approach to the management of adverse effects of.pptx

7/27/2019 Approach to the management of adverse effects of.pptx

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Dr. Mehwesh TajM.B.B.S (Dow),F.C.P.S(Med)Assistant Prof. & Consultant Clinical HaematologistCPSP Approved supervisor Clinical Haematology

N.I.B.D


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Treating cancer with chemical agents

Major role in cancer therapy

Used to cure and increase survival time Some selectivity for killing cancer cells

over normal cells

Normal cells most affected: the skin, hair,

intestinal tissues, spermatocytes, and

blood-forming cells


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Carcinoma Epithelium

Sarcoma Mesenchymaltissue: bone, softtissue

Lymphoma Lymphoid tissueLeukemia Hematopoietic cell


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INCREASED EFFICACY

Different mechanisms of action Compatible side effects

Different mechanisms of resistance

ACTIVITY SAFETY


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Antimetabolites

Antitumor antibodies

Alkylating agentsAntimitotic agents

Topoisomerase inhibitors

Miscellaneous agents

Combination chemotherapy


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Alkylating agents:

busulfan, nitrosoureas, cyclophosphamide,chlorambucil, melphalan, mechlorethamine,

Antimetabolites: methotrexate, 5-fluorouracil, nucleoside

analogues Anthracyclines: doxorubicin, epirubicin


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Antimicrotubule agents: vinca alkaloids, taxanes

Platinum analogues: cisplatin, carboplatin

Topoisomerase II inhibitors: etoposide, tenoposide

Topoisomerase I inhibitors: camptothecins Antibiotics: bleomycin, dactinomycin


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The Cell Cycle


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DNA synthesis

Antimetabolites

DNA

DNA transcription DNA duplication

Mitosis

Alkylating agents

Spindle poisons &

Microtuble Stablizers

Intercalating agents


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Mucositis

Nausea/vomiting

Diarrhea

Cystitis

Sterility

MyalgiaNeuropathy

Alopecia

Pulmonary fibrosis

Cardiotoxicity

Local reaction

Renal failure

Myelosuppression

Phlebitis


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Seen with high rate of infusion of certain drugs alsomore common with new MONOCLONALANTIBODY agents ie RITUXIMAB

Infusion of these agents may take several hours Fever, hypotension, asthma like reactions, pain Premedicate or treat with Dexamthasone, Benadryl,

Panadol

May have to stop infusion temporarily If serious, may have to discontinue agent


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Local inflammatoryreaction

Intact blood return

Short-term injury

Infiltrating surroundingtissue blistering

May be delayed 6-12

hr Severe necrosis Absent of blood return


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Antineoplastic drugs

Amsacrine

Cisplatin (concentrations 0.5

mg/mL)

Dactinomycin

Daunorubicin

Docetaxel (rare) Doxorubicin

Epirubicin

Idarubicin

Mechlorethamine

Mitomycin

Oxaliplatin (rare)

Paclitaxel (rare)

Streptozocin

Trabectedin

Vinblastine

Vincristine

Vindesine

Vinorelbine

Arsenic trioxide

Bleomycin

Bortezomib

Carboplatin/Carmustine

Cisplatin*

Cladribine

Cyclophosphamide

Dacarbazine*

Docetaxel

Etoposide

Fluorouracil/Floxuridine

Gemcitabine Ifosfamide

Liposomal daunorubicin/doxorubicin

Mitoxantrone

Oxaliplatin

Paclitaxel

Thiotepa Topotecan


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Select recent, large IV access with good back flow Fore-arm->dorsum->wrist->anticubital

Avoid sclerosis, thrombosis, or scar sites butterfly needle or plastic cannula should be

secured to the skin with transparent tap Check patency Diluted chemo should be infused with free

flowing DW or NS Central venous catheter..


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Stop the infusion immediately. Do not flush the line Avoid applying pressure to the affected site. Elevate the affected extremity. The catheter/needle should be left in place to

attempt to aspirate fluid from the extravasated

area and to facilitate the administration of anantidote to the local area, if available

Otherwise catheter/needle can be removed

after attempted aspiration of fluid.


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Topical application of ice or cold packs isrecommended for extravasation of allvesicant or irritant drugs except the vincaalkaloids (vincristine, vinblastine, vinorelbine)and epipodophyllotoxins such as etoposide.

Cold application worsens the ulceration Local heating is thought to result in localized

vasodilation and increased blood flow,thereby enhancing drug removal


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Local injection ofsodium thiosulfate forextravasations of mechlorethamine, dacarbazine andcisplatin

Topical application ofdimethylsulfoxide (DMSO) foranthracycline extravasation

A single subcutaneous injection of DMSO formitomycin extravasation, followed by topicalapplication

Local injection ofhyaluronidase has beenrecommended for extravasations of vinca alkaloids,paclitaxel, epipodophyllotoxins, and ifosfamide

Systemic administration ofdexrazoxane following

anthracycline extravasation


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Anthracycline extravasation-IV,SC or IDadministration of corticosteroids at the site

have all been recommended Corticosteroids may worsen the skin damage

from etoposide or vinca alkaloids, and theyare specifically contraindicated in thesesituations.


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Direct Treatment Related:

chemotherapy

- acute

- delayed - anticipatory

- breakthrough N/V

- refractory N/V

radiation therapy

Indirect Treatment Related:

mucositis opiates

antibiotics gastroparesis infection

hyperacidity

anorexia diarrhea

pain

anxiety


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Chemical- direct mucosal injury to GIT(chemotherapy-induced: acute and delayed;opioids)

Vestibular

CNS -increased intracranial pressure, effects onmid-brain vomiting centers

Visceral (direct disease-related sources, abdominalirradiation)


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Starts within thefirst24 hours after chemotherapy

administration

Majority of chemotherapeutic agents induce

emesis approximately 13 hours followingadministration

Most researched type of CINV

Remains common despite dramatically improved

protection

Pisters KMW, Kris MG. In: Principles and Practice of Supportive Oncology. Lippincott-Raven; 1998. Antiemetic Subcommittee of the Multinational Association of

Supportive Care in Cancer.Ann Oncol1998;9:811819.


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Starts 24 hours or more afterchemotherapyadministration

First defined with high doses of cisplatin but known to

occur with other chemotherapy agents

Carboplatin

Cyclophosphamide

Doxorubicin

Epirubicin

Anthracyclines

Mechanism not known; appears to differ from acute

emesis

Berger AM et al. In: Cancer: Principles and Practice of Oncology. 6th ed. Lippincott Williams & Wilkins, 2001:28692880. Antiemetic Subcommittee ofthe Multinational Association of Supportive Care in Cancer.Ann Oncol1998;9:811819.


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No AcuteCINV

No Delayed76%

Delayed

24%

Yes Acute

CINV

No Delayed20%

Delayed80%


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Worst nausea seen with cysplatin, High dose

cyclophosphamide, Doxorubicin, Epirubicin,

Prokinetics, Antiemetics, Lorazepam, Haloperidol,Steroids

Diet (avoid fried, fatty foods)

Smaller meals


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Chemotherapy injure all rapidly dividing cells Presents with loss of taste, mouth sores,

inflammation and sometimes sloughing ofmucosa anywhere in GIT or Respiratory tract Oral complications seen to arise in 40% of

patients receiving therapies Source of bacteriemia


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Simple oral mucositis treated with mouth rinse/ice cubes

Salt water gargles

TOPICAL ANALGESIA ie xylocaine

Systemic analgesia e.g IV morphine Nystatin

Stomatitis cocktail/Magic mouthwash: 1:1:1 antacid

solution containing aluminum hydroxide, magnesiumhydroxide/viscouslidocaine/diphenhydramine(benadryl)

Multivitamines,Zn


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Heart burn/ gastritis

Treated with regular use of PPI, Antacids, sucralfate

Severe mucositis with esophagitis, diarrhoea,sloughing of mucosa need aggressive supportivemeasures including Bowel rest, IV fluids to maintain

hydration and electrolyte imbalances

TPN


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Chemotherpy induced mucosal injury causes

increased fluid secretion by the intestine.

Seen in upto 45% of cases

Risk factors include: known colitis, concomitantirradiation, Elderly, more frequently seen with GImalignancies

Severe with 5-FU ,sometimes need Atropine


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Usually self limiting Supportive management Fluids & Electrolytes

Nutrition

Avoid problem foods and drugs, soft diet Medication management

Opioids

Loperamide (imodium) more effective 4 mg statthen 2mg q4hrly till formed stools *

Diphenoxylate(Lomotil)

*(r/o infective diarrhoea/C.Diff)


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If severe, Ocreotide (Sandostatin)

Decreases fluid output from bowel 100mcg sc TID

Growth hormone analogue-decreases all salivarygland secretions Side-effects include gall bladder problems,

dysglycemia, hypothyroidism, bradycardia

Antibiotics may be considered e.g if C.DIFF +ve

oral metronidazoleoral vancomycin

oral CIPRO


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Alkylating agents

Cisplatin

Ifosfamide

Carmustine Carboplatin

Malphalan

Antimetabolites

Methotrexate

Gemcitabine

Other

Mitomycin C


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Cisplatin Fractionate dose

Continuous IV

Adequate hydration

Use mannitol (increaseurine volume)

Prevent dehydration

Amifostine

Carboplatin substitute (notfor all case esp in germ celltumor

Metrotrexate Adequate hydration

Alkalinize of urine

Leucovorin rescue

Ifosfamide/cycloph Fractionated doses

Hydration Monitor fluid retention

(body weight)


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Agents Ifosfamide, cyclophosphamide in high dose acrolein

accumulation in bladder

Clinical presentation Onset : 2-3 days

Hematuria, dysuria

Prevention

MESNA (2-merceptoethane sodium sulphonate) 100-160% of dose + adequate hydration 3L/sq m/day


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Stop chemotherapy

Hydration &diuresis

Bladder irrigation 300-1000ml/h

Cyctoscopy

Adequate platelets

Chemical agents e.g Alum, Formaline

Selective embolization Surgical intervention etc


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High dose cytarabine cerebellar toxicity

L-asparaginase drowsiness, stupor

Cisplatin ototoxic, ataxia

Etoposide

Vinca alkaloidjaw pain,cranial nerve pulsies

Procarbazine

Metrotrexate acute arachnoiditis Oxaliplatin sensory neurotoxic (cold trigger

symptom parathesia


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Peripheral Neuropathy

Numbness Sense of touch is distorted- ordinary touch can

be unpleasant or painful.

Burning or prickling feeling without stimulus Decreased touch sensation Difficulty sensing the position, location,

orientation, and movement of the body and itsparts (Proprioception)

Glove and stocking distribution


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Seen commonly with Vincristine, Vinblastinand cisplatin

Usually temporary Sometimes respond to dose alteration or

stopping some drugs Gabapentine, Amityptyline, Carbamazapine

may help in severe cases


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Risk factor

Cumulative dose: bleomycin, busulfan,BCNU

Age: bleomycin

Radiotherapy: bleomycin, busulfan, mitomycin,cyclophosphamide, doxorubicin, actinomycin

Oxygen therapy: bleomycin, cyclophosphamide,mitomycin

Prevention----Avoid risk factors, free radical scavanger,early detection Treatment----corticosteroids, diuretics


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Anthracyclines

Cyclophosphamide

5-FU Trastuzumab (Herceptin)

Bevacizumab

Cisplatinin (Platinol)


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Congestive heart failure (mortality >20%) Risk factors

Life time Cumulative dose (> 450 mg/m2)

Dosing schedule- infusion lesser risk than bolus

Age (>65 or


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Mild ECG abnormalities Arrhythmias (both supraventricular and

ventricular)

Heart block (including Mobitz type II seconddegree AV block and complete heart block),ventricular dysfunction

High plasma brain natriuretic peptide (a markerof increased cardiac filling pressures and heart

failure) Pericarditis-myocarditis syndrome (particularly

with mitoxantron)


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In adults, chronic anthracycline-relatedcardiotoxicity typically presents early, within one

year after termination of chemotherapy.

The peak time for the appearance of symptoms ofheart failure is about three months after the last

anthracycline dose

Mortality in these early series was high (60 percent);


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Avoiding anthracyclines Lowering cumulative dose Lowering peak dose

2nd

generation anthracyclines (Idarubicin,epirubicin, mitoxantrone) Early detection of subclinical cardiotoxicity

(Echocardiography) Oxygen free radical scavengers vit.E, C, Liposomal encapsulation Dexrazoxane ACE inhibitors and Beta blockers


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Local cutaneous reactionafter chemotherapy

Seen on palms, finger, soles

2-12 days after chemo

Tingling, burning of palms,hand, feet

Pain, peeling Resolution in 7-14 days after

stopping medication


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Common in high dose therapy, prolongedinfusion, liposomal forms

Agents

Capecitabine Cytarabine

Docetaxel

Daunorubicin

Doxorubicin(liposomal)

5-FU (infusion)

MTX


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Management

Dose reduction

Topical wound care, cold cream base & emollients

Pain management

Steroid creams

Pyridoxine

Avoid heat and pressure, avoid tight fitting shoes


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Anthracyclins Etoposide Cyclophosphamide

Taxanes Ifosphamide Vindesine Vinorelbine

Topotecan


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Myelosuppression

Febrile neutropenia Anemia Bleeding -Thrombocytopenia


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Febrile neutropenia

Monitor fever (>38.5 C)

ANC < 1.0 x 109 /L

Anemia Hb < 10 g/dL

Thrombocytopenia

Platelet < 20,000 / mm3

Antibiotics/antifungal/antiviral prophylaxis

(CSF prophylaxis)

Blood transfusion (Epoitin alpha)

Platelet transfusion


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Multiple white bands

in the nails,representing periods

of growth arrest


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Rash

Topical and/oral

antibiotics

Topical and/or oral

antihistamines Cool compresses Petroleum jelly, silver

sulfadiazine ointment

for ulcerative lesions

Avoid sun, heat &

humidity

Use mild soaps

Water based sunscreens/other products


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Malignancy diagnosis can be overwhelming The discussion of treatments and adverse

effects can also be overwhelming Anxiety, depression, fatigue related to

diagnosis and treatments LOTS of information regarding treatments


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Gaining Control by giving up control.(Dr. B. Rotella)

Daily routine goes upside down Changing work routinemissing work for

weeks, months or permanently Income changes


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The inability to forget is infinitely moredevastating than the inability to remember.

Mark Twain

Hard to forget some of the stressful timesone goes through Getting through months of chemotherapy is

very difficult task Just surviving each day step by step Need a team approach, social worker,

supportive care coordinators etc


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approach to the management of adverse effects of.pptx

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