Medical Oncology Hand book for Junior Medical Staff.

Dr Sabe Sabesan & Dr Suresh Varma, Department of Medical Oncology,

Townsville Cancer Centre.

2009.

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. Unless you are an advanced trainee in medical oncology, memorising

chemotherapy protocols would not be that useful. 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 term. 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. Medical staff Duties ------------------------------------------------------------------------5

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

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

Important practice points for common drugs-------------------------------------------10

Antiemesis ----------------------------------------------------------------------------------11

Febrile neutropenia-------------------------------------------------------------------------13

Extravasation--------------------------------------------------------------------------------15

Premedications for Taxanes --------------------------------------------------------------18

5. Medical emergencies---------------------------------------------------------------------19

6. Summary of management of common cancers:------------------------------------20

Anus-------------------------------------------------------------------------------------------20

Bladder----------------------------------------------------------------------------------------20

Breast------------------------------------------------------------------------------------------21

Carcinoma of unknown primary-----------------------------------------------------------23

Cervix------------------------------------------------------------------------------------------23

Colo rectum-----------------------------------------------------------------------------------23

GBM-------------------------------------------------------------------------------------------24

Germ cell tumours----------------------------------------------------------------------------25

Head and neck--------------------------------------------------------------------------------27

Lung cancer-----------------------------------------------------------------------------------27

Melanoma-------------------------------------------------------------------------------------28

Mesothelioma---------------------------------------------------------------------------------29

Oesophagus------------------------------------------------------------------------------------29

Ovary-------------------------------------------------------------------------------------------30

Pancreas----------------------------------------------------------------------------------------30

Prostate-----------------------------------------------------------------------------------------31

Stomach and distal oesophagus-------------------------------------------------------------30

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Senior Medical Staff:

1. Dr Sabe Sabesan,

BMBS( Flinders), FRACP, Director, Medical Oncology, Staff Specialist/Senior lecturer. Mobile: 0417 164 043.

2. Dr Suresh varma, MBBS,MD,DM, FRACP, Senior Staff Specialist. Mobile: 0447 749 370.

3. Dr Christine Mitchell, GP-SMO.

Mobile: 0429 090 975.

Weekly Timetable:

Time  Mon  Tues  Wed  Thurs  Fri 0745‐0830  GI meeting 

(0800‐0900)4   Breast1 

meeting  

Gyne onc2  ( monthly) 

 

0900‐1200  Clinics SS, SV 

Clinic SV 

Clinic CM, SV 

Clinic  SS,CM 

Clinic  SV 

           1230‐1330  Grand round    Xray  

meeting 

   

1330‐  Clinic   H&N clinic4       1400‐1500  clinic      Medonc 

tutes  

1500‐1600        Reg training   1600‐1700        Lung 

meeting4  

           

1. pathology conference room, 2. NICU conference room, 3. onc conference room, 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, 6. understanding of curative vs palliative intent therapy-

Careful when discussing prognosis.

7. familiarise with the management of common malignancies including

multidisciplinary approach.

Tasks:

1. managing inpatients – routine care, consults, share the weekend roster with haematology( it is the responsibility of the regs and RMOs to do this roster).

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

(For interns, all the procedures except IV cannulation need to be supervised by registrars or consultants especially the first one). 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 chemotherapy 2. to assess quality of life –pain, fatigue, appetite, nausea etc 3. to address new concerns 4. 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 chemotherapy

Fitness for chemotherapy depends on three factors:

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

any) • blood parameters. If cure is the aim, it is usual to accept mild-to-moderate, non-life-threatening toxicities and continue treatment without delaying or reducing the dosage to minimise side effects. However, in patients with incurable metastatic disease where quality 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 status 0 Fully active, able to carry on all pre-disease performance without

restriction 1 Restricted in strenuous physical activity but able to carry out work of

a light sedentary nature 2 Ambulatory and capable of all self-care but unable to carry out any

work activities 3 Capable of only limited self-care, confined to bed or chair more than

50% of waking hours 4 Completely disabled, cannot carry on any self-care, totally confined

to 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.

Side effects from previous cycles of chemotherapy (if any)

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 not affecting function is acceptable. However, in patients undergoing fluorouracil-based therapy, ongoing or severe diarrhoea necessitates a dose delay and dose reduction of subsequent cycles. Mid-cycle neutropenic fever usually requires dose reduction of the subsequent cycle unless the cancer is curable. If the cancer is curable or a substantial duration of remission is expected, prophylactic colony stimulating factors such as pegfilgrastim 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 of ovary is offered by some fertility groups. Women who wish to discuss this option should be referred to a fertility specialist.

• Renal function. This may affect cisplatin dosage. • Lung function. This may affect bleomycin dosage (check lung function tests

every 3 weeks). • 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 during therapy).

Additionally, it is advisable to keep a close check on central lines and previous IV cannulation sites.

Blood parameters

First, consider the haematological parameters. For most regimens, a neutrophil count >1.5 x 109/L and platelet count > 100 x 109/L are needed for safe administration of chemotherapy. Some regimens, like single agent bleomycin and vincristine, are not myelotoxic and administration is not affected by blood counts. Next, review the non-haematological parameters. For example, renal function is important for cisplatin and carboplatin and liver function for docetaxel.

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Example:

1. FBC/ ELFTs- neutrophil > 1.5 , platelets > 100 for most agents. Except monoclonal antibodies, bleomycin, vincristine. Mg levels esp for cisplatin. Action- withhold treatment until recovery, then dose delay and/or dose reduction. 2. history of febrile neutropenia or any visits to the ED in between cycles or

fevers. 3. Non-haematological toxicity:

a. diarrhoea – mainly 5FU based, Irinotecan, Oxaliplatin, Taxotere action- low threshold for withholding therapy if diarrhoea the day before or moderate diarrhoea for longer than expected duration or nocturnal diarrhoea. b. mucositis/mouth care c. Emesis Action-( see antiemetics) change class, add another agent or dose reduction. d. Rashes e. neuropathy- Cisplatin, Oxaliplatin, Taxanes, Vincas dose 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 esp if they are renally cleared. Carboplatin- dose adjusted based on creatinine. h. pulmonary toxixcity- bleomycin, methotrexate

4. physical exam- esp mouth, central lines.

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When to stop cancer treatment A 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 necessitate cessation of treatment (eg. moderate to severe peripheral neuropathy with taxanes and oxaliplatin, severe enteritis from fluorouracil). Alternative regimens are sometimes available. If the cancer is incurable and the toxicities severely interfere with the activities of daily living, treatment may have to be stopped. Deteriorating performance status and organ function usually require cessation of treatment. Ongoing neutropenia or thrombocytopenia typically means the patient is not going to handle further chemotherapy. If the cancer is not responding to the therapy after 2–3 cycles, cessation of the same therapy is advised.

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

If diarrhoea daily, consider dose reduction. 5FU could also cause coronary

spasm.

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 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.

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

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Antiemesis: Causes of nausea and vomiting in patients receiving chemotherapy:

1. Chemotherapy related 2. Other causes

Chemotherapy related emesis:

1. types of chemotherapeutic agents, dosage, schedule and route of administration

2. Patient factors- past history, anxiety/ anticipation etc Emetogenic potential: High (>90%) Moderate (60-90% Moderate(30-60%) Low(10-30%) Minimal Cisplatin >50mg/m2 Carboplatin Cyclophos

<750mg/m2 Xeloda/5FU Bleomycin

Dacarbazine

Cisplatin<50mg/m2 Docetaxel Herceptin

Cyclophos>1.5g/m2 Doxorubicin>60mg/m2 Doxorubicin 20-60mg/m2

Caelyx Rituximab

Epirubicin>90mg/m2 Epirubicin <90mg/m2

Taxol Vincristine

Irinotecan,Oxaliplatin Gemzar, Temazolamide

Vinorelbine

*Acute or early nausea and vomiting- within 24 hours of chemotherapy. *delayed/late – after 24 hours of chemotherapy. Common agents include Cisplatin, Carboplatin, Cyclophosphamide and Doxorubicin. For Cisplatin, emesis reaches its maximal intensity 48-72 hours after chemotherapy and can last upto 6-7 days. *Anticipatory nausea and vomiting- Nausea before chemotherapy Antiemetics:

1. Neurokinin 1 receptor antagonist- 2. 5HT3 antagonists 3. Dopamine antagonists 4. Steroids 5. Anti histamines 6. Lorazepam-good for anticipatory emesis

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High emetogenic drugs and anthracycline containing regimens for breast cancer:

Emend (Aprepitant)- Day 1- 1 hour pre chemo 125 mg orally, day 2 and 3- 80 mg daily. Plus Zofran ( Ondansetron) 8mg bd for 2-3 days starting the night of chemotherapy. Plus Dexamethasone- 4mg bd for 2-3 days( normally mane and 2pm to reduce insomnia) NB- for patients who experience sudden decline in well being when steroids are stopped, a weaning off regimen might be useful. Maxolon- 10 mg Q6H PRN. NB- Zofran can be constipating- so warn pts about prevention of constipation.

Moderately emetogenic drugs or combination of drugs:

Zofran ( Ondansetron) 8mg bd for 2-3 days starting the night of chemotherapy. Plus Dexamethasone- 4mg bd for 2-3 days( normally mane and 2pm to reduce insomnia) NB- for patients who experience sudden decline in well being when steroids are stopped, a weaning off regimen might be useful. Maxolon- 10 mg Q6H PRN. NB- Zofran can be constipating- so warn pts about prevention of constipation.

Mildly emetogenic drugs: Usually maxolon premedication with maxolon 10 mg Q6H PRN would be enough. If nausea not controlled with maxolon, might have to treat it like moderate drugs after excluding 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

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INFECTIONS

Neutropenic Fever It is a medical emergency. It is the responsibility of the MO ensure prompt antibiotic administration. With diarrhoea and neutropenia, even if afebrile, use the same protocol. Definitions • A single oral temperature of 38.30 • A temperature ≥ 380 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 (Hughes WT.2002 Infectious Diseases Society of America Guidelines, Clin Inf Dis 34:730-

751, 2002). Treatment of Neutropenic Fever Antibiotics • Cefepime* IV 2 g BD or Timentin 3.1 g QID + Gentamicin 5-7 mg/kg/IV ( depend on creatinine)daily with levels or Tazocin and Gentamycin. Modifications • Add Vancomycin 1 g 12 hourly if clinically unstable, gram positive blood cultures before

antibiotics, severe mucositis present, already on Quinolone prophylaxis, a catheter associated cellulitis or tunnel infection, high prevalence of Methicillin-resistant staph aureus

• Persistent neutropenic fever on D5 – add antifungal therapy (Amphotericin B 0.5mg/kg/day or Fluconazole 400mg/day)

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) consider early discharge on Day 4 on oral Ciprofloxacin 750mg BD for 5 days or cease antibiotics altogether when ANC >500/µL

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

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Guide to Febrile Neutropenia

Temperature > 38.30 x 2 over 1 hour + Neutrophil count < 500µL

Broad spectrum antibiotics

[Cefepime 2 g BD*] or anti pseudomonal penicillin + Gentamicin)

Re-evaluate on Day 3

Organism Identified Organism not identified Febrile Afebrile Adjust antibiotics to organism sensitivities

but maintain broad spectrum cover until Continue antibiotics for

neutropenic recovery 5 days or until

neutrophils > 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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EXTRAVASATION OF CHEMOTHERPAY DRUGS (Albanell & Boselga. Sem Oncol 27.3:347-361, 2000.) 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.

Cytotoxic Agents Reported to Cause Tissue Necrosis after Extravasation in at Least One Clinical Case or

Experimentally

Aclacinomycin Liposomal anthracyclines

Amsacrine* Idarubicin*

Bisantrene* Mechlorethamine*

Cisplatin Menogaril

Dacarbazine Mitomycin*

Dactinomycin Mitoxantrone

Daunorubicin* Paclitaxel

Doxorubicin* Teniposide

Epirubicin* Vinblastine*

Esorubicin Vincristine*

Etoposide Vindesine*

Fluorouracil Vinorelbine*

_____________________________________________________________________________________________

*Drugs with the highest potential of localized tissue damage after extravasation

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Guidelines for Administration of Vesicant Drugs • To ensure patency of a peripheral line, it is best to administer a vesicant drug through a

recently started line. Avoid sites in the dorsum of the hand or near joints, where

extravasation could lead to more severe functional damage.

• Whenever possible, administer vesicant agents through a central line. This is

particularly important if the agent will be administered as a continuous infusion.

• Avoid limbs with impaired circulation, such as on the side of lymph node dissection.

• Place a suitable intravenous line of compatible fluids through a 22G plastic cannula,

securely taped in place (without covering the entry site) to allow visualization.

• Never test the line with the cytotoxic drug. Observe the site for swelling and pain, and

check patency by gently drawing back blood before starting to administer the cytotoxic

drug through a three-way tap with fast flowing normal saline.

• Ask the patient to promptly report any sensation of pain or burning. In case of doubt,

stop the infusion and consider changing the site.

• Check frequently for venous blood return (every 2-3 mls) and for signs of redness and

swelling during the administration.

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Antidotes for Vesicant and Irritant Drugs Table 3

Chemotherapy agent Pharmacologic

antidote

Nonpharmacologic

Antidote

Method of

Administration

• Mechlorethamine

(nitrogen mustard)

• Cisplatin (large

extravasation)

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.

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Paclitaxel 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 given alone (4mg IV) or in combination

with other drugs.

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

no hypersensitivity reaction occurred with 1st 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.)

Monoclonal Antibodies

• Trastuzumab (Herceptin) may cause fever and chills, chest tightness and tachycardia with 1st 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.

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Medical Emergencies: requires urgent medical attention. Eg-Cord compression, SVC obstruction, Neutropenic fever, Tumour lysis syndrome. 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 referral 3. high dose steroids.

Notes:

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Summary of management of common cancers: This section outlines the principles behind the management of common cancers. Unless otherwise indicated, the information in this section is drawn from the NCCN Clinical Practice Guidelines in Oncology1 and the Cancer Institute NSW

Standard Cancer Treatment protocols program (CI-SCaT)2. Anal cancer- Most cancers are treated with chemoradiation. *For chemo radiation- mitomycin and 5FU. Contraindication- ischaemic heart disease, severe diarhhoea. *Metastasis- same regimen. Bladder- Non-muscle invasive disease is treated with surgery and adjuvant intravesical therapies (eg. intravesical therapy with BCG). Muscle invasive disease is treated with surgery. 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 care alone. 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 receptor status, 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 risk size <2cm age >35y nodes nil positive grade Grade 1 ER/PR positive Her2 negative LVI absent Low risk- hormonal manipulation or nil. Average- hormonal +/- chemotherapy for ER/PR positive disease, Chemotherapy for ER/PR negative disease. High risk- chemotherapy + hormonal manipulation for ER positive disease, Chemotherapy for ER/PR negative disease. For Her 2 positive disease, Herceptin is given with chemotherapy for total of 52 weeks ( weekly or 3 weekly). Hormonal manipulation- In premenopausal women, Tamoxifen or Zoladex + AIs. In post menopausal women- Tamoxifen or AIs. AIs are superior to Tamoxifen in terms of disease free survival. For patients on AIs- twice yearly Zometa decreases the rate of decline in bone density. Usually DEXA scans are done yearly.

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Chemotherapy regimens- Lower risk average risk- 4xAC or Taxotere/Cyclo(if cardiac issues), Higher risk average 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 cardiac toxicity. Neulasta- for adjuvant breast cancer if cycles delayed because of neutropenia or had neutropenic fever. PACS 01 and TAC needs Neulasta day2 regardless of neutropenia.All breast cancer adjuvant regimens need Emend as well as 5HT3 antagonist and dexamethasone for antiemetic prophylaxis. 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. Metastatic breast cancer- • ER/PR positive bone only mets- hormones +/- Herceptin. •Bone mets also benefit from monthly Bisphosphonates to reduce pain, skeletal events and hypercalcemia. •First line chemotherapy is usually anthracyclines usually as single agent or with cyclo. If the disease is aggressive and of high volume that threatens survival, could offer triple agent combination like TAC. •In Her 2 positive disease, Taxanes can be combined with Herceptin as initial treatment. •If there are mets after adjuvant or 2 nd line- Taxol/ Gemzar D1 and Gemzar D8 on a 3 weekly cycle. •If progression – Xeloda 900-1000mg/m2/ bd for 14 days. Other agents include Caelyx, Taxotere and Vinorelbine.

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Carcinoma unknown primary: Poorly differentiated carcinoma with mediastinal or retro peritoneal nodes esp in young people- could be germ cell. Adenocarcinoma in the axilla- treat like breast. Adenocarcinoma with peritoneal disease or liver mets in female- treat like ovarian. 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. 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 Xeloda. FOLFOX more effective than Xeloda. Difference is 7% disease free survival. (Avastin is not beneficial) *Stage 4 ( includes rectal cancers)- Consider resectability in selected patients: Those patients would benefit from 3 cycles of Oxaliplatin based regimen prior to surgery then more chemotherapy.

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Good performance, bilirubin <25 with liver mets or normal without liver mets, no cardiac failure or active ischaemia : XELOX or XELIRI. Or FOLFOX with Avastin. (Avastin-5 mg/kg 2 weekly or 7.5mg/kg 3 weekly) For patients not keen or unfit for FOLFOX - Xeloda. When assessing for response, identify patients who could benefit from surgery. Discuss palliative care alone as an option in patients not fit for chemotherapy. After the failure of Xelox, could start Irinotecan (bilirubin must be normal) or palliative care. Rectal cancers: Same as colon cancers. Except- Stage 2 onwards- chemo radiotherapy is part of the adjuvant therapy. During radiation, 5FU is infused continuously via PICC line. For stage 3- FOLFOX is not currently proven. Stage 4- same as colon. Recurrent disease locally- depend on previous treatment. GBM: Surgery is for resectable disease. For resected GBM, Temazolamide with RT and 4 weeks later, 5days per month for 6 months 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.

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Germ cell tumours- Stage 1- Normally for stage 1 seminoma(make sure AFP normal)- Single dose carbo AUC 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 CTs first 2 years and later relax to 6 monthly scans and 3 monthly bloods for another 3 years). 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 few weeks post orchidectomy. Seminoma: Stage 2 - <5cm Radiotherapy or 3 xBEP. Stage 2 bulky or 3: Good prognosis- 3x BEP, Intermediate prognosis- 4x BEP ( only first 3 cycles are with Bleomycin). Non seminoma- Good prognosis- 3 x BEP, Intermediate or poor prognosis- 4x BEP. Residual disease after optimal chemotherapy needs to be resected. Pre BEP treatment: History of renal, auditory, neuropathy and vascular issues, Lung function test- DLCO and lung volumes, Sperm banking, ELFTS, FBC, LDH and markers. ( Smoking to be discouraged). Recurrent GCTs can still be cured by TIP or VIP chemotherapy.

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Prognostic groups: Depend on site of primary, presence or absence of non pulmonary visceral metastasis and marker level. Seminoma: Good prognosis Intermediate prognosis Primary site

any any

Presence of non pulmonary mets

no yes

Markers( note- not AFP)

any any

If AFP is elevated, it is treated as non seminoma. Non Seminoma: Good Intermediate Poor Primary site

Non mediastinal Non mediastinal mediastinal

Non pulmonary mets

no

no

yes

Markers

AFP <1000 1000-10000 >10000 B HCG <5000 5000-50000 >50000 LDH <1.5 x ULN 1.5-10 x ULN >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 cycles of TCF. Chemoradiotherapy- weekly cisplatin 40mg/m2. *If not fit for weekly cisplatin, abnormal renal function or cardiac issues- Erbitux. Loading dose 400mg/m2 one week prior to RT and then weekly 250mg/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- Surgery offers the best chance of cure. For resected stage 2 or 3 lung cancers- Carbo/Taxol x 6 to improve survival in fit and <70 years. *Stage 3- For patients who are unresectable, chemoradiation can improve survival. concurrent with radiation- in fit patients— Carbo(AUC 2) and Taxol(50mg.m2) weekly with radiation. NB- in selected patients with low volume N2 disease, induction chemotherapy followed by surgery may be considered.

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*Stage 4 or incurable stage 3- Palliative care is a good option for borderline patients. If brain mets-no chemo until brain mets are stable for 3 months . If no brain mets and fit - consider Cisplatin or Carboplatin /Gemcitabine( Day1 and Day 8). Or Carboplatin/Taxol. Once first line treatment fails- Alimta 500mg/m2 every 3 weeks if they are fit. ( see under mesothelioma for Alimta precaution). Once Alimta fails or not so fit but still walking around- Tarceva on authority. 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 Carboplatin and etoposide for 6 cycles and radiation. At the end of the treatment, if no brain mets- Prophylactic cranial irradiation to add another 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 for node positive disease. For stage 3 disease- adjuvant IFN could offer a small survival benefit. Stage4- Resection of solitary metastasis could offer survival benefit, even when they are on multiple organs. Unresectable disease- 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 3 weeks 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 folic acid 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 days via 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 on LIDS.

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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 have surgery later. 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 and day 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 this induction. If response is confirmed, 3 weeks on 1 week off until progression or side effects 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 on LIDS

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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 several factors: 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 <6 who has a life expectancy of <10 years could be actively observed without any impact on survival. For locally advanced inoperable disease, radical radiotherapy could lead to cure. Androgen deprivation therapy is sometimes used for short periods( 4-6 months) before/concomitantly/ after radiotherapy in selected high risk patients. Metastatic disease is incurable and the aims are to prolong survival and improve quality of life. Hormone Sensitive disease:

• Hormone sensitive tumours are treated with a GnRH agonist (eg- goserelin,leuprorelin). To prevent flare, antiandrogens(eg- flutamide, cyproterone) are started 2-3 weeks before the injection and continued for another 3-4 weeks. Whether anti androgens are continued beyond that is controversial.

Hormone Refractory disease:

• Hormone refractory disease includes patients where the disease has progressed despite hormonal manipulation. GnRH agonists are usually continued. Chemotherapy improves median survival by up to 3 months and maintains improvement in quality of life.

• Bone metastases are treated with intravenous bisphosphonates (eg-zoledronic acid) monthly. For asymptomatic disease, chemotherapy is usually delayed. • Symptomatic metastases or rapid rise in PSA (doubling time of <3 months) may

be treated with docetaxel and prednisone- Taxotere 75mg/m2 and prednisone 5mg bd from day 1- duration of chemo -(. Palliative care is another option.

• Localised bone pain responds to external beam radiotherapy very well. Men with multifocal painful bone metastases and those with persistent or recurrent pain despite receiving EBRT to maximal normal tissue tolerance may achieve palliation of their symptoms by treatment with bone-targeted radioisotopes such as strontium-89.

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References: 1.http://www.nccn.org/professionals/physician_gls/f_guidelines.asp?button=I+Agree 2. https://www.treatment.cancerinstitute.org.au/cancerinstitute.

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