Side Effects of Cancer Treatments : Chemotherapy

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Side Effectsof Cancer Treatments Chemotherapy

• ??? Surachat Chakrapee-Sirisuk

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ONCOLOGYCancer biology
Tumor growth and detection
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• TREATMENT RESULT
• OBJECTIVE Measurable
• Evaluable SUBJECTIVE Complete
  Response CR - Clinical
  cCR - Pathological pCR Partial
  Response PR Overall Response
  (CR PR) Minimal Response Stable
  Disease Progressive Disease

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• CHEMOTHERAPY Paul Ehrlich in vivo rodent
  model systems to develop antibiotics
• MUSTARD GAS
• 1943 Yale Cancer Center hematologic
  neoplasms, including Hodgkin's disease
• lymphocytic lymphomas
• PP6 DeVita 2001

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• CANCER CHEMOTHERAPY
• - Highly toxic- Narrow therapeutic index-
  Error in dosage or dose adjustment may be
  lethal- Requires a higher level of
  pharmacologic understanding than any other
  subspecialty of internal medicine- Optimal
  dose-intensity- Route and schedule of
  administration- Safe-dosage range single
  agent combination, Drug interactions-
  Dose adjustment to accommodate organ
  dysfunction.- Awareness of incidence and course
  of potentially life- threatening toxicity.

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• LIMITATIONS OF CANCER TREATMENT
• 1. Inability to determine precisely which
  cancers have metastasized at the time of
  diagnosis2. Inability to detect minimal
  residual disease after apparently successful
  treatment3. Inability to escalate doses of
  effective anticancer drugs to the high end of
  the dose-response curve4. Hurdle presented by
  the unexpected expression of MDR (MultiDrug
  Resistance)5. Inability to measure the
  moment-to-moment impact of treatment on cancer
  cells.

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ONCOLOGYPrinciples of chemotherapy
Action sites of cytotoxic agents

• AntibioticsAntimetabolites

S (2-6h)
G2 (2-32h)
Vinca alkaloids
M (0.5-2h)
Mitotic inhibitors
Taxoids
Alkylating agents
G1 (2-?h)
Cell cycle level
G0
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ONCOLOGYPrinciples of chemotherapy
Drug resistance

• EXTRACELLULAR INTRACELLULAR

PGP170 ATP
Drug
ATP
Drug
Plasma Membrane
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• Role of chemotherapy
• 1. Induction Rx. for advanced disease
• 2. Adjunct to local methods of Rx.
• 3. Primary Rx. for some localized disease, in
  whom local forms of therapy by themselves are
  inadequate
• 4. Direct Instillation into sanctuary sites or by
  site-Directed Perfusion of specific regions of
  the body directly affected by the cancer.
• PP6 DeVita 2001

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ONCOLOGYPrinciples of chemotherapy
Aim of combination therapy

• INCREASED EFFICACY

SAFETY
ACTIVITY
Different mechanisms of action
Compatible side effects Different mechanisms
of resistance
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• TOXICITY
• Myelosuppression drug with minimal marrow
  suppression Lower the dosage Hematopoietic
  Growth Factor G-CSF, GM-CSF, IL-3,
  etc. Autologous (allogeneic) bone marrow support
  Bone marrow harvesting Peripheral stem
  cell harvesting

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• G-CSF (Neupogen), GM-CSF
• Procrit (Epoetin alfa), Eprex
• Neumega (Oprelvekin) platelet growth factor
• Keratinocyte Growth factor (KGF)
• Stem Cell Growth Factor

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• Antiemetics
• 5-HT3 receptor antagonist
• Ondansetron (Zofran)
• Granisetron (Kytril)
• (Novoban)
• Dolasetron(Anzemet)

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ADVANCED HEAD NECK CANCER

• Amifostine (Ethyol)
• prospective random, n303
• RT (50-70 Gy, gt75 of both parotid glands were
  included) vs.
• RT and Amifostine
• (iv) 200mg/m2/d 15-30 min. before RT
• Acute Xerostomia (gradegt2) 70 v 51 (plt.0001)
• 50 grade II at 42Gy v 60 Gy (p.0001)
• 1-Y after grade gt2 57 v 34 (p.002)
• median saliva (no stimulation) 0.1 v 0.26 gm
  (p.04)
• NOT reduce grade III Mucositis
• Brizel et al. Int J Radiat Oncol Biol Phys
  1999 45147

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• Oncologic Drug Advisory Committee US.FDA. July
  1999
• Approved Ethyol (Amifostine)
• to decrease incidence of moderate to severe
  Xerostomia in post-operative radiation therapy
  of HeadNeck cancer whose RT port include a
  substantial portion of parotid glands

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Keratinocyte Growth factor (KGF)

• paracrine factor from mesenchymal cell in
  epithelium (member of FGF7)
• stimulate epithelial cell proliferation
  differentiation
• Promote fasten
• repair of Rx.-induced normal tissue damage
• given AFTER RT, CmT significantly
  decrease oral GI toxicity no sig. effect on
  Sq. cell CA
• phase II Ongoing

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Interferon (IFN)

• SIDE EFFECTS
• Acute fever, chill, malaise, arthralgia
• Chronic fatigue, myalgia, headache, anorexia,
  weight loss, insomnia hypersomnia, minor
  depression, major depression, impair cognitive
  executive function, motor speed and dexterity,
  diminish sexual interest or function,
  reversible hematologic and hepatic change,
  hypothyroidism, hyperthyroidis, (autoantibodies)

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Improved Safety profile versus bolus 5-FU/LV
(all grades)
Patients ()
Treatment-related AEs
100 80 60 40 20 0
Capecitabine (n993) Bolus 5-FU/LV (n974)






Diarrhea Stomatitis Hand-foot Neutropenia
Nausea/ Alopecia syndrome vomiting
plt0.001 Laboratory value
Scheithauer W et al. Ann Oncol 200314173543
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• Unsound Methods of Cancer Treatment
• Alivizatos therapy (greek cancer cure),
  Antineoplastons, Bamfolin, Beard method,
  Bonifacia anticancer goat serum, Cancer-lipid
  concentrate, Carcin and neo-carcin,
  Carzodelin, C.N.T., CH-23, Chase dietary
  method, Collodaurim and bichloracetic acid,
  Chaparral tea, Clam extracts (mercenene),
  Contreras method, Cresson method, Crofton
  immunization, Cytec lung cancer screening,
  Diamond carbon compound, Dimethyl sulfoxide
  (DMSO), Dotto electronic reactor, Ferguson
  plant products, Fonti method, Francis diet,
  Fresh cell therapy, Frost method, Gerson
  method, Glover serum, Grape diet,
  Hemacytology index, Hett cancer serum, Hill
  Hadley vaccine, Hoxsey method,
  Immunoaugmentative therapy (IAT), Iscador,
  Issels combination therapy, KC-555, Kanfer
  handwriting test, Kelly malignancy index,
  Koch anti-toxin, Krebiozen, Laetrile
  (amygdalin, vitamin B17), Lows method,
  Macrobiotic diet, Makari intradermal cancer
  test, Metabolic therapy, Mucorhicin,
  Multiple enzyme therapy, Orgone energy
  devices, Polonine, Psychic surgery,
  Revici method, Spears hygenic system ,
  Ultraviolet blood irradiation