Oncology

• A distant effect of malignancy mediated by factord secreted by, or tirggered by, the malignancy
• May develop before or during the malignancy
• May parallel the course of the disease

• Symptoms
• Fatigue
• Anorexia, abdominal pain, constipation
• Polyuria, polydipsia
• Mental status changes
• Sudden death

• Objective findings
• Renal dysfunction
• Shortened QT interval, PR prolongation, bradycardia
• Hyporeflexia

< 6 months

• Used primarily in multiple myeloma, where the tumor is responsive
• Also useful in lymphoma and occasionally in breast cancer
• Blocks production of the "activating factors"
• May also increase calcium excretion in the urine

• Inhbits bone reabsorption by reducing the number and activity of osteoclasts
• A vweicant, and must be given IV
• Ca level should decrease within the first 48 hours
• May require retreatment in 72-96 hours
• Side effects include thrombocytopenia, liver toxicity, and coagulopathy

• Inhibits bone reabsortion by binding to osteoclasts
• Works very quickly, within hours, to decrease calcium with peak action at 48 hours
• May develop tachyphylaxis, so cannot use it more than once or twice
• More effective with the addition of steroids

• Mainstay of therapy for hypercalcemia
• Concentrated in areas of high bony turnover
• Take up by the osteoclasts and inhibit their action
• May have effects on the osteoblasts also
• Pamidronate has proven efficacy in all types of hypercalcemia with decreased skeletal events in both breast cancer and multiple myeloma
• Zoledronic acid also approved for malignant hypercalcemia
• Toxicity is primarily renal insufficiency

• Primarily caused by small cell lung ca
• Associated with medications such as cyclophosphamide (Cytoxan or Neosar)
• Arised secondary to production of ectopic ADH, which acts in the kidneys to cause retention of free water
• Results in hyponatremia in the setting of less-than-maximally dilute urine and a normal volume status
• May be severe with symptoms of mental status changes, nausea, anorexia, and weakness
• When extreme, may result in coma, seizures, and death

• Fluid restriction -- works best i mild cases with restricition to 500 ml to 1 L per day
• IV saline plus lasix
• Conivaptan for acute treatment
• Demeclocycline for chronic treatment
• Treat the underlying malignancy

• Occurs frequently in small cell carcinoma, carcinoid tumors, and inassociation with MEN 1 syndrome
• Ectopic ACTH production
• Initiates excessive production of glucocorticoids and mineralocorticoids by the adrenal glands
• Presentation is commonly seen with hypokalemic alkalosis
• Also see weakness, hypertension, and hyperglycemia
• If develops slowly, will see the syndrome with a buffalo hump, moon facies, hyperpigmentation, and hirsutism

• Diagnosis is made by finding:
• Elevated ACTH levels
• Elevated cortisol levels that typically do not suppress with dexamethasone

• Treatment options include:
• Treatment of the primary tumor
• Inhibitors of steroid synthesis, such as ketoconazole or an aminoglutethimide

• Commonly associated with visceral adenocarcinomas such as stomach, breast, lung, and ovary
• Should consider malignancy in the older pt with dermatomyositis
• Polymyositis associated with skin changes
• -Proximal painless muscle weakness
• -Violaceous rash on eposed parts, especially the eyelids
• -Dysphagia is common
• -May develop weakness of he respiratory muscles

• Diagnosis is made by finding:
• -Elevated CPK, aldolase, LDH, and ESR
• -Abnormal EMG
• -Muscle biopsy with necrosis of muscle fibers and an inflammatory reaction

• Treatments include:
• -Steroids
• -treatment of the underlying malignancy

• "Clubbing"
• Commonly associated with lung cancers, although may be seen with CF, chronic pulmonary infections, or IBD
• May range from clubbing to severe periostitis and arthritis
• Cause is unknown

• Treatment:
• -Salicylates/NSAIDs
• -Steroids
• -Effective tumor therapy

• Occurs primarily in small cell lung cacer
• Variant of myasthenia gravis
• Initial symptom: weakness of the proximal muscles
• Autoimmune in nature, secondary to autoantibodies that resut in impaired release of acetylcholine
• Diagnosis: is made by finding an abnormal EMG with improvement in strength upon repetitive stimulation
• EMG is usually unaffected by addition of edrophonium chloride

• Treatment includes:
• -Treatment of malignancy
• -Guanidine
• -Plasma exchange
• -IVIG
• -Immunosuppression - Imuran, steroids, cytoxan

Thoracic > Lumbosacral > Cervical

• MRI
• Need tissue diagnosis to decide best treatment

• Radiation therapy is themainstay of therapy
• Steroids are usually given concomitantly to reduce edema
• Laminectomy is used for patient who need a tissue diagnosis or are unable to have radiation therapy
• Chemotherapy is usally combined with radiation for those sensitive tumors

• Immediate large doses of steroids (usually IV dexamethasone)
• If the lesion is single, resection or stereotactic treatment may be tried
• For multiple lesions, and after any resection, whole brain radiation therapy should be given

• Diagnosis is by pleural fluid cytology -- exudative
• May require multiple samples and large volume for diagnosis
• Occasionally may need pleural biopsy or thoracoscopy for diagnosis

• Therapy directed to the primary tumor
• Symptomatic management with thoracentesis
• If recurrent, then pleurodesis with Talc, Doxycycline, or Bleomycin

Lung

• ACS recommends CBE yearly after 40
• USPSTF concludes that evidence is insufficient to recommend for or agains routine CBE

• ACS recommends MMG done yearl after age 40 (supported by AMA and ACR)
• USPSTF recommends screening with or without CBE every 1-2 years after age 40
• Controversy surrounds age to stop MMG. Should be done after 70 in healthy women
• Some data support idea that is is not cost-effective after age 79

• Start from age 40 yearly all the way to age 70 and probably all the way through as long as the pt is healthy
• Breast self exam should be done yearly after 40

• Age is the most significant risk factor.
• Risk rises to 1 in 8 by age of 85
• Involvement of 1st degree relatives with early or bilateraly breast cancer increaseas the risk substantially
• Genes -- BRCA1 and BRCA2
• Benign breast disease increases your risk of subsequent breast cancer
• -Atypical ductal hyperplasia
• -DCIS
• -LCIS
• Previous breast cancer also increases the risk of a second breast cancer

• Found in Chromosome 17
• Autosomal dominant
• Lifetime risk if developing breast cancer is 50-85%
• Also increases the lifetime risk of developing ovarian cancer to 33%
• Associated with an increase in the risk of breast and prostate cancer in men

• Chromosome 13
• Autosomal dominant
• Similar risk for breast cancer as BRCA1 (50-85%)
• Somewhat smaler risk for ovarian cancer (10-20%)
• Associated with increased incidence of breast cancer in men

• painless breast mass detected by the patient
• Occasionally may present as eczema
• May complain of a nipple discharge
• May develop nipple retraction or dimpling of the skin

• Solid vs. cystic
• -Can determine using US
• -If cystic, aspirate; if bloody fluid or recurs, then should biopsy
• -If solid, FNA or core biopsy

• Palpable mass without abnormality on mammogram
• -- biopsy

• -Should send tissue for hormone receptors -- specifically estrogen and progesterone
• -Should send tissue for HER2/neu assay

Prior to further intervention, will need to survey for distant metastasis

• Tumor size
• - Greater than 2 cm denotes a worse prognosis

• Number of involved axillary nodes
• -most important prognostic factor
• -prognosis worsens with each positive node
• -can use sentinel node dissection to assay

• Other prognostic factors:
• -Hormone receptor status -- if ER/PR receptor-negative, then expect a higher incidence of recurrence
• -HER2/neu status -- overexpressionof HER2/neu denotes a more aggressive tumor

• 1. Modified radical mastectomy
• 2. Breast-conserving surgery
• -Lumpectomy with axillary node dissection
• -Should always be paired with local radiation therapy to decrease the local recurrence rate
• -give equivalent results to mastectomy

• Tumor < 1 cm with negative nodes -- no treatment is indicated
• Any-sized tumor with positive nodes -- needs further treatment with either adujuvant chemo OR hormonal therapy OR both
• All patients with positive hormone receptors should receive hormonal therapy for 5 years
• If HER2/neu positive, add tastuzumab

• < 1 cm tumor, node-negative, ER/PR+/- ==> no further treatment
• Any size tumor, node-positive, ER/PR+ ==> chemo followed by hormone therapy (tamoxifen)
• Any size tumor, node positive, ER/PR- ==> chemo
• Trastuzumab if HER2/Neu+ and node-positive

• < 1 cm tumor, node-negative, ER/PR+/- ==> no further treatment
• Any tumor size, node-positive, ER/PR+ ==> hormone therapy (aromatase inhibitors) +/- chemo
• Any tumor size, node-positive, ER/PR- ==> chemo
• Trastuzumab if HER2/neu+ and node positive

• With metastatic disease: if hormone receptor-positve, may use hormonal therapy alone unless there is evidence for visceral mets
• If hormone receptor-negative or has visceral mets, then use combination chemo
• Bisphosphonate therapy for bony disease

• Benighn
• Mote common than lobular
• See microcalcifications on mammogram
• High-grade has higher risk of evolving into invasive disease
• Treatment is mastectomy vs. breast conservation surgery +/- XRT followed by tamoxifen

• Nonpalpable with no reliable mammographic changes
• Marker for cancer development in either breast
• Frequently is multifocal and bilateral
• Treament varies from observation only to tamoxifen to bilateral mastectomy

• The use of tamoxifen therapy has been demostrated to reduce the risk of developing breast cancer in patients with increased risk
• Should be used in those women felt to be at high fisk for breast cancer development such as those with:
• -Previous cancer
• -Strong family history
• -BRCA1 or -2- positive
• Aromatse inhibitors also now proven for prevention

• Increased risk of endometrial cancer
• Risk of thrombosis
• DVT/PE
• Cataract formation

• osteoporosis -- need to screen for this and prevent
• arthralgias
• no thrombosis or malignancy risk

• The third most common female genital tract cancer after uterine and ovarian
• Mortality has dropped significantly with the introduction of effective screening
• Peak age is 20-30 with a later peak in the 60s
• Usually slow, progressive disease

• a sexually transmitted disease
• Associated with:
• -Early age at first intercourse
• -Multiple sexual partners
• -Low socioeconomic status
• HIV
• Primary risk factor is HPV, especially types 16, 18
• Testing for HPV not a good screening tool, because up to 30% of women with normal pap smears have infection

• Recombinant vaccine
• Recommended for ages 9-26
• Best if given before sexually active
• Ages 11-12
• Covers POV types 6, 11, 16, and 18
• -6 and 11 estimated to cause 90% of genital warts
• -16 and 18 cause 70% of cervical cancer

• Pap smear screenig for all women over the age of 21 or within 3 years of becoming sexually active
• Annually until age 30
• After age 30, if 3 negatives obtained, ay screen every 2-3 years unless risk factors present
• After age 30, may combine pap and HPV DNA test and, if both negative, repeat every 3 years
• May stop at physician's discretion or at 70 with 3 normals and none abnormal in last 10 years

• Requires biopsy to further define the diagnosis
• ASCUS diagnosis -- repeat in 3-6 months and if still abnormal, need colposcopy. If glandular, go directly to colposcopy

• Typically, LGSIL and HGSIL will require further evaluation with colposcopy and biopsy
• --LGSIL occasionally (15%) progresses to invasive cancer
• --HGSIL is more likely to be higher-grade dysplasia with increased risk of malignancy

• CIN I -- observation vs. cryotherapy
• CIN II and III -- ablation or excision
• After definitive therapy, mus follow with frequent pap smears (3-4 mos, the every 6 months)

• Staging is by the FIGO guidelines
• Spreads primarily by direct extension
• Not TNM staging
• Clinically staged with
• -Physical exam CXR
• -IVP if CT scan not done
• -CT scan/MRI

• Influenced by tumor size, nodal involvement, and depth of tumor invasion
• Early-stage disease may be treated with surgical resection only
• More advanced local disease is treated with radical surgery or radiotherapy
• Bulky disease or disease that has invaded the paratetria or nodes is treated with combination chemoradiotherapy

• Close f/u is necessary, because most recurrences occur within the first 2 years
• Pelvie recurrence may be treated with exenteration (exenteration = everything is take out of the pelvic)

• 5th cause of cancer death
• Peak in 8th decade
• Rare before 40

• Incessant ovulation
• --nulliparity
• --low parity
• --infertility
• --obesity
• Family history
• -- most significant risk factor
• --Breast-ovarian syndrome with BRCA1 and BRCA2
• --Lynch II syndrome

• Oral contraceptive use
• Breastfeeding
• Early menopause
• Multiple pregnancies (10% decrease in risk with each)

There is no good screening test

• CA-125
• -not a sensitive tool, but elevated in at least 80% of pts with ovarian ca.
• -May be elevated in multiple tumor types and non-malignant states.

Recommended screening at this time is restricted to those with an increased risk (such as known BRCA1 or 2) and combines pelvic exam, transvaginal U/S, CA-125.

• Typically in younger patients
• Have malignant features but are not invasive
• Diagnosed at early stage
• Long-term survival ov > 90%
• Managed primarily with surgery

• CA-125 level
• CXR
• Abdominal CT scan
• Abdominal US
• +/- UGI series and barium enema
• Staging is primarily accomplished via surgical exploration -- this should include debulking, lymph node sampling

• Primary surgical resection
• --the amount of remaining disease has a direct correlation to long-term survival
• Chemotherapy
• --Combination of paclitaxel and cisplatin are standard of care
• Radiation therapy -- not often used

• Stage I with no residual tumor is treated with surgical resection only
• Chemo is added if poorly differentiated tumor

Later stage disease with or withour residual disease after laparotomy primarily treated with chemo

• Fewer than 5%
• usually large tumors
• May secrete aFP or BHCG
• Presents with early-stage disease
• Treated with surgery, followed by chemo with agents such as BEP (bleomycin, etoposide, and cisplatin)

• Uncommon tumor but most common in men age 15-35
• Incidence is slowly rising,with seminoma increasing in the HIV population
• Occurs mos often in Caucasian men
• In men over 50, consider a testicular mass to be a lymphoma until proven otherwise

Start workup for lymphoma. This is lymphoma until proven otherwise

• Cryptorchidism
• Prior testicular cancer
• Family history of testicular cancer
• Testicualr feminization syndromes
• Klinefilter syndrome with mediastinal germ cell

• 90% present in the testicles, 10% are extragonadal
• Presentation is most commonly described as a painless mass
• May have pain or swelling suggestive of orchitis
• Back pain ay occur with spine metastasis
• Cough, SOB, and dyspnea with pulmonary metastasis

• Often an inital trial of antibiotics is given if epididymitis or orchitis is suspected
• Testicular US is indicated for a painless mass or painful one that does not resolve ater antibiotics
• US can distingiush between a solid mass and inflammatory changes
• Markers includeing BHCG, AFP, and LDH
• If a mass identified, then an inguinal orchiectomy is indicated for diagnosis
• Remember: the blood supply and lympatics all originate in the abdomen
• A transcrotal approach is contraindicated, because it may introduce tumor cells to different drainage pathways

• Most testicular cancers are Germ Cell Tumors
• --seminoma vs. nonseminoma
• -----nonseminoma --> embryonal yolk sac vs. teratoma/choriocarcinoma

• usually present in the 4th decade
• absence of any other cell type
• If any other elements are present, it is classified as a nonseminoma
• May have some cell of trophoblastic origin and produce BHCG
• They never produce AFP
• Usually localized
• Rarely metastasize
• Very radiosensitive

• Typically present in the 3rd decade
• May be composed of any one of the four histological cell types-- or more than one (mixed germ cell tumors)
• Higher likelihood of metastatic disease at presentation
• 1/3 confined to the testis; 1/3 metastatic

• Tumor markers include:
• AFP -- half-life of 5-7 days
• HCG -- has half-life of 24-38 hours
• LDH

These markers should be checked pre- and post-surgery, and are valuable to predict response to therapy and relapse

• Staging follows the TNM system or the system devised by the IGCCCG
• Staging requireds:
• -Surgical removal of the tumor
• Evaluation of the tumor markers
• CT scan of the abdomen

• Stage I ---> confined to the scrotum
• Stage II ---> retroperitoneal disease
• Stage IV --> distant mets

• Orchiectomy
• Radiation therapy
• Combination chemo
• --most common is BEP (bleomycin, etoposide, and cisplatin)
• --also use EP
• High-dose chemo with BMT support
• Any remaining mass after completion of chemo should be resected
• --in nonseminomas, find: Necrosis/fibrosis, viable tumor, teratoma
• If you find viable tumor, should proceed with 2 additional cycles of chemo

• Infertility
• Second primary germ cell tumor
• Secondary AML
• Secondary GI malignancies

• Nonseminoma of the retroperitoneum is similar to those of testicular origin
• Primary mediastinal has a poor prognosis
• Mediastinal disease is associated with i(12p)
• Mediastinal disease is associated with AML(M7) and with MDS or ET

• A disease of aging men, cancer of the prostate increases after the age of 50
• More than 70% of men over the age of 80 will have malignant cells in their prostate
• 8:1 incidence to death ratio

• Risk factors:
• Age
• Family history of prostate ca
• Increased intake of animal fat
• African-Americans are more affected
• Prostatic hypertrophy is not associated with an increase risk of developing invasive cancer
• Cigarette smoking is not linked
• Previous vasectomy is controversial

• Relatively specific to prostate tissue
• Normal levels increase with age
• May be elevated in other settings
• --Prostatitis
• --Prostate hypertrophy
• --After prostate biopsy
• Not a very sensitive or specific marker
• Elevated in 65% of patients with prostate cancer
• Combination with DRE increases the utility of the marker
• May be more sensitive with use of the age-specific PSA or the percentage of free PSA

Screening recommendation from the ACS: Offer a PSA and DRE annually after the age of 50 to men with a life expectancy of at least 10 years. Also offer to younger men at increased risk of developing prostate cancer

levels over 4 ng/ml

• The diagnostic procedure of choice is a TRUS (transrectal ultrasound) - guided biopsy of the prostate gland
• Typically, 6 biopsies are done encompassing the peripheral zones of the gland
• Remember that BPH usually involves the transition zone, while cancer involves the periphery
• Pathology is almost always adenocarcinoma
• Gleason's histological grade is the most important prognostic feature for prostate cancer
• Gives a grade to both the predominant and secondary growth pattern, and adds the scores
• Total will be 2-10, with higher grade correlated with higher incidence of spread and mortality
• 7 or > Gleason's score is high risk disease

• Treatment at tis stage is designed to palliate symptoms and preserve quality of life.
• Frontline therapy is generally hormonal manipulation
• Remember that the prostate is androgen-dependent, and most cancers maintain some degree of sensitivity to androgens
• Hormonal manipulation may be accomplished by using:
• --anti-androgens
• --LHRH agonists
• --Orchiectomy
• Progression treated with withdrawal or second-line hormonal therapy
• All are palliative

• ETOH and Tobacco abusers
• Woodworkers and textile workers
• Previous head and neck cancer
• A viral association is also noted
• --EBV
• --HPV 16 and 18

• Early stage disease is treated either with surgical resection or radiation therapy
• More advanced disease is treated with combination therapy, with surgery followed by radiation therapy
• Neoadjuvant chemoradiotherapy may be of benefit for preservation of function, particularly in laryngeal cancer

• Clinical syndrome
• Flushing
• Abdominal cramping
• Diarrhea
• Palpitations
• Wheezing

• Effects on the heart
• Valvular heart disease may occur
• Associated findings include:
• --Endocardial fibrosis
• --Often affects the pulmonary and tricuspid valves

diagnosis requires measurement of 24-hour urinary secretion of 5-HIAA (a breakdown product of serotonin)

• With metastatic spread to the liver or the lung, carcinoid syndrome is seen
• Curative treatment is not available at ths stage
• Must treat the symptoms with antidiarrheal meds, Methylsergide, cyproheptadine
• Most effectively treated with somatostatin analogue --ocreotide (can give as a monthly injection)
• Use of chemo is limited

• CT scans, including chest and abdomen
• Bone scan
• PET scan
• +/- mediastinoscopy

• Stage (TNM)
• Performance status
• Absence of weight loss
• Female (they do better)

Age and cell type not an important factor

• Resection of disease if possible, consider adjuvant treatment
• If unresectable (higher stage), consider chemo + radiation
• Metastatic disease -- chemotherapy

small cell and squamous

Adenocarcinoma and large cell

bronchoalveolar

Large cell

Squamous cell

• SIADH
• Cushing syndrome
• Eaton-Lambert syndrome

Hypertrophic pulmonary osteoarthropathy

• Unusual cancer
• Affects men more often
• Linked to smoking
• More common in patients with acquired renal cystic disease
• Common in pts with von Hippel-Lindau disease

• Flank pain
• Hematuria
• Abdominal mass

• Erythrocytosis
• HTN
• Hypercalcemia
• Amyloidosis

• Diagnosis is usually by an imaging technique
• --CT scan
• --MRI
• --US
• Pathology is typically clear cell carcinoma

• Therapy is successful only if the tumor is confined to the kidney and is capable of being resected
• Radical nephrectomy vs. partial nephrectomy
• Solitary metastases may be resected
• May resect venous involvement
• For metastatic disease, treatment is disappointing
• Chemo is not very effective
• Immunotherapy has the most success, with a-Interferon and Interleukin-2 used
• New targeted drugs --VEGF and PDGF tyrosine kinase inhibitors

• Men and women, age 50+ fecal occult blood test (FOBT) annual -or-
• Flexible sigmoidoscopy every 5 years -or-
• Annual FOBT and flex sig every 5 years -or-
• Double contrast BE every 5 years -or-
• Colonoscopy every 5 years

FOBT

Metastatic disease is poorly responsive to chemo and may respond best to immune modulation with a-interferon or IL-2

• Serotonin antagonists (zofran)
• Antihistamines
• Phenothiazine
• Steroids
• Antianxiety agents such as benzodiazepines

• Another side effect of chemo
• Occurs whtn tumor breakdown occurs rapidly
• Release of intracellular contents results in the development of :
• --Hyperuricemia
• --Hyperkalemia
• --Hyperphosphatemia
• --Hypocalcemia

• an oncologic emergency
• The most common cause of chemo-related death
• Fever may result from infection but may also be a manifestation of
• --the tumor itself
• --Medication reactions
• --blood products
• But always assume the cause of fever is infection

• Unique alkylating agent, because it must be activated in the liver
• Breakdown product is acrolein
• Acrolein causes hemorrhagic cystitis
• Prevent with hydration or mesna
• Marrow toxicity and leukemia less likely
• SIADH can occur in high doses

• Many uses -- testicular, ovarian, lung
• Cleared by the kidneys; thus, primary toxicity is renal damage
• May experience magnesium-wasting
• Prevent with hydration
• Also causes peripheral neuropathy and ototoxicity

• Causes more myelosuppression (especially thrombocytopenia)
• Cause less renal toxicity
• Not always interchangeable with cisplatin
• --inferior results in testicular cancer
• --probably equivalent in ovarian cancer

• Drugs that are similar to metabolites in the DNA and RNA synthesis pathways
• Usually compete for a critical enzyme or substitute into the backbone of DNA or RNA, causing disruption
• Maximally effective in cycling cells
• Not associated with profound or prolonged myelosuppression
• Not associated with risk of secondary leukemia
• Examples of commonly used drugs include:
• --5-FU
• --Methotrexate
• --Cytarabine

• Resembles the pyrimidines, uracil, and thymidine
• Incorporates into RNA and disrupts the transcription
• Toxic to the GI epithelium, resulting in significant mucositis and diarrhea
• Enhanced efficacy by the addition of leucovorin

• A folic acid analog
• Blocks the enzyme dihydrofolate reductase
• Blocks DNA synthesis due to the lack of thymidine
• Leucovorin is the "antidote" providing the necessary reduced folate to overcome MTX
• Works best in cells actively cycling
• Must be careful in patients with effusions, because the drug will accumulate in the effusion and slowly leak our, causing prolonged exposure and increased toxicity
• Side effects generally include mucositis and diarrhea
• Used in many tumors such as ALL, head and neck tumors, and breast cancer
• Can penetrate into CNS if used in high doses

• Inhibits the binding of dexycytidine to the DNA polymerase; thus, effectively blocking the production of DNA
• Most active in S phase cells
• In high doses, enters the CNS and may cause cerebellar toxicity
• Used in AML and lymphoma treatment

• Parent compound is camptothecin
• Unique action, with damage occurring by the interruption of the normal nick and repair mechanism performed by the topoisomerase I enzyme
• Cell cycle-specific drug for S phase (like cytarabine)

• Topoisomerase I inhibitor
• Dose-limiting toxicity is neutropenia
• May see nausea, fever, and skin rash
• Used for the treatment of ovarian cancer and lung cancer

• Anthracyclines
• Actinomycin D
• Bleomycin
• Mitomycin C

• Daunorubicin and doxorubicin
• Intercalates DNA and disrupts replication
• May generate DNA breaks by the creation of free radicals
• Active thought the cell cycle
• Must reduce dosage for hepatic toxicity

• Toxicity profile is unique
• Cardiac toxicity occurs with increasing cumulative dosage of the drugs
• Chronic congestive heart failure that is difficult to treat
• Monitor by serial EF assessments and by endomyocardial biopsy
• Reduced by dexrazoxane, which inhibits free readical formation

• Can be given IV, IM, or intracavitary
• Toxicity profile is unusual
• --Fever is common, and occasionally anaphylaxis may be seen
• --Skin reactions include erythema and hyperpigmentation
• --Pulmonary fibrosis is seen with increasing doses or in those having had chest radiation

• Plant derivatives:
• Vincristine
• Vinblastine
• Etoposide
• Taxanes

• From the periwinkle plant
• Binds to tubulin to interrupt the microtubule formation
• Metaphase-specific
• Primary toxicity is neurotoxicity
• Used in ALL, lymphomas

• Almost exactly the same drug as Vincristine
• Mechanism is identical
• Side effect profile is different
• --Primarily myelotoxicity
• --Little neuropathy

• Bind to microtubules, preventing their breakdown into tubulin dimers
• Primarily disrupts mistosis
• Paclitaxel and docetaxel

• Associated with hypersensitivity reactions, which can be prevented by premedication with steroids and histamine blockers
• Causes bradyarrhytmias
• Causes neuropathy, mucositis, and almost universal alopecia that is total body

• Take advantage of tuor-specific properties such as cell surface markers or protein products of the tumor
• Has benefit of little toxicity to normal tissues, unless they express the marker
• May see infusion-related toxicity

• Monoclonal antibody
• Anti-HER2
• Effective in breast cancer that over-expressed HER2
• Binds to a transmembrane receptor in the family of EGFR to block the cascade that drives cell growth had division
• Most effective when combined with chemo, but cardiotoxic when combined with anthracyclines

• Monoclonal antibody
• Anti-CD20
• Effective in CD20-positive lymphomas (B cell)
• Has been modified by the addition of radioactive isotopes to add tumor toxicity
• See infusion-related hypotension, pain syndromes, and hypersensitivities, usually seen in the initial infusion and none in subsequent infusions

CD34

5-7%

• Usually damage to hepatic venues from the prep chemo before the allogeneic bone marrow transplant
• Will see increased bili, weight gain, tender RUQ
• Difficult to treat
• Can be fatal

• a unique toxicity to allogeneic transplant
• Higher risk with unrelated donor source
• May be fatal
• Acute looks like fever, skin rash, GI tract involvement
• Chronic looks like scleroderma

• Prophylactic cranial irradiation reduces central nervous system relapse and improves survival in patients with limited-stage, small cell lung cancer.
• The brain is a frequent site of first relapse in patients after complete therapeutic response. Prophylactic cranial irradiation should therefore be considered for patients with SCLC who have a response to initial chemotherapy.

Men with hypogonadism often have a low prostate-specific antigen level that doubles with therapy and then stabilizes by 6 months after therapy initiation; a greater increase should prompt discontinuation of therapy and evaluation for prostate cancer.

• Patients with a family history of colon cancer or adenoma should undergo a screening protocol at age 40 years or 10 years younger than the earliest diagnosis in the affected relative and with a shortened surveillance interval compared with those at average risk of colorectal cancer.
• The recommended surveillance modality and interval is colonoscopy every 3 to 5 years.

An elevated serum α-fetoprotein level is indicative of a nonseminoma; seminomas are associated with a normal α-fetoprotein level.

Anthracycline therapy with agents such as doxorubicin can cause progressive cardiomyopathy, which can occur acutely during treatment, within weeks to months following treatment, or years after treatment.

Radiation therapy can cause cardiac side effects; the most common manifestations are pericardial disease, coronary artery disease, cardiomyopathy, valvular dysfunction, and conduction abnormalities. Most cases of radiation-induced cardiac disease occur late in the course of the patient’s disease, often 10 years or more following treatment, and occur more frequently with left-sided breast cancers than right, particularly if the internal mammary lymph nodes were not included in the radiation field.

• Platinum-based chemotherapy is the treatment of choice for patients with recurrence of platinum-sensitive ovarian cancer and who relapse more than 6 months after completion of initial therapy.
• Patients who were treated for ovarian cancer with a platinum-based regimen and who maintain a platinum-free interval (the time from the completion of primary platinum-based treatment to the time of recurrence) of more than 6 months are considered to have platinum-sensitive disease.

MRI of the spine

Sunitinib and sorafenib are small-molecule tyrosine kinase inhibitors that improve progression-free survival in patients with metastatic renal cell carcinoma.