ß Cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome and Muckle-Wells syndrome Catumaxomab EpCAM and Malignant ascites in patients with EpCAM-positive CD3 carcinomas Golimumab TNFa Rheumatoid arthritisPsoriatic, arthritisAnkylosing spondylitis Drug Name Target Therapeutic Indications
Tocilizumab IL-6 receptor Rheumatoid arthritis
Ustekinumab IL-12 / IL-23 Plaque psoriasis
Besilesomab NCA-95 Diagnosis of inflammation / infection sites via scintigraphic imaging (non-therapeutic)
Belimumab BLyS Systemic lupus erythematosus (SLE)
Raxibacumab Bacillus anthracis Prevention and treatment of inhalation anthrax protective antigen Contraindications / Cautions
caution in elderly patients caution if cardiovascular disease or history caution if angina or history caution if pulmonary disease caution if high tumor burden caution if HBV carrier caution if infection, latent or chronic
Types of Cancer Vaccines
Preventive or Prophylactic
• HPV • HBV
Treatment
• For metastatic prostate cancer What cancer preventive vaccines are approved FDA?
Human papillomavirus (HPV) vaccines. Persistent infections with high risk HPV types can cause cervical cancer, anal cancer, orpharyngeal cancer, and vaginal, vulvar, and penile cancers.
Three vaccines are approved by the US (FDA) to prevent HPV infection: • Gardasil • Gardasil 9 • Cervarix What cancer preventive vaccines are approved FDA?
Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to Liver cancer.
Two vaccines are approved by the US (FDA) to prevent HBV infection: • Engerix-B • Recombivax HB Active Clinical Trials of Cancer Active Clinical Trials of Cancer Treatment Vaccines by Type of Preventive Vaccines by Type of Cancer: Cancer:
•Lung Cancer •Cervical Cancer •Non-Hogkin Lymphoma •Solid Tumors •Prostate Cancer •Breast Cancer •Bladder Cancer •Brain Cancer •Ovarian Cancer •Solid Tumor •Pancreatic Cancer •Multiple Myloma •Melanoma •Leukemia Contraindications for Adult Vaccine:
• Hepatitis B vaccine: Sensitivity to yeast.
• HPV vaccine: Pregnancy and anaphylactic shock to previous dose. is a therapeutic Cancer vaccine for the treatment of solid tumors that is currently under clinical development by Recombio, an international public-private consortium with the participation of the Center of Molecular Immunology at Havana, Cuba (CIM) and researchers from Buenos Aires University and National University Of Quilmes In Argentina.
Racotumomab triggers an immune response against the tumor antigen N-glycolil (NGcGM3), a type of ganglioside present on the cell surface of malignant cells from lung and breast, melanoma.
Racotumomab is administered in patients who have previously received the oncospecific treatment established in the oncological therapeutic standards (surgery, chemotherapy and radiation therapy). A Racotumomab solution is administered by intradermal injection every 14 days for the first 2 months (5 doses), followed by monthly booster doses.
Racotumomab has been approved in two countries, Argentina and Cuba, for the treatment of recurrent or advanced NSCLC, or NSCLC independent of the disease stage when no other standard therapy can be administered.
(FDA)-Approved Tyrosine Kinase Inhibitors (TKIs)
Drug Name Target Therapeutic Indications
Dasatinib BCR-ABL, SRC Chronic myeloid leukemia, acute lymphocytic (Sprycel) family, c-KIT, leukemia PDGFR Erlotinib (Tarceva) EGFR Non-small cell lung cancer, pancreatic cancer
Gefitinib (Iressa) EGFR Non-small cell lung cancer
Imatinib (Gleevec) BCR-ABL, Acute lymphocytic leukemia, chronic myeloid c-KIT, leukemia, gastrointestinal stromal tumors, PDGFR hypereosinophilic syndrome, systemic mastocytosis
(FDA)-Approved Tyrosine Kinase Inhibitors (TKIs)
Drug Name Target Therapeutic Indications
Lapatinib (Tykerb) HER2/neu, Breast cancer with HER2/neu overexpression EGFR Nilotinib (Tasigna) BCR-ABL, c- Chronic phase or accelerated Ph- positive CML for KIT, PDGFR patients resistant/intolerant of prior imatinib therapy
Sorafenib (Nexavar) BRAF,VEGF Renal cell cancer, hepatocellular carcinoma REGFR,PD GFR Sunitinib (Sutent) VEGFR,PD Renal cell cancer, gastrointestinal stromal tumor GFR, c- KIT,FLT3 Drug interactions with the tyrosine kinase
Available HGFs are:
G-CSF GM-CSF TPO EPO CSF Therapeutic Indications
• EPO was beneficial in raising the hemoglobin levels of patients with MDS. Also, EPO is more likely to be useful in nontransfused anemic patients as opposed to those who have already begun transfusions.
• G-CSF or GM-CSF to increase the absolute neutrophil count of neutropenic patients with MDS, have a special role in the setting of bone marrow transplantation (BMT).
• In leukemic patients, CSFs have been used to prime patients, theoretically lining up blasts in the same cell phase so that chemotherapy will be more effective.
• TPO mimetics (romiplostim and eltrombopag) have demonstrated efficacy in raising platelet counts in ITP patients. They have been used in both pre and postsplenectomy patients.
Other Types of Biotherapy: (Interleukins and Cytokines)
Interleukins Principal Source Primary Activity
co-stimulation of APCs and T cells, macrophages and other antigen presenting cells IL1-α and -β inflammation and fever, acute phase (APCs) response, hematopoiesis
proliferation of B cells and activated T IL-2 activated Th1 cells, NK cells cells, NK functions
growth of hematopoietic progenitor IL-3 activated T cells cells
B cell proliferation, eosinophil and mast cell growth and function, IgE and IL-4 Th2 and mast cells class II MHC expression on B cells, inhibition of monokine production
IL-5 Th2 and mast cells eosinophil growth and function Interleukins Principal Source Primary Activity
hematopoietic and thymopoietic IL-9 T cells effects
synergisitc hematopoietic and IL-11 bone marrow stromal cells thrombopoietic effects
regulates the growth and IL-14 T cells and malignant B cells proliferation of B cells
eosinophils, CD8+ T cells, lymphocytes, IL-16 chemoattractant for CD4+ cells epithelial cells
antiviral effects, induction of class macrophages, neutrophils and some I MHC on all somatic cells, INF-α and -β somatic cells activation of NK cells and macrophages
Hormone Therapy
Hormone Therapy for Breast Cancer
Some types of breast cancer are affected by hormones in the blood. ER-positive and PR-positive breast cancer cells have receptors that attach to estrogen, which helps them grow. There are different ways to stop estrogen from attaching to these receptors. Hormone therapy is a form of systemic therapy, meaning it reaches cancer cells anywhere in the body and not just in the breast. It's recommended for women with hormone receptor-positive (ER-positive and/or PR-positive) breast cancers, but it does not help women whose tumors are hormone receptor-negative (both ER- and PR-negative).
Treatments that lower estrogen levels
Aromatase inhibitors (AIs) are drugs that stop estrogen production. Letrozole (Femara) Anastrozole (Arimidex) Exemestane (Aromasin) Drugs that block estrogen receptors
Tamoxifen; This drug blocks estrogen receptors in breast cancer cells. Toremifene (Fareston) is another SERM that works in a similar way, but it is used less often and is only approved to treat metastatic breast cancer. Fulvestrant is a drug that blocks estrogen receptors and also eliminates them temporarily.
Ovarian ablation
For pre-menopausal women, removing or shutting down the ovaries (ovarian ablation), which are the main source of estrogens, effectively makes them post-menopausal. This may allow some other hormone therapies, such as AIs, to work better. Oophorectomy: Surgery is done to remove the ovaries. This is a form of permanent ovarian ablation. Luteinizing hormone-releasing hormone (LHRH) analogs: These drugs are used more often than oophorectomy. They stop the signal that the body sends to ovaries to make estrogen, which causes temporary menopause. Less common types of hormone therapy Some other types of hormone therapy were used more often in the past, but are rarely given now. These include: Megestrol acetate (Megace), a progesterone-like drug Androgens (male hormones) High doses of estrogen These might be an option if other forms of hormone therapy are no longer working, but they can often cause side effects.
Hormone Therapy for Prostate Cancer
Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy. Luteinizing hormone-releasing hormone (LHRH) agonists (also called LHRH analogs or GnRH agonists) are drugs that lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes called chemical castration or medical castration because they lower androgen levels just as well as orchiectomy. Leuprolide (Lupron, Eligard) Goserelin (Zoladex) Triptorelin (Trelstar) Histrelin (Vantas)
Hormone Therapy for Prostate Cancer LHRH antagonist Degarelix (Firmagon) is an LHRH antagonist. CYP17 inhibitör LHRH agonists and antagonists can stop the testicles from making androgens, but other cells in the body, including prostate cancer cells themselves, can still make small amounts, which can fuel cancer growth. Abiraterone (Zytiga) blocks an enzyme called CYP17, which helps stop these cells from making androgens. Hormone Therapy for Prostate Cancer Drugs that stop androgens from working Anti-androgens Androgens have to bind to a protein in the prostate cell called an androgen receptor to work. Anti-androgens are drugs that bind to these receptors so the androgens can’t. Flutamide (Eulexin) Bicalutamide (Casodex) Nilutamide (Nilandron) They are taken daily as pills. Enzalutamide (Xtandi) is a newer type of anti-androgen
Hormone Therapy for Prostate Cancer Estrogens (female hormones) were once the main alternative to orchiectomy for men with advanced prostate cancer. Ketoconazole (Nizoral), first used for treating fungal infections, blocks production of certain hormones, including androgens, much like abiraterone. It's most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer working. References:
http://onlinelibrary.wiley.com/doi/10.3322/canjclin.46.3.165/full
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagem ent/hematology-oncology/use-of-hematopoietic-growth-factors/#top
https://www.cancer.gov/about-cancer/causes-prevention/vaccines- fact-sheet
http://www.vaxira.com/en_vaxira.html#supervivenciaGlobal
https://www.oncolink.org/cancer-treatment/therapies/targeted/part- one-introduction-to-small-molecule-tyrosine-kinase-inhibitors