Med Onc Jnr Handbook

8/19/2019 Med Onc Jnr Handbook

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Introduction:

Welcome to the department of medical oncology at the Townsville Cancer Centre. By

the end of the term, you should be able to identify and manage common side effects of

chemotherapy and radiotherapy in the land of general practice, emergency

departments and rural hospitals and general medical wards. You will also have some

understanding of treatment principles and aims of cancer therapy for common

malignancies. This handbook is meant for the use of resident medical officers and

basic physician trainees. It may also be useful to advanced trainees in their first few

months of training.. We hope that this experience will give you the skills to deal with

cancer patients with positive and empathetic approach.

If you are encountering emotional difficulties when dealing with poor prognosis,

please talk to one of us earlier in the term to learn ways to deal with it effectively.

Enjoy the medical oncology rotation.

Regards ,

Consultant Medical Oncologists.


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Table of contents:

1. Introduction of senior medical staff-----------------------------------------------------4

2. Weekly time table of clinical and educational activities-----------------------------4

3. Educational aims and Duties ------------------------------------------------------------5

4. Principles of management of patients on chemotherapy:---------------------------6

Assessing fitness for chemotherapy------------------------------------------------------- 6

Important practice points for common drugs--------------------------------------- ---- 9

Antiemesis ---------------------------------------------------------------------------------- 12

Febrile neutropenia------------------------------------------------------------------------- 15

Extravasation------------------------------------------------------------------------------- 18

Premedications for selected drugs ------------------------------------------------------- 19

5. Medical emergencies---------------------------------------------------------------------21

6. Summary of management of common cancers:------------------------------------23

Anus------------------------------------------------------------------------------------------- 23

Bladder---------------------------------------------------------------------------------------- 23

Breast------------------------------------------------------------------------------------------ 24 Carcinoma of unknown primary----------------------------------------------------------- 26

Cervix------------------------------------------------------------------------------------------ 26

Colo rectum----------------------------------------------------------------------------------- 26

GBM------------------------------------------------------------------------------------------- 28

Germ cell tumours---------------------------------------------------------------------------- 28

Head and neck-------------------------------------------------------------------------------- 30

Lung cancer----------------------------------------------------------------------------------- 30 Melanoma------------------------------------------------------------------------------------- 31

Mesothelioma--------------------------------------------------------------------------------- 31

Oesophagus------------------------------------------------------------------------------------ 32

Ovary------------------------------------------------------------------------------------------- 33

Pancreas---------------------------------------------------------------------------------------- 33

Prostate----------------------------------------------------------------------------------------- 34

Stomach and distal oesophagus------------------------------------------------------------- 33

7. Symptom control --------------------------------------------------------------------------- 35


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Senior Medical Staff:

1. A/Prof Sabe Sabesan,BMBS( Flinders), FRACP,Director and Senior Staff Specialist.Clinical Dean, Townsville Clinical School.

2. Dr Suresh varma,MBBS,MD,DM, FRACP,Senior Staff Specialist and adjunct senior lecturer.

3. Dr Abhishek Joshi,MBBS,MD,DM,ECMO,FRACP.Staff Specialist and senior lecturer.

4. Dr Zulfiquer Otty, MBBS, MD,MRCP,FRACP,Staff specialist and adjunct senior lecturer.

Weekly Timetable:

Time Mon Tues Wed Thurs Fri 0745 ‐0830 GI MDT

(0800 ‐0900) 4 Breast 1 MDT Gyne onc 2

( monthly) 0900 ‐1200 Clinics

SS, AJ Clinic SV

Clinic CM, SV

Clinic SS,CM

Clinic SV

1230 ‐1330 Grand rounds

Radiology meeting

1330 ‐ Clinic H&N clinic 4 Skin MDT

1400‐1500

clinic

Medonc

tutes Journal

Club

1500 ‐1600 Reg training 1600 ‐1700 Neuro MDT

monthly Lung MDT 4

1. pathology conference room, 2. NICU conference room, 3. onc conferenceroom, 4. Oncology conference room.

2. Consultant ward rounds are 2-3 times a week and more often for sick patients.


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Educational aims for this rotation:

1. Management of complications of chemotherapy

2. Familiarise with common chemotherapy regimens

3. Management of medical emergencies

4. Management of quality of life issues

5. Understanding of psychosocial issues related to cancer patients- discussing prognosis, breaking bad news, family meetings etc

6. Understanding of curative vs palliative intent therapy

7. Familiarise with the management of common malignancies includingmultidisciplinary approach

Tasks:

1. Managing inpatients – routine inpatient care, ward consultations, weekendroster ( it is the responsibility of the registrars to do this roster).

Prior to consultant ward rounds, results should be available for imagingstudies, histology and blood tests.

(For interns, all the procedures except IV cannulation need to besupervised by registrars or consultants).

2. Review of day unit patients

3. Review of clinic patients

4. Phone consults from GPs, other staff and the patients

Day unit and clinic patient review:

1. To assess fitness for chemotherapy2. To assess symptoms and side effects of treatment.3. To address new concerns4. To assess for treatment response-

a. tumour markers b. scans- performed after 2-3 cycles,

5. To update chemotherapy scripts


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Principles of management of patients on chemotherapy

Assessing fitness for chemotherapyFitness for chemotherapy depends on three factors:

performance status the type and severity of side effects from previous cycles of chemotherapy (if

any) blood parameters Co-morbidities

If cure is the aim, it is usual to accept mild-to-moderate, non-life-threateningtoxicities and continue treatment without delaying or reducing the dosage tominimise side effects. However, in patients with incurable metastatic disease wherequality of life is paramount, dose delays or dose reductions are necessary.

Performance status

This is graded using the Eastern Cooperative Oncology Group (ECOG) scale.

Grade ECOG performance status0 Fully active, able to carry on all pre-disease performance without

restriction

1 Restricted in strenuous physical activity but able to carry out work ofa light sedentary nature

2 Ambulatory and capable of all self-care but unable to carry out anywork activities

3 Capable of only limited self-care, confined to bed or chair more than50% of waking hours

4 Completely disabled, cannot carry on any self-care, totally confinedto bed or chair

Usually, patients with ECOG grade > 2 are not fit for chemotherapy. The exception is

chemotherapy-sensitive cancers such as lymphoma and small cell lung cancers. Thedecision to offer chemotherapy must be individualised depending upon factors likeage of the patient, comorbidities, etc; For example, a young patient with metastatic

breast cancer with poor performance status could still be offered systemic treatments.Targeted agents and endocrine therapy are usually tolerated better than chemotherapy.

Toxicity from previous cycles of chemotherapy :

Clinicians must assess whether a side effect is affecting function or is life threatening:

First, determine the type and severity of side effects.


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For example, in patients with early breast cancers undergoing taxane chemotherapy,mild peripheral neuropathy is acceptable. However, in patients undergoingfluorouracil-based therapy, ongoing or severe diarrhoea necessitates a dose delay anddose reduction of subsequent cycles.

Mid-cycle neutropenic fever usually requires dose reduction of the subsequent cycleunless the cancer is curable. If the cancer is curable or a substantial duration ofremission is expected, prophylactic colony stimulating factors such as pegfilgrastim(neulasta) and/or antibiotics can reduce the risk of opportunistic infection.

Next, determine the effects on important organs, such as:

Fertility. Discuss semen cryopreservation with men. There are no proven useful procedures for women, however preservation of egg, embryo and a piece ofovary is offered by some fertility groups. Women who wish to discuss thisoption should be referred to a fertility specialist.

Renal function, liver functions. Cardiac function. This may affect the dosage of anthracyclines (check ejection

fraction before treatment begins and after every 2–3 cycles) and trastuzumab(check ejection fraction before treatment begins and every 3 months duringtherapy).

Toxicity is graded according to NCI common terminology criteria for adverse events 1

1.Blood parameters:

(a) Requires haematological and non-haematological parameters.For most regimens, a neutrophil count >1.5 x 10 9/L and platelet count > 100 x 10 9/Lare needed for safe administration of chemotherapy. For weekly Taxol, neutrophilcount of >1.0 x 109/L and platelet count of >75 x 109/L is acceptable.

Some regimens, like single agent bleomycin and vincristine, are not myelotoxic andadministration is not affected by blood counts.

Renal function is important for cisplatin and carboplatin and liver function fordocetaxel. .Magnesium levels esp for cisplatin.Calcium levels for denosumab.

Action- withhold treatment until recovery, then dose delay and/or dosereduction.

(b) Pregnancy test: For women of child bearing potential, if they are not sure ofpregnancy status, perform beta HCG before initiating treatment.


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2:Non-haematological toxicity

( Also see the summary of common SEs for seleceted drugs in page11)

a. Diarrhoea – mainly 5FU based, Irinotecan, Oxaliplatin, Taxotereaction- low threshold for withholding therapy if diarrhoea the day before

or moderate diarrhoea for longer than expected duration or nocturnaldiarrhoea.

b. Mucositis/mouth care

c. EmesisAction-( see antiemetics) change class, add another agent or dosereduction.

d. Skin Rash

e. Neuropathy- Cisplatin, Oxaliplatin, Taxanes, Vinca alkaloidsdose delays or reduction if neuropathy persist or interferes with function.

f. Autotoxicity- Cisplatin

g. Renal impairment- Cisplatin.Action- prior to most agents, need to check creatinine especially if they arerenally cleared.Carboplatin- dose adjusted based on creatinine.

h. Pulmonary toxixcity- bleomycin, methotrexate

3. physical examination-routine exam and mouth, central lines, lymph nodes andsigns of recurrence and side effects.

When to s top cancer treatmentA decision to stop treatment prematurely depends on the aim of the treatment.

For curable cancers, it is acceptable to continue treatment with dose modifications.However, life threatening or severe dose limiting toxicities usually necessitatecessation of treatment (eg. moderate to severe peripheral neuropathy with taxanes andoxaliplatin, severe enteritis from fluorouracil). Alternative regimens are sometimesavailable.

If the cancer is incurable and the toxicities severely interfere with the activities of

daily living, treatment may have to be stopped.


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Deteriorating performance status and organ function usually require cessation oftreatment. Ongoing neutropenia or thrombocytopenia typically means the patient isnot going to handle further chemotherapy.

If the cancer is not responding to the therapy after 2–3 cycles, cessation of the sametherapy is advised.In case of patients with metastatic disease, palliative care team referral is done evenwhen they are on active treatment , to improve symptom management and supportivecare.

Important practice points for common drugs:

1. Adriamycin/ Epirubicin - look at cumulative dose, perform cardiac function

every 2-3cycles.

2. Bleomycin - Lung function every 3 weeks.

3. Cisplatin - renal function, Mg levels, peripheral neuropathy, hearing loss/tinnitus.

4. Carboplatin - adjust dose based on renal function.

Dose= AUC x (GFR+25).

5. 5-FU - diarrhoea. In severe cases, it can be life threatening.

No diarrhoea on the day and the previous day of chemo.

If diarrhoea daily, consider dose reduction.

5FU could also cause coronary Artery spasm.

In severe 5FU enteritis, admission for bowel rest +/-TPN along with aggressive

anti diarrhoeal and antibiotics may be required.

6. Gemcitabine - pneumonitis, peripheral edema.

7. Irinotecan - need to have normal bilirubin. diarrhoea, flushing- acute symptoms

could settle with atropine with chemotherapy. For chronic symptoms,

dose reduction is necessary.8. Taxol/ Paclitaxel - peripheral neuropathy, flu like symptoms

9. Taxotere/Docetaxel - adequate liver function, peripheral edema, neuropathy, rash.

10. Oxaliplatin - cold induced paresthesia( acceptable), but signs of peripheral

neuropathy may be dose limiting. Laryngo spasm (cold induced)

and bronchospasm are other acute side effects.

11. Cyclophosphamide/ Ifosfamide - renal function, hydration, confusion from

encephalopathy.12. Xeloda - mucositis, hand foot syndrome, rash, angina, diarrhoea.


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13. Herceptin - cardiac function every 3 months.

14. Erbitux - acneform rash. Presence of k-ras mutation is associated with no

response from erbitux.

15. methotrexate - folinic acid rescue.

16. Caelyx/ Liposomal doxorubicin - rash, hand foot syndrome, cardiac function.

17. Avastin - hypertension and proteinuria.18. Denosumab - prolonged hypocalcaemia(require calcium suppliments).19. Vemurafenib (b-raf inhibitor)- rash,squamous cell carcinomas of skin.20. Zelodronic acid -renal function, hypocalcaemia, requires dose reduction

for renal impairment. Need calcium suppliments

Alopecia- not with every drug.Common with breast, ovarian, sarcoma, small cell, lung(Carbo/Taxol) cancer and

testicular regimens

COMMON CHEMOTHERAPY ABBREVIATIONSBREAST CANCERTAC : Docetaxel, Adriamycin, CyclophosphamideFEC : 5Fluorouracil, Epirubicin, CyclophosphamideAC : Adriamycin, Cyclophosphamide

COLO-RECTAL CANCER

FOLFOX : Oxaliplatin, Continious infusion 5Fluorouracil and LeucovorinXELOX : Oxaliplatin, CapecitabineFOLFIRI : Irinotecan, Continious infusion 5 Fluorouracil and LeucovirinXELIRI : Irinotecan, Capecitabine

GASTRIC/LOWER OESOPHAGEALECF : Epirubicin, Cisplatin, 5 FluorouracilECX : Epirubicin, Cisplatin, CapecitabineEOX : Epirubicin, Oxaliplatin, Capecitabine

HEAD AND NECK CANCER

TPF : Docetaxel, Cisplatin, 5 Flurouracil

TESTICULAR CANCERBEP : Bleomycin, Etoposide, CisplatinTIP : Ifosfamide, Paclitaxel, Cisplatin


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Common side effects of oncology medications

Combinations are more likely to cause myelosuppression and emesis than single agents.Myelosuppression Mucositis Enteritis Alopecia Cardiac Renal Neuropathy

Anthracyclines ++ + ++ + Bleomycin Capecitabine ++ ++ angina

Carboplatin ++ +Cisplatin + ++ ++Cyclophosphamide + + + 5FU ++ ++ angina Fotemustine ++ +Gemcitabine + + Irinotecan + ++ + Oxaliplatin(combinedwith 5FU)

+ + ++ angina ++

Paclitaxel + ++ ++Taxotere/Docetaxel + + ++ ++ permetexed + +

Monoclonal antibodies and small moleculesInfusionreaction

Anaphylaxis cardiac rash thyroid Proteinuria diarrh

Trastuzumab + + +Bevaczuzumab + + + Cetuximab + + ++Sunitinib ++ + +

Erlotinib ++


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Chemotherapy related emesis :

Causes of nausea and vomiting in patients receiving chemotherapy:1. Chemotherapy related

2. Other causes like gastro-oesophageal reflux disease or medications likeopioids.

Pathways by which chemotherapeutic agents may produce anemetic response 2

Chemotherapy-induced emesis results from stimulation of a multistep reflex pathwaythat is controlled by the brain and triggered by afferent impulses to the vomitingcenter from the chemoreceptor trigger zone, gastrointestinal tract (by way of vagalafferent fibers), and possibly, the cerebral cortex.


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Emetogenic potential of chemotherapy agents

High (>90%) Moderate (60-90% Moderate(30-60%)

Low(10-30%)

Minimal

Cisplatin>50mg/m2

Carboplatin Cyclophos60mg/m2 Doxorubicin20-60mg/m2

Caelyx Cetuximab

Epirubicin>90mg/m2 Epirubicin


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Antiemetics:

1. Neurokinin 1 receptor antagonist- Aprepitant (emend), fosaprepitant

2. 5HT3 antagonists: ondansetron (zofran), granisetron & palonosetron(aloxi)

3. Dopamine antagonists : 1.Phenothiazines- prochlorperazine, 2. Benzamides:Metoclopromide. 3.butyrophenons-haloperidol

4. Glucocorticoids:- good for early and delayed nausea.

5. Anti histamines:Promethazine

6. Benzodiazepins: Lorazepam-good for anticipatory emesis

High emetogenic drugs and anthracycline containing regimens for breast

cancer :3

Emend (Aprepitant)-

Day 1- 1 hour pre chemo 125 mg orally,day 2 and 3- 80 mg daily.

Plus

Aloxi (Palonosetron) 250 mcg IV on Day 1 only or Zofran ( Ondansetron) 8mgbd for 2-3 days starting the night of chemotherapy.

Plus

Dexamethasone- 8-12 mg IV pre-chemo and 8mg oral mane for 2-3 days.

NB- for patients who experience sudden decline in well being when steroids arestopped, a weaning off regimen might be useful.

Maxolon- 10 mg Q6H PRN.

NB- Zofran can be constipating- so warn pts about prevention of constipation. Donot prescribe take-home zofran after Aloxi.

Moderately emetogenic drugs or combination of drugs:

Aloxi (Palonosetron) 250 mcg IV on day 1.Plus

Dexamethasone- 8 mg IV pre-chemo and 8mg oral mane 2-3 days

NB- for patients who experience sudden decline in well being when steroids arestopped, a weaning off regimen might be useful.


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Emend can be added to the above regimen if the patients experience nausea &vomiting after moderately emetogenic chemotherapy.

Maxolon- 10 mg Q6H PRN.

.

Mildly emetogenic drugs:

Usually maxolon premedication with maxolon 10 mg Q6H PRN would be enough. Ifnausea not controlled with maxolon, might have to treat it like moderate drugs afterexcluding other causes of nausea. Eg- GORD.

If nausea persists, look for other causes.Addition of lorazepam 1 mg Q6H PRN useful esp for anxious patients

INFECTIONS

Neutropenic Fever 4, 5

It is a medical emergency. It is the responsibility of the MO to ensure promptantibiotic administration.

With diarrhoea and neutropenia, even if afebrile, use the same protocol.

Definitions

A single oral temperature of 38.3 0 A temperature ≥ 38 0 on two occasions over 1 hour ANC ≤ 500 or less ≤ 1000/µl with predicted rapid decline to less than 500/µl

Septic Work-Up

Physical examination

Blood cultures x 2 sets (venipuncture and indwelling venous catheter if present),urine C&S, cultures from any suspected sites, CXR .)

Treatment of Neutropenic Fever : 6 Antibiotics

Cefepime* IV 2 g BDor Piperacillin/ tazobactam (Tazocin) 4.5 gm Q6-8 hourlyor Ceftazidime 2 gm 8 hourly.

In patients with hypersensitivity to pencillins, seek expert advice.


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Modifications

Add Gentamycin 5-7 mg/kg/IV if patient is unstable or has pneumoniaor in suspected gram-negative infection.

Add Vancomycin 1 g 12 hourly if clinically unstable, gram positive bloodcultures before antibiotics, severe mucositis present, already on Quinolone

prophylaxis, a catheter associated cellulitis or tunnel infection, high prevalenceof Methicillin-resistant staph aureus.

Metronidazole for abdominal symptoms or suspected C. difficile infection.

Persistent neutropenic fever on D5 – add antifungal therapy (Amphotericin B0.5mg/kg/day or Fluconazole 400mg/day)- But discuss with consultants first.

Duration of Antibiotics (variable) Low risk patient (clinically well, stable signs, no mucositis, ANC >100/µL, rising

ANC, afebrile within 3 days of starting antibiotics, negative cultures) considerearly discharge on Day 4 on oral Ciprofloxacin 750mg BD for 5 days or ceaseantibiotics altogether when ANC >500/µL

High risk patients who become afebrile within 3 days, should continue parenteralantibiotics, targeted to the specific pathogen, until resolution of neutropenia

Specific pathogens need to be treated according to therapeutic guidelines

Patients with any of the following characteristics are considered to be at high risk for seriouscomplications during episodes of neutropenic fever:

Neutropenia (absolute neutrophil count 7 days*

Presence of any comorbid medical problems, including, but not limited to:

Hemodynamic instability

Oral or gastrointestinal mucositis that interferes with swallowing or causes severe diarrhea Gastrointestinal symptoms, including abdominal pain, nausea and vomiting, or diarrhea

Neurologic or mental status changes of new onset

Intravascular catheter infection, especially catheter tunnel infection

New pulmonary infiltrate or hypoxemia

Underlying chronic lung disease

Complex infection at the time of presentation


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Inpatient status at the time of development of fever

Uncontrolled or progressive cancer Δ

Evidence of hepatic insufficiency (defined as aminotransferase levels >5 times normal values) orrenal insufficiency (defined as a creatinine clearance of 1000 µL

Add Vancomycin 1 g 12 hourly

Re-evaluate on Day 5

Febrile Afebrile

Add Amphotericin B (1-1.5 mg/kg/day) or Continue antibiotics for 5 days

Fluconazole 400mg/day or until neutrophils >1000 µL

Consider non infective causes of fever


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Colony stimulating factors (GCSF) are generally not recommended in managementof febrile neutropaenia, with some exceptions.

Catheter-related infections;

Catheter removal is recommended in addition to antibiotic therapy for at least 14days. But if the infection is caused by coagulase-negative staphylococci and isimportant to save the line, catheter could be retained using systemic antibiotics.

EXTRAVASATION OF CHEMOTHERPAY DRUGS 7

If it does occur, proper documentation should include the time, site of line insertion,

needle

size, estimated amount of extravasated drug, technique used to manage the

extravasation, appearance of site, photograph, patients comments, and notification of

physician.

Management

Stop infusion. Before removing cannula attempt to aspirate some of extravasated

fluid. If antidote exists give it both IV through cannula and by SC infiltration (see

table).

Intermittent local cooling is recommended, except for vinca alkaloids (warming

packs). Rest and elevate the affected site for 48 hours. Telephone contact daily and

assess need for plastic surgery.


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Antidotes for Ves icant and Irr it ant Dr ugs

Table 3

Chemotherapy agent Pharmacologicantidote

Nonpharmacologic Antidote

Method of Administration

Mechlorethamine

(nitrogen mustard)

Cisplatin (largeextravasation)

Sodium

thiosulfate

None Prepare 1/6 molar

solution: if 10%Na

thiosulfate solution, mix 4

mL with 6 mL sterile water

for injection.

Through existing IV line,

inject 2 mL for every 1 mg

extravasated. Inject SC if

needle is removed.

Vincristine

Vinblastine

Vindesine

Etoposide

Vinorelbine

Hyaluronidase Warm packs. 15-20

minutes at least four

times/day for the first 24-

48 hours and elevate

Prepare hyaluronidase,

150 units/mL with 1-3 mL

saline. Inject through

existing IV line, 1 mL for

each 1 mL infiltrated.

Inject SC if needle is

removed.

Doxorubicin

(Adriamycin)

Daunorubicin

Idarubicin

Mitomycin C

DMSO Ice packs Apply cold pad with

circulating ice water pack

or cryogel pack for 15-20

minutes at least four

times/day for first 24-48

hours. Some benefit of

99% dimethyl sulfoxide

(DMSO) 1-2 mL applied to

site every 6 hours.

Paclitaxel

Docetaxel

Hyaluronidase Ice packs As for Vinca alkaloids.

Premedications to prevent allergic reactionsPaclitaxel Premedications

Recommended schedule:

- Dexamethasone 20 mg oral, 12 hours and 6 hours before Paclitaxel (in practice

the night before and the morning of treatment).

- Promethazine 25 mg IV 30-60 minutes before therapy.

- Ranitidine 50 mg IV 30-60 minutes before therapy.

- Additional Dexamethasone IV as antiemetic depending if Paclitaxel givenalone (4mg IV) or in combination with other drugs.


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Modified regimen (in cases where the patient forgets to take premedication, or 2 nd

and subsequent cycles where no hypersensitivity reaction occurred with 1 st

treatment and steroids are not appropriate):

- Dexamethasone IV 20 mg 30 minutes before Paclitaxel.

- Promethazine IV 25 mg IV 30-60 minutes before therapy.

- Ranitidine 50 mg IV 30-60 minutes before therapy.

(Product Information, 2001)

(Markman M. J Clin Oncol 15(12): 3517, 1997.)

(Kintzel PE. Ann Pharmacother 35:1114-7, 2001.)

Modified schedule for weekly regimen (where steroids are not appropriate):

1st Treatment - Dexamethasone 12 mg IV

- Promethazine 25mg IV

- Ranitidine 50mg IV

If no hypersensitivity reaction, subsequent treatments may be given without

premedications.

(Quock J. Proc ASCO 18 abstr 635, 1999.)

Docetaxel Premedications

Recommended schedule for 3 weekly regimen:

- Dexamethasone 8mg BD oral x 6 doses (starting night before treatment)

- Additional Dexamethasone IV as antiemetic depending if Docetaxel used

alone (4mg IV) or in combination with other drugs.

(Product Information, 2001.)

Schedule for weekly regimen:

- Dexamethasone 8mg oral BD x 3 doses (starting night before treatment)

(Jackisch C. Proc ASCO 19 abstr 417, 2000.)


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Monoclonal Antibodies

Trastuzumab (Herceptin) may cause fever and chills, chest tightness and

tachycardia with 1 st infusion.

Rituximab (Mabthera) may cause asthenia, chills, bronchospasm, hypotension,angioedema. Premedicate with Paracetamol 1 g QID, Promethazine 25 mg IV

and Hydrocortisone 200 mg IV 30-60 minutes prior to drug.

Cetuximab requires phenergan 12.5mg or 25 mg prior to infusion.

Medical Oncology Emergencies:Management of Neutropaenic fever is discussed above.

Spinal Cord-compression

neurological symptoms and signs consistent with spinal cord compression necessitates

1.urgent review and MRI of spine.2.Urgent neurosurgical and or radiotherapy referral3. start Dexamethasone8mg IV stat , followed by 16-24

mg daily in divided doses.

SVC Obstruction :

If the patient presents with stridor or respiratory compromise , emergency treatmentwith endovascular stent and Radiotherapy is required.In other cases, a histological diagnosis is required prior to initiating specifictreatment.

In chemotherapy-sensitive malignancies like small –cell lung cancer, germ celltumour or lymphoma, systemic chemotherapy is usually the treatment. In most othertum ours, including non-small cell lung cancer, Radiotherapy is the preferredtreatment.Endovascular stenting prived rapid relief of symptoms.

Hypercalcemia:

Saline hydration.IV zolendronate.IV frusemide if fluid overload.

Steroids useful in hypercalcaemia due to lymphoma.s/c calcitonin.


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Infusion reactions and other acute reactions

Mild to moderate infusion reactions with no features of anaphylaxis-IV hydrocortisone and phenergan. Stop infusion till reaction subsides and restart at a

lower rate, with close monitoring.

Severe infusion reactions and anaphylaxis (hypotension, angioedema,bronchospasm,generalised urticaria)- Resuscitaion with epinephrine, hydrocortisone,phergan,ranitidine and fluids.DO NOT RE-CHALLENGE.

Notes:


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Summary of management of common cancers: 8,9

This section outlines the principles behind the management of common cancers.

For metastatic cancers, enrolment into a clinical trial is the best treatmentoption.EviQ and NCCN guidelines offer up to date practical guidelines for mostcancers.

Anal cancer-

Most cancers are treated with chemoradiation.*For chemo radiation - mitomycin and 5FU.

Contraindication- ischaemic heart disease, severe diarhhoea.

*Metastasis - same regimen or cisplatin- 5FU.

Bladder- Non-muscle invasive disease is treated with surgery and adjuvant intravesicaltherapies (eg. intravesical therapy with BCG).

Muscle invasive disease is treated with surgery. Pre-op chemotherapy improves

survival.

Inoperable disease may be managed with:

radiotherapy with or without radiosensitising chemotherapy chemotherapy alone (platinum and gemcitabine), or palliative care alone.

Metastatic disease is managed with above chemotherapy regimens or palliative carealone.

Carbo AUC 5 or Cisplatin Day 1 and Gem 1000mg/m2 D1 and Day8.


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Breast cancer-

Early breast cancers:

(Includes axillary node positive disease)

Mostly curative intent therapy.Post operative systemic treatment depends on oestrogen and/ or progestogen receptorstatus, Her 2 status and prognosis ( risk of systemic relapse).

Prognosis- depends on prognostic factors.Size, age, grade, axillary nodes, receptor status and lymphovascular invasion.

Low risk average High risksize 2 cmage


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In post-menopausal patients who are on treatment with tamoxifen, switching to AIafter 2-3 years is recommended .5 additional years of aromatase inhibitors after 5 years of tamoxifen improves survivalin high-risk patients. 10 years of tamoxifen improves survival compared to 5 years oftamoxifen.

For patients on AIs and documented osteopaenia (T score less than 2.00), twice yearlyZometa decreases the rate of decline in bone density. Thay are also encouraged totake regular calcium and vitamin D tablets. Usually DEXA scans are done yearly totwo yearly. Chemotherapy regimens -Lower risk average risk- r4 cycles of Taxotere/Cyclophosphamide (TC), or 4x ACAverage risk- usually 6 cycles of anthracyclines (FAC)High risk- TAC x6 or FECx3 then Taxoterex3 (PACS 01).Her 2 positive disease-Herceptin is combined with Taxanes and not with anthracyclines because of cardiactoxicity.In Her2 positive disease, a non-anthracycline regimen ,TCarboH is an alternative 10

Neulasta- if cycles delayed because of neutropenia or had neutropenic fever. PACS01 and TAC needs Neulasta day2 regardless of neutropenia. All breast canceradjuvant regimens need Emend as well as 5HT3 antagonist and dexamethasone forantiemetic prophylaxis.

Neoadjuvant chemotherapy:

Chemotherapy regimens are similar to adjuvant regimens. Assess response clinicallyor by ultrasound.More effective in triple negative or her 2 positive disease.

Post operative radiotherapy:

After lumpectomy, radiotherapy decreases local recurrence rates.

After mastectomy, indications include:

close or positive margins >4 axillary nodes involved tumour size >5 cm extensive lymphovascular invasion.

Radiotherapy is given after the chemotherapy is completed.

Locally advanced and inflammatory breast cancers

The cure rate is much lower than with early breast cancers.Chemotherapy is given before surgery to reduce the size of the primary and eradicate

micrometastases (see above for regimens).Radiotherapy is given after surgery.


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Metastatic breast cancer-

• ER/PR positive bone only mets- hormones +/- Herceptin.•Bone mets also benefit from monthly Bisphosphonates or Denosumab to reduce pain,

skeletal events and hypercalcemia.•First line chemotherapy is usually Taxanes or anthracyclines usually as single agentor with cyclo. If the disease is aggressive and of high volume that threatens survival,could offer triple agent combination like FEC or TAC.•In Her 2 positive disease, Taxanes can be combined with Herceptin as initialtreatment. Herceptin is continued as long as it is effective. Once herceptin fails,lapatinib is second-line anti-her 2 agent.•If there are metastases after adjuvant or 2 nd line- Taxol/ Gemzar D1 and GemzarD8 on a 3 weekly cycle.•If progression – Xeloda 900-1000mg/m2/ bd for 14 days.Other agents include Caelyx, Taxotere and Vinorelbine.

Carcinoma unknown primary:

Poorly differentiated carcinoma with mediastinal or retro peritoneal nodes esp inyoung people- could be germ cell.

Adenocarcinoma in the axilla - treat like breast.Adenocarcinoma with peritoneal disease or liver mets in female - treat likeovarian.Check CA 125.

Adenocarcinoma in males esp bone mets- could be prostate.

SCC -Nodal disease in the neck – treat like head and neck cancer. Nodes in inguinal region—could be anal or vulval primary.

Cervical cancer-

Early disease- surgery, locally advanced- chemoradiotherapy with weekly cisplatin,

Metastatic- Platinum and 5FU.

Colon cancer-

*Stage 1 and stage 2 with no risk factors- surgery alone,

*Stage 2 with adverse features - possible benefit from chemotherapy since the prognosis can be as bad as stage3.


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Adverse features- lympho vascular invasion, poorly differentiated tumours,obstruction, perforation, invasion of other organs.

5FU weekly at a dose of 500mg/m2 with leucovorin( 50 mg flat dose).CI- unstable angina.

*Stage 3 -

FOLFOX using a Port-a-cath or XELOX .In patients who cannot toleratecombination chemotherapy, Capecitabine (xeloda) is an alternative.FOLFOX more effective than Xeloda. Difference is 7% disease free survival.)

*Stage 4 ( includes rectal cancers)-

Consider resectability in selected patients: Those patients would benefit from 3cycles of Oxaliplatin based regimen prior to surgery then more chemotherapy.

Good performance, bilirubin


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GBM:Surgery is for resectable disease.For resected GBM, Temazolamide with RT and 4 weeks later, 5days per month for 6months improves survival.Temozolomide.

With RT- 75mg/m2/day M-F.After RT or on its own for palliation- 150-200 mg/m2/day for 5 days a month.

Check platelets in 2 weeks.

For recurrent Anaplastic astrocytoma- same as above.

Germ cell tumours-

Stage 1 -

Normally for stage 1 seminoma (make sure serum AFP normal)- Single dose carboAUC 7, with neulasta. Check counts every week for 2 weeks post.Remember sperm banking. or wait and watch in selected cases.

For stage 1 non seminoma - wait and watch (6 weekly markers and 3 monthly CTsfirst 2 years and later relax to 6 monthly scans and 3 monthly bloods for another 3years).or 2 cycles of BEP for patients who are not reliable or who move around.

Stage 2 onwards-This includes patients with normal scans but have the markers elevated fewweeks post orchidectomy.

Seminoma:

Stage 2 -


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Pre BEP treatment:

History of renal, auditory, neuropathy and vascular issues,Lung function test- DLCO and lung volumes,Sperm banking( Semen cryopreservation: In Townsville, this is performed by QFG),

ELFTS, FBC, LDH and markers.( Smoking to be discouraged).Recurrent GCTs can still be cured by TIP or VIP chemotherapy.

Prognostic groups:

Depend on site of primary, presence or absence of non pulmonary visceral metastasisand marker level.

Seminoma:

Good prognosis Intermediate prognosisPrimary site any any

Presence of nonpulmonary metastasis

no yes

Markers( note- not AFP) any any

If Alfa Feto Protein is elevated, it is treated as non seminoma.

Non Seminoma:

Good Intermediate PoorPrimary site Non mediastinal Non mediastinal mediastinal

Non pulmonarymetastasis

no no yes

Markers

AFP 10000B HCG 50000LDH 10 x ULN


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Head and neck-

Resectable disease- Surgery.For high risk disease, post op radiotherapy with chemotherapy improves survival.

Unresectable disease or organ preservation-

Induction chemotherapy followed by chemoradiotherapy.

Induction chemotherapy - 2 -3 cycles of TPF.Chemoradiotherapy - weekly cisplatin 40mg/m2.

*If not fit for weekly cisplatin , abnormal renal function or cardiac issues-Cetuximab (Erbitux) Loading dose 400mg/m2 one week prior to RT and then weekly250mg/m2 weekly.

they need Phenergan 12.5mg or 25mg as premed.

Metastatic H&N cancer - (Cisplatin or Carboplatin) and 5FU.

Lung cancer-

Non Small Cell Lung cancers:

*Stage 1 to 3- Surgical resection offers the best chance of cure.

For resected stage 1b, 2 or 3 -Adjuvant chemotherapy with cisplatin/ vinorelbine x 4 cycles to improve survival infit and


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.In other patients with good performance status- consider Cisplatin or Carboplatin /Gemcitabine( Day1 and Day 8).

Or Carboplatin/Taxol.

Once first line treatment fails- Permetexed (Alimta) 500mg/m2 every 3 weeks fornon-squamous histology And Docetaxel for squamous cell carcinoma.( see under mesothelioma for Alimta precaution).

Once Alimta fails or cannot tolerate chemotherapy- EGFR TKI Erlotinb (Tarceva) orIressa(Gefitinib) if there is mutation in EGFR genes..Non metastatic pan coast tumours- chemoradiotherapy followed by surgery.

Small cell lung cancer-

Limited stage -Cisplatin and etoposide x 4 cycles and radiation as early as possible or Carboplatinand etoposide for 6 cycles and radiation.At the end of the treatment, if no brain mets- Prophylactic cranial irradiation to addanother 5% survival benefit.

Extensive stage- Carboplatin and etoposide for 6 cycles. If complete response that last for 6-12 months,could have re treated.

Melanoma-

Stage 1 to 3- resection of the primary +/- sentinel node biopsy and node dissection fornode positive disease.

For stage 3 disease- adjuvant Interferoncould offer a small survival benefit . But hassignificant toxicity.Adjuvant radiotherapy.

Stage4-

Resection of solitary metastasis could offer survival benefit, even when they areon multiple organs.Unresectable disease: Enrollment in clinical trials is the best approach.Check for B-raf mutation . If B-raf mutated, consider targeted agents likevemurafenib.

Chemotherapy; In fit patients even with brain mets-Fotemustine 100mg/m2/week for 3 weeks then rescan after a 4 week break.

If response and good tolerance without too much cytopenias- 100mg/m2 every 3weeks Fotemustine.


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Mesothelioma-

Surgical decortication can be useful in selected patients.

Otherwise, Carbo AUC 5 or Cisplatin and Alimta 500mg/m2 every 3 weeks.( Important- 1 week before Alimta- start VitB12 1000mcg IM every 9 weeks and folicacid 0.5 mg daily until Alimta is stopped.

Oesophagus:

SCC:

Curable:

Surgery or Chemo radiotherapy.

Chemoradiotherapy:

Cisplatin and 5FU. ( Cis 25mg/m2 daily x4 days, and 5FU 800 mg/m2/day x 4 daysvia CADD) week 1 and week 5 of RT.

Unfit- no chemo or Carbo/5FU. Carbo AUC 5.

Surgery:

Same chemotherapy for 3 cycles then Surgery.

Incurable:

Same chemotherapy for 2-3 cycles then reassess.

Adenocarcinoma:

Curable:ECF x3 then surgery then 3xECF.Incurable:EOX or ECX or ECF.


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Ovarian cancer-( Epithelial ,not Carcino sarcoma or mixed mullerian tumour)

Stage 1 - surgery, ( chemotherapy for rupture or positive peritoneal washing)

Stage 2 onwards- debulking surgery, BSO/TAH

( In selected stage 4 this can be useful).Post debulking surgery- Carbo AUC 5 and taxol 175mg/m2 every 3 weeks.If not so fit- Carboplatin AUC 5 alone.

NB- patients who are unfit for surgery can be given chemotherapy first and havesurgery later.Intraperitoneal chemotherapy is used in selected stage3 disease, after optimumdebulking surgery.

If cancer returns 6 months after completeing Carbo or carbo/Taxol, (this constitutes platinum sensitive relapse)- try Carbo AUC 4 day 1 and Gem 1000mg/m2 day 1 andday 8.If less than 6 months ( platinum resistant relapse)- Caelyx 40mg/m2 every 4 weeks.

Pancreas-

Early disease-resection is the gold standard. Adjuvant chemotherapy with 5FU or gemcitabine

offers survival benefit.

Metastatic -weekly Gemzar 1000mg/m2 for 7 weeks and 1 week off. Then stage at the end of thisinduction. If response is confirmed, 3 weeks on 1 week off until progression or sideeffects limit.

Stomach/ adenocarcinoma of distal esophagus-

T1 and T2-Surgery alone.

T3 onwards for resectable disease:

Peri operative approach:MAGIC protocol - 3 x ECF → Surgery → 3 xECF.

Post operative approach:

Surgery → Mayo regimen 1 cycle( 5FU 425 mg/m2 and LV 50mg) → ( 4 weeks later)RT ( 5FU 400 mg/m2 and LV 50 mg- D1-D4 during week 1 and d1-3 during week 5)→ ( 4 weeks later) 2 cycles of Mayo.

Metastatic: EOX or ECX or ECF.


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Prostate-Treatment depends on disease stage and hormone sensitivity.

Early stage disease is treated with surgery, radiotherapy ( external beam and/ or brachytherapy) or observation. Treatment modality is individualised based on severalfactors: age and co morbidities of the patient, serum PSA level, Gleeson score,clinical stage and patient preference based on benefits and side effects of therapy.

For example, a patient with clinically non apparent tumour with Gleason score of


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Symptom controlDiscussion with palliative care is helpful.However, basic principles are as follow:1. Pain ----always find out the cause of the pain before prescribing analgesics

Total daily morphine requirement will guide to the required daily slowrelease dose. When prescribing breakthrough---dose is 1/6 th of the daily dose. So, ifyou are increasing the daily dose, break through need to increase as well. If oral intakeis difficult—patches or infusional morphine are options.2. Dyspnoea ---again find out the cause, for cancer related dyspnoea—morphinenebulised and anxiolytics could be helpful.

References:1. National cancer institute common toxicity criteria ( (CTCAE, version 4.03,

June 2010), National Institutes of Health, National Cancer Institute .

http://ctep.cancer.gov .

2. Hesketh, P. J. (2008). "Chemotherapy-induced nausea and vomiting." NewEngland Journal of Medicine 358 (23): 2482-2494.

3. Roila, F., J. Herrstedt, et al. (2010). "Guideline update for MASCC and ESMOin the prevention of chemotherapy- and radiotherapy-induced nausea andvomiting: results of the Perugia consensus conference." Annals of Oncology21 Suppl 5 : v232-243.

4. Freifeld, A. G., E. J. Bow, et al. (2011). "Clinical practice guideline for the useof antimicrobial agents in neutropenic patients with cancer: 2010 Update bythe Infectious Diseases Society of America." Clinical Infectious Diseases52 (4): 427-431.

5. National Comprehensive Cancer Network (NCCN) Clinical PracticeGuidelines in Oncology. Prevention and treatment of cancer-relatedinfections. Version 2.2011. www.nccn.org .

6. Therapeutic guidelines. online-tg-org-au.cknservices.dotsec.com

7. Albanell & Boselga. sem oncol 27. 3:347-361, 2000

8. www.nccn.org.

9. www.eviq.org.au.

10. Slamon, D., W. Eiermann, et al. (2011). "Adjuvant trastuzumab in HER2- positive breast cancer." New England Journal of Medicine 365 (14): 1273-1283.

Documents

Med Onc Jnr Handbook