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Principles of Cancer Therapy
Jeffrey T. Reisert, DO
University of New England
Physician Assistant Program
March 4, 2010
Contact Information
Jeffrey T. Reisert, DO
Tenney Mountain Internal Medicine
16 Hospital Rd.
Plymouth, NH 03264
603-536-6355
603-536-6356 (fax)
[email protected]
Case study
You are on the surgical service asked to
evaluate a patient with a “GI bleed”
 67 y/o male with no prior endoscopies
 Evaluation reveals a weight loss, heme
positive stools.
 Exam is otherwise unremarkable.

Case study questions
What lab w/u is needed.
 What testing is required?

–
–

Lab
Other evaluations
What next?
Outline of Program
Surgery
 Radiation therapy
 Chemotherapy
 “Other” treatments for cancer
 Overview of some specific cancers
 Palliative care

Overview of Treatment
Requires tissue diagnosis and staging
 Risk-Benefit ratio
 “Kill the cancer before the patient”
 “A chance to cut is a chance to cure.”
 Choice of a given therapy is based on type
of disease spread
 Cure vs........ palliation????

Surgery
Historically the first treatment available
 “If cancer is the answer, tissue is the issue!”
 Use includes diagnosis, staging, definitive
treatment
 Caution to avoid spread/Isolate tumor (i.e.:
testicular CA)

Surgical techniques
Aspiration-Fine needle-i.e.: Thyroid
 Needle biopsy-Core specimen
 Incisional biopsy-Remove part of large
tumor
 Excisional biopsy-Remove entire tumor
 Staging-i.e.: Exploratory lap in Hodgkin’s
lymphoma
 Reconstructive

More definitions

What do you call a liver biopsy????
Surgery considerations
Must take into account margin of resection,
lymph node status
 Cure is more likely in slow growing, local
tumors
 Palliation best for fast growing or metastatic
tumors when complications arise

–

i.e.: Bleeding, Obstruction, Pain
May need to integrate with chemotherapy
Adjuvant vs....... Neoadjuvant
Adjuvant-Treatment to eliminate non
detectable micrometastasis
 Neoadjuvant-Treatment before surgery to
increase success

–
–
i.e.: Breast CA
Rectal CA
Prophylactic surgery
Colon-Resection in familial polyposis,
ulcerative colitis
 Breast-Removal if risk for CA >20% in five
years???
 Orchiectomy-Undescended testicle.
Benefit?
 MEN II-Medullary thyroid cancer
 Skin-Actinic keratosis or dysplastic nevi

Radiation Therapy (RT.)-Goals
Local treatment
 Kill CA without damage to local tissues
 Allow interval for cellular repair

Radiation Therapy-Types
X-Rays-Focused beam from linear
accelerator
 Gamma rays-Uses radioactive isotopes

–

External beam-AKA Teletherapy
–

Cobalt 60, Cesium 137, Radium 126
i.e.: Head and neck tumor
Drink
–
i.e.: I131-Thyroid cancer
Radiation Therapy-Types II

Internal, Implantable-AKA Brachytherapy
-Origin of word is short
-Prostate or gyn tumors

Particle beam-Neutrons or protons-Tertiary
centers
Radiation Therapy-Methods
Induces biological damage to cells
 I.E.: DNA damage due to free radical
production

–
Breaks down DS of DNA
May be fatal at first cell division (Mitotic
cell death)
 May be fatal in a few hours (Inducing
programmed cell death (Apoptosis))

Radiation Therapy-Treatment
RT. kills a percentage of total tumor (not a
number of cells)
 Measured in Gray (Gy)=Amount of energy
absorbed
 1 Gy=1 Joule of energy per gram of tissue
 A Rad= 0.01 Gy [1 Gy = 100 RAD)

Radiation Therapy-Treatment
Planning
Can make it very safe
 Usually fractionated doses to increase safety
 i.e.: 180-300Gy per day, 5d per week, 5-8
weeks
 Implantable -“Seeds”- Prostate and GYN
CA
 Radionucleotides

–
–
Iodine 131 (Thyroid CA)
Strontium 89 (Palliate bony mets)
Radiation-Specific Uses

External Beam
–
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–
–
–
Hodgkin’s Lymphoma, Head and Neck tumors
Prostate, GYN, CNS, Skin
Breast
Palliation-Bony Mets
Urgent Use-Spinal cord compression, SVC
syndrome
Radiation TherapyComplications
Kills rapidly dividing cells
 Systemic-Fatigue

–
Driving to center/Rigorous schedule
Skin-Erythema
 GI-Mucositis or dry mouth, N/V,
Dysphagia, Diarrhea
 Myelosuppression-All 3 cell lines
 Cancer risk-Leukemia, Solid Tumors--Especially in Hodgkin’s disease

Chemotherapy Overview



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Major roll is treating metastatic disease
Curative or palliative intent
Kills percentage of total tumor (Not number of
cells)
99% reduction is a 2 log kill (1011 cells--->109
cells)
Kill requires adequate dose without toxicity
“Narrow therapeutic index”
Testing
Phase I-Test of safety (Not efficacy)
 Phase II-Tests activity against tumor

–
–

Typically in patients with advanced disease
“Guinea pigs” perhaps
Phase III-Compares drugs with other
treatments available
–
Large numbers of pts in multiple centers
Chemotherapy-Successes





Complete Remission (CR)-All malignancy gone
Partial Remission-50+% reduction with no new
disease
Stable
Progression-25% growth in size or new lesions
seen
Drugs can be ineffective at the start, or acquired
– Spontaneous mutations
Chemotherapy combinationsPrinciples
Each drug should have activity against
tumor
 Different mechanisms of action
 No cross resistance between agents
 Different toxicities

Chemotherapeutic agents
Included for completeness
 Don’t go crazy memorizing
 I have left this in but will not test on any
specifics.

Chemo examples

Antimetabolites-Pyrimidine like
–
MOA:
 False
substrate for biological pathway, incorporated
into DNA/RNA--->breaks)
–
Examples
5 Fluorouracil (5FU)-Breast, colorectal
 Others: Cytarabine (ara-C), Gemcitabine

–
ADR:Bone marrow suppression and GI
Chemo examples cont.

Antimetabolites-Purine like
–
MOA
 False
–
substrate for biological pathway
Examples
 Fludarabine,
–
6-Mercaptopurine (6MP)
ADR’s
 Myelosuppression
Chemo examples cont.

Class: Antimetabolites-Others
–
Methotrexate (MTX)
 MOA:
Inhibits dihydrofolate reductase preventing
purine synthesis
–
–
–
Use: ALL, bladder, breast, head/neck, HL)
ADR: BM and GI toxicity
Hydroxyurea
 CML,
Essential thrombocytosis
Chemo examples cont.

Plant alkaloids
–
Examples

Vincristine and Vinblastine (Bladder, breast, HL, NHL)
– MOA: Prevent disassembly of microtubules-Stops mitosis
– ADR’s : Neuropathy

Paclitaxel (Taxol®) and Docetaxel (Taxotere®) (Ovarian
and breast CA, Non-small cell lung CA)
–
–
MOA: Prevent formation of microtubules-Stops mitosis
ADR’s: Neuropathy, Alopecia, Bone marrow suppression
Chemo examples cont.

Topoisomerase Inhibitors
–
MOA


–
Examples

–
Etoposide (AML, lung, NHL)/Teniposide (ALL, NHL)
ADR’s

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Prevent repair to DNA
Defragments the DNA
Leukopenia
Anthracyclines
–
MOA

–
Examples

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Produce free radicals--->cytotoxicity
Doxorubicin (Adriamycin)-Bladder, Breast, HL, NHL, others
Daunorubicin-ALL. AML
Doxorubicin liposomal (Doxil®)-Encapsulated doxorubicin-Ovarian CA, sarcomas
Mitoxantrone is similar, and less cardiotoxic-AML, Breast, NHL
ADR’s


Leukemia, Myelosuppression, GI toxicity, vesicants
Cardiotoxic at doses of 500-550mg/m2
Chemo examples cont.
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Alkyalators
–
MOA

–
Examples
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Breaks DNA strands by adding alkly group
Cyclophosphamide (Cystitis)-Bladder, Breast, CML, lung, NHL
Ifosfamide (Less myelo, more cytotoxic)-Breast, NHL
Melphalan (Leukemia, pulmonary fibrosis)-Breast, multiple myeloma, ovarian
Busulfan (Pneumonitis)-CML
Nitrosureas such as BCNU and CCNU (Myelosuppression, pulmonary fibrosis)-HL, NHL
Platinums such as Cisplatin and carboplatin (Cause DNA cross linking)-Bladder,
esophagus, ovarian
ADR’s

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Mutagenic--->Leukemia possible
Myelosuppression
Emetogenic
Nephro and Neurotoxic (Platinums)
Chemo examples cont.

Antibiotics
–
MOA
 Breaks
–
DNA and generates free radicals
Examples
 Bleomycin
(HL, NHL, testicular)
 Mitomycin C (Breast, colorectal)
–
ADR’s
 Pulmonary
toxicity if > 200U/m2 (Bleomycin)
Targeted therapies

Cell surface antibodies
–
Rituximab (Rituxan®) (anti CD 20)

–
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Chimeric (Mouse + Human antibody)
Cetuximab (Erbitux®) (anti C 225)
Trastuzumab (Herceptin®) (anti Her 2 Neu)
Bevacizumab (Avastin®) (anti VEGF)
Small molecules
–
–
Gefitinib (Iressa®) (anti EGFR)
Imatinib (Gleevac®) (anti bcl oncogene)
Chemotherapy
There are MANY others
 Do not try to memorize

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Have listed for completion
Understand CONCEPTS
List continues to evolve
–
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New medications
New uses/indications
Chemotherapy Complications

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This I will test on (generalities)
Myelosuppression-Most Common Dose Limiting Toxicity
– Usually seen 10-14 days after dose
– Usually recover 21-28 days
– Neutropenia---> Fever (Covered later)
– Low platelets usually a problem is <20K.
Alopecia
– Cyclophosphamide, Dactinomycin, Doxorubicin
– Paclitaxel, Vincristine
Chemotherapy Complications

Nausea and vomiting (Emetogenic)
–
–
Some drugs affect vomiting center,
chemoreceptor trigger zone
Pretreatment helps
Chemotherapy Complications-II

Nausea treatments
–
–
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Prochlorperazine (Compazine®), Chlorpromazine
(Thorazine®) (Anti-dopaminergic)
Metoclopramide (Reglan®) (Anti-dopaminergic)
Ondansetron (Zofran®), Ganisetron (Kytril®), and
Dolasetron (Anzemet®)

–
–
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Selective 5HT receptor antagonists-Block serotonin
Dronabinol (Marinol®)-THC
Glucocorticoids
Benzodiazepines
Chemotherapy Complications-III

Stomatitis
–
–
Most chemo can cause
Topical anesthetics (Lidocaine viscous)
Hormonal treatment of cancer-I

AdrenocorticosteroidsLeukemia/Lymphoma
–

May help programmed cell death
Antiandrogens
–
i.e.: Flutamide (Prostate CA)
Hormonal treatment of cancer-II

Estrogens
–
–

Prostate CA historically
Breast palliation (DES, ethinyl estradiol)
Antiestrogens
–
Tamoxifen (Breast CA)
Tamoxifen

Use in breast CA
–
–
–

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Treatment
Prevention
Reduces occurrence and reoccurrence in women with
breast cancer or high risk for breast cancer
Binds estrogen--->Agonist/antagonist
Advantages: Decreased cardiovascular disease
and osteoporosis
Disadvantages: Menopause, thromboembolism,
Endometrial CA
Hormonal treatment of cancer-II

Progestins
–
–
–

Endometrial and breast CA
i.e.: Medroxyprogesterone, megestrol acetate
Disadvantage: Irregular menses and weight
gain (Megace® 800mg per day of suspension
used to treat poor appetite/Cancer cachexia)
Aromatase inhibitors
–
–
–
Aminoglutethimide-Prostate cancer
Letrozole (Femara®)-Breast cancer
Decrease steroid synthesis
Hormonal treatment of cancer-III

Gonadotropin-Releasing Hormone agonists
–

Leuprolide (Lupron®) decreases androgen
levels (Prostate CA)
Somatostatin analogues
–
Octreotide (Sandostatin®) (Carcinoid,
vasoactive intestinal peptides secreting tumors)
Other treatments for Cancer
Bone Marrow Transplantation
Kill one’s own cells
 Replace with own cells treated
(Autologous)
 Peripheral stem cell transplant
 Or, replace with another’s cells
(Allogeneic)
 Best use: Acute leukemia, Hodgkin’s, NonHodgkin’s, Testicular

Immunotherapy

Monoclonal antibodies
–
–
Were investigational for treatment
Now proven
 IE:
–

Mouse antibodies… Rituximab)
Used in diagnosis (PSA, CA 125)
Cytokines-Next slide
Immunotherapy-Cytokines

Interferon
–
–

Use: CML, Hairy Cell leukemia, Kaposi’s,
Melanoma
Flu like side effects
Interleukins
–
–
Stimulate T cells and Natural Killer cells
IL-2 (Renal cell, melanoma)
Growth factors (GF)
Colony stimulating factors that are IL like
 Neutrophils

–
Granulocyte-Macrophage Colony Stimulating
factor (G-CSF)
 Granulocytes,
monocytes, eosinophils
 Filgrastim (Neupogen®), Pegfiltrastim (Neulasta®)
Growth factors (GF)-Cont.

Red cells
–

Erythropoietin (Epoetin alfa (Epogen®,
Procrit®), Darbepoetin alfa (Aranesp®)
Platelets
–
Thrombopoietin (TPO)
Vaccines
Usual vaccines should be given, perhaps
prior to treatment
 Adults

–
–
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Tetanus
Influenza
Pneumococcus (particularly if splenectomy
planned)
Other treatments-Research
Cellular therapy-Grown cells implanted into
CA patient
 Vaccines

Other treatments
Nutritional
 Supplements
 Largely unproven
 Aspirin may reduce cancer 2010???

Genetic screening

Should just mention here….
A budding field
 Experts are available regionally (bigger
centers)

Some specific cancers worth
mentioning
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Skin
Lung
Breast
GI
–
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Others
Colorectal
Myelodysplasia
Lymphoma
Leukemia
I will not test you on which chemo works for which tumors
Skin Cancer


Melanoma
Non-Melanoma
–
–
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Sun exposure major RF
–
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–

70-80% Basal cell
20% Squamous cell
Equator worse
Light skin worse
Face including ears and nose
Less risk in dark skinned individuals
Basal cell skin CA (BCC)
Arises from the basal cells of skin
 Slow growing typically
 Pearly nodule
 Telangectasias
 Treatment-next slide

BCC Treatment

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Cut out
Electrodessication and curettage
Cryosurgery if low risk
RT
Laser
Moh’s
–
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–
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Specialized form of dermatology/pathology
Anesthesia, remove lesion to edge
Frozen section, stain for pathology
If residual tumor (edges not free of disease) more surgery
After borders clear, done!
Allows smaller excision/Better cosmesis
BCC prevention/treatment

Fluorouracil
–
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–

Treats actinic keratosis
Reduces progression to skin cancer
5 fluorouracil (5FU) (Efudex®)
Immunomodulators
–
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Similar indications as flourouracil
Imiquimod (Aldara ®)
Squamous cell skin CA (SCC)
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From keratinizing epidermal cells
Malignant-Can metastasize
Ulcerated erythematous nodule
Actinic keratosis precursor
–
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Hyperkeratotic papule
Wider excision ?
RT
Mets: LN resection, RT or both
13-cis-retinoic acid (1mg po qd) + Interferon α (3M units
sc or IM qd)
Melanoma

From neural crest derived melanocytes
–

May be amelanotic
4 types
–
Superficial

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Superficial spreading
Lentigo maligna-chronic sun exposure
Acral lentiginous-palms, soles, nails, mucous membranes
Deep

Nodular-typically heavily pigmented and deep invasion seen at
time of dx
Melanoma-Prognostication
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Breslow’s thickness (worse if more than 1mm
depth at time of dx)
Ulceration
Node involvement
Satellites
Mets
Clark’s staging
–
Ranges from early in situ disease (I) to penetrating fat
(V)
Melanoma eval and TX
Spreads via lymph nodes and blood
 Biopsy
 Wide excision

–
2-4cm typically
LN bx
 IFN α, dicarbazine (DTIC), nitrosureas like
BCNU, cisplatin/carboplatin, vincristine

Lung Cancer

Tumors derived from respiratory epithelium
–
88% are

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Small cell (oat cell)-central tumor
Squamous-central tumor
Adenocarcinoma-peripheral tumor
Large cell-peripheral tumor
“LA is on the coast”
Others include



Mesotheliomas
Lymphomas
Sarcomas
Lung cancer-II
Really two types based on course
 Small cell (SCLC) and non-small cell
(NSCLC)

–
–
Small cell tends to spread early
Non-small cell has option for surgical cure,
early in disease
Lung cancer III
90% are tobacco users
–
–
–
–
–
Lung cancer is largely a disease of smokers (Peter
Jennings)
Don’t let media fool you (Christopher Reeves’ wife)
Recent data suggests more non-smoking women are
getting cancer than non-smoking men
Second hand smoke?
Radon?
Lung CA-Overview

Symptoms (about 5 of 6 pts)
–
–
–
–
–
–
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Cough
Hemoptysis
Weight loss
Dyspnea
Post obstructive pneumonia
Chest pain
Paraneoplastic syndrome
Lung cancer radiography

Incidental chest x-ray
–
–

About 1 in 6 lung cancer patients are
asymptomatic
While often found this way, screening CXR’s
in smokers do NOT improve survival in those
screened (no reduction in death rates)
Chest CT scan
–
May be better at screening (recent studies), but
who will pay?
Solitary pulmonary nodule



X-Ray density 1-6cm in size
35% are malignant, most being lung CA
Can be followed serially in low risk pts
–
–
–

Old x-rays
Q3mo CT for one year then annual until stable
No change in character in 2 years or favorable
appearance (i.e.: dense calcium center) suggest benign
Biopsy should be considered in higher risk
–
–
Older than 35
Tobacco history
Lung CA work up
CXR
 CT
 Positron emission tomography (PET)
 Look for paraneoplastic syndromes (later
lecture)

–
–
Common in lung malignancies
Systemic disease?
Lung CA diagnosis

Fluid
–
–
–

Aspiration of pleural effusion
Sputum cytology
Bronchoscopy
Biopsy
–
–
–
Needle (CT guided? Interventional radiologists, chest
surgeons)
Open lung (thorocotomy)
LN
Small cell lung CA (SCLC)

Two types-That’s it!
–
Limited stage (30% pts)



–
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Extensive stage
Note early mets to brain 10% pts

–
–
Single sided
Regional lymph nodes only
“One radiation therapy port”
Prophylactic RT does NOT improve survival
Also bone marrow mets in 20-30 % pts
Bone scan
SCLC-Chemo
Median survival 6-17 weeks without TX
 40-70% respond to chemo

–
Response predicts increased survival
Etopiside + cisplatin/carboplatin
 Others active include paclitaxel, irinotecan,
others

Non-small cell lung CA (NSCLC)

TNM staging
NSCLC Treatment approach
1/3 of pts are candidates for surgery at
diagnosis
 1/3 are in the middle
 1/3 have distant mets

NSCLC-Surgery

Consider if
–
–
Healthy pt
Early stage disease
 IA,
–

IIA, IB, IIB
Local disease
Contraindicated if FEV1 <1L
–
If over 2.5L may be candidate for
pneumonectomy
NSCLC-Chemo
20-30% response rate
 9-10mo median survival
 1 year survival is 40%
 Paclitaxel + Carboplatin/Cisplatin
 Vinorelbine + Cisplatin
 Others active include docetaxel, irinotecan,
gemcitabine, Gefitinib (Iressa®)

Breast Cancer diagnosis

Breast exam
–
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–
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
Axilla (Apex of axilla, slide fingers down across chest
wall)
Skin (distortion? Edema?)
Breast itself (Attention upper outer quadrant….most
CA there! Firm, painless, non-mobile mass)
Nipple (discharge?)
Self breast exam does NOT decrease death rates (large
Chinese study c 2001) but is easy and safe
Persistent Masses should be biopsied
Cystic masses may be aspirated
Breast radiography

Mammograms
–
–

Ultrasound
–
–
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Cystic vs..... solid mass
Needle localization
CT scan
–

Begin at 40 and repeat annually
Looking for clustered microcalcifications, spiculated densities,
architectural distortion
No better
MRI
–
–
–
–
New
May be better (cost wise) for higher risk patients
Under extensive study
Not necessarily better
Breast cancer miscellany

Mutated BRCA-1 tumor suppressor gene
–
–

Mutated p53 tumor suppressor gene
–

60% chance of developing breast CA
33% chance of ovarian CA
Seen in 40% of cases
See blurb on HRT risk of breast CA in
handouts
Breast Cancer

Surgery
–
–
–
–
–
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Needle localization vs..... stereotactic bx?
Only 1 in 5 to 1 in 10 who get bx have cancer
Breast conserving tx (lumpectomy plus RT) as good as
mastectomy
LN bx axilla usually done
If tumor <1cm surgery may be enough if LN neg
If >5cm usually need mastectomy
Breast CA-Chemo issues

Usually multi-drug regimen are used either
for metastatic disease or for adjuvant tx
–
–
–

First line doxorubicin + cyclophosphamide
CMF (cyclophosphamide + Methotrexate +
Fluorouracil or many others
Second line Anthracycline or paclitaxel based
treatment
Hormone treatment
Breast Cancer-Hormone treatment

Tamoxifen (Nolvodex®) 10-20 mg po qd
–
–
–

Agonist/Antagonist to estrogen
For 5 years
Usually in post-menopausal woman after
chemo done
Letrozole (Femara®) 2.5 mg po qd
–
–
Now follows tamoxifen for 5+ years
May go right to Letrozole without Tamoxifen
Breast Cancer-Prognosticators

Tumor stage
–
–

Receptor status
–

Size of mass (Larger obviously worse)
LN status (Positive obviously worse)
Estrogen Receptor (ER) and Progesterone Receptor (PR) positivity
suggest better prognosis
Other tumor issues
–
–
–
–
Slower growing tumor better
Histology (poor histological grade, worse)
erbB2 (HER-2/neu) gene (worse)
Mutant p53 gene (worse)
GI Malignancies
Esophagus
 Gastric
 Colon/Rectal
 Liver
 Pancreas
 There are others that will not be covered
here

Esophageal cancer
Largely a disease of smokers coupled with
alcohol overuse
 Role of GERD prominent
 A lethal CA

–
5% 5 year survival
May have dysphagia and wt loss (bad
prognosis)
 Dx: EGD, biopsy

Esophageal CA-Treatment
About 45% of pts are candidates for surgery
 RT often precedes (Neo-Adjuvant)
 Chemo-poor response
 Palliative care?

–
Feeding tube
Gastric cancer



Nitrates (hot dogs, smoked foods) increase risk
Helicobacter pylori association
Ulcers in stomach found must be followed for
resolution
–

May hide gastric CA
Treatment
–
–
–
Chemo-5FU + doxorubicin based
Surgery
RT-not very helpful
Colorectal cancer-Associations

Hereditary issues
–
Familial polyposis syndromes


Autosomal dom
May reduce risks with prostaglandin blockers
–
–

NSAIDS including aspirin, and
COX-2 inhibitors such ask celecoxib (Celebrex®)
Inflammatory bowel disease
–
–
–
After 10 years of diagnosis, 1% increase risk per year
8-30% risk after 25 years of diagnosis
>15 years consider prophylactic colectomy
Colorectal CA-signs and symptoms

Screening
–
–

Stool tests for blood
Colonoscopy
Blood loss
–
–
Hematochezia (blood in stool)
Iron deficiency anemia must be worked up
Abdominal pain
 Obstruction (bad)

Colorectal cancer-Prognostication
Depth of invasion
 LN involvement
 Mets
 Surgically resectable disease likely to do
better

Colorectal cancer treatment
Resection when possible
 RT in the case of rectal cancer

–

Harder to resect disease deep in pelvis
Chemo
–
–
–
5FU is single most effective single agent
Usually combined with leucovorin
Others include Irinotecan (CPT-11)
Liver tumors
Primary (hepatocellular, hepatoma) or
Secondary (metastatic)
 Primary associated with cirrhosis, viral
hepatitis C.

–

Elevated AFP
Metastatic-Must find primary
Pancreatic cancer

Difficult to diagnose and treat
–
–



5 year survival only about 10%
98% fatality
Cause unknown
CA 19-9 excellent tumor marker
May present with vague or specific symptoms
–
–
–
–
Abd pain
Jaundice with itching
Weight loss
Clay colored stools (plugged bile duct, not bile in stool)
Pancreatic Ca-Diagnosis
CT
 Abd U/S

–
Endoscopic ultrasound (EUS)
MRI
 PET scan may help (not that great)
 Endoscopic retrograde
cholangiopanreatography (ERCP)
 Percutaneous bx or by laparotomy

Pancreatic Ca-Treatment

Complete excision is only thing that substantially
impacts survival
–
–
–

Chemo
–
–

Only 10-15% of pts are candidates when found
Surgery has 15% mortality rate
Pancreaticoduodenectomy (Whipple procedure)
5FU + gemcitabine
Others
RT?
Myelodysplasia

Ineffective hematopoesis
–
–

Many classification systems
–
–
–

Dyspoeisis-Abnormal functioning marrow
Results in cytopenias
French American British (FAB)
Modified by World Health Organization
Table 94-5
Requires bone marrow biopsy
–
–
Standard bone marrow prep
?Philadelphia chromosome (CML and ALL)




The first reproducible chromosome abnormality in human malignancy.
9, 22 translocation allows ABL oncogene to be close to BRC (breakpoint cluster region)
Gene product leads to independent cell growth
Gleevec blocks the response to this (A new form of chemo, now available for CML)
Myelodysplasia- Approach to
treatment



Observation?
Support
Drugs may help
–
–
–



Thalidomide
Azacitine (Vidazza®)
Others (Dacagoen, ARA-C, Angiogenesis inhibitors such as
Avastin® (used for colon CA), other growth factors
Transfusion
Bone marrow transplant in younger pts (<65)
Treat aggressively if conversion to leukemia
Lymphoma

Hodgkin’s vs...... non-Hodgkin’s
–
–
Reed Sternberg cell (large cell with bilobed nucleus…owl’s eye
appearance) is key microscopic feature in Hodgkin’s lymphoma
90% survive Hodgkin’s



B symptoms
–
–
–


RT responsive
Doxorubicin+bleomycin+vinblastine+acarbazine (ABVD)
Fever
Night sweats
Weight loss
Often incurable
T cell lymphomas have HTLV-1 retrovirus association
NH lymphomas



Classified broadly into aggressive and indolent
Includes low grade small cell lymphomas, mantle
cell lymphomas arising from the mantle zone of
the follicle, and mucosal associated lymphoma
(MALT) associated with H. pylori
6 classification systems exist
–
Ann Arbor most common


LN status
Presence of B symptoms
NH Lymphoma treatment

Aggressive
–
–
Goad of cure
Multiple meds (many combos) or BM transplant




Most common is CHOP
(Cytoxan+adriamycin+vincristine+prednisone)
May add Rituxan (Anti CD 20, against a cell surface AB)
RT
Indolent-next slide
NH Lymphoma treatment cont.

Indolent
–
–
–
–
–
Slower growing
Quality of life (watchful waiting?)
Chemo may not alter survival
Treat when symptoms, bulky disease
Drugs include alkylators, vinca alkaloids,
anthracyclines, nucleoside analogues (Fludara),
and targeted therapies (Rituxan)
Leukemias-4 broad categories
Acute
Chronic
Lymphocytic
ALL
CLL
Myeloid
AML
CML
AML


>20% myeloblasts
WBC’s elevated
–

Non-specific s/s
–
–
–

Fatigue, weak
Pain, fever
Enlarged LN’s, or hepatosplenomegaly
Progostics
–

Usually >15K
Old, worse
Treatment-next slide
AML-Treatment

Induction chemotherapy
–

Attempt CR
–

Cytarabine (cytosine
arabinoside)+anthracycline +/- etoposide
Increased survival
Treat relapses
CML

Often have chromosome 9, 22 translocation
–
–
–

s/s
–
–
–

T (9,22)
Seen in 90-95% of pts
MC is Philadelphia chromosome
Usually insidious onset
Hepatosplenomegaly
Elevated WBC with <5% blasts
Treatment
–
–
Cured with allogeneic BM transplant (Family or matched donor
with 5-6 MCH Ag match)
Imatinide (oral chemo that inhibits ATP binding inducing
apoptosis)
ALL
B cell AL is MC CA in children
 May have Philadelphia chromosome

CLL
B cell CLL is MC lymphoid leukemia
 Prolonged survival likely

–

Median survival is 10 years
Treatment
–
–
–
Chlorambucil PO or
Fludarabine IV or
Both
Other cancer topics
Palliative care
Definition
–

Giving relief of the symptoms without curative
intent
Decisions
–
–
Cure or not to cure
Must take into account physical, emotional,
spiritual needs
Palliative Issues


Pain
Cancer complications
–
–

The “C” word
–
–

Bleeding
Obstruction
Fear of cancer
Stigma of having cancer
Fear of dying
–
DNR orders
Hospice
Originally in Europe, a place for weary
travelers in the Middle Ages
 Today, the compassionate care given in
homes or institutions to the terminally ill
 “Dying with dignity”

Hospice-cont.




Effort on the part of many including physicians,
nurses, social workers, counselors, volunteers,
religious, etc.
Helps the dying AND their family
Attention to pain control
Settings
–
–
–
Home
Inpatient setting
Outpatient setting (hospice houses)
Hospice specifics/treatments
Pain control (future slide)
 Nausea

–
–
Prochlorperazine (Compazine®) po or pr,
metochlopramide (Reglan®) po or IV
Newer agents (Zofran®, others po or IV)
Hospice specifics/treatments cont.

Constipation
–
–
–
–

Terminal secretions (“Death rattle”)
–
–

Stool softeners (docusate (Colace®))
Laxatives
Non-absorbable sugars (lactulose)
Newer agents polyethylene glycol (Miralax®)
Atropine injectable or eye drops given po
Scopolamine IV, IM, sc, patch
Seizures in brain mets
Pain medication in palliative care


Short-vs-Long acting?
Route
–
–
–
–
–

IV
IM
SC
Topical (fentanyl (Duragesic®))
Intrathecal (pump)
Constipation may be limiting, particularly if
dehydrated (New med for this c 2008 Relistor®
(methylnaltrexone bromide))
Communicating Bad News
Difficult
 Requires tact and experience
 Do you tell the patient? The family? Sugar
coat it?
 Will pt lose hope and perhaps give up?
 Should you stop usual meds (i.e.: cardiac
meds)?

Case
Evaluation
 Diagnosis
 Staging
 Biopsy
 Treatment/planning
 Follow up

Summary






Treatment of cancer requires understanding of
stage of disease
Stage and knowledge of best treatment is key
Combination of surgery, radiation, and
chemotherapy, hormones, supportive care may be
used
Anticipate complications of treatment
When you can’t cure, keep comfortable
Cancer is a scary diagnosis, but with team
approach, can be treated successfully
Where to get more information
Harrison’s or Cecil’s
 DaVida’s textbook of oncology
 American Cancer Society-Excellent
reference, including on line resources
