protokol kemoterapi

THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST

Issue Date: 30th October 2012 Page 1 of 148 Filename: MCHACPROTO Issue No: 10.0

Author: Dr. D.B. Smith Authorised by: Dr. D.B. Smith Copy No:

CHEMOTHERAPY PROTOCOLS

V10.0




CCC Chemotherapy Protocols 2012 General observations .................................................................................................................................5

Protocol Additions 2012.............................................................................................................................5

Cancer Drugs Fund ...................................................................................................................................5

Off Protocol Treatment Policy ...................................................................................................................5

Trials ..........................................................................................................................................................5

Co-payments / top-ups / additional private care........................................................................................5

Dose Capping............................................................................................................................................6

Breast Cancer..............................................................................................................................................7

Adjuvant.....................................................................................................................................................7

Neo-adjuvant ...........................................................................................................................................11

Advanced disease ...................................................................................................................................12

Patients with compromised liver or marrow function...............................................................................16

Bone directed therapy .............................................................................................................................18

Management of patients with HER2 positive cancers.............................................................................19

Gastrointestinal Cancer............................................................................................................................21

Oesophageal Carcinoma.........................................................................................................................21

Adjuvant ...............................................................................................................................................21

Neoadjuvant.........................................................................................................................................21

Gastric / Adenocarcinomas of Gastro-oesophageal junction Carcinoma ...............................................24

Neoadjuvant / Adjuvant........................................................................................................................24

Adjuvant ...............................................................................................................................................24

Pancreatic cancer....................................................................................................................................28

Adjuvant ...............................................................................................................................................28

Cholangiocarcinoma / Gall Bladder Carcinoma ......................................................................................31

Advanced .............................................................................................................................................31

Hepatocellular carcinoma* ......................................................................................................................33

Neuroendocrine tumours.........................................................................................................................34

Colorectal ................................................................................................................................................36

Adjuvant ...............................................................................................................................................36

Rectal cancer - Chemoradiation..............................................................................................................38

Advanced Colorectal Cancer...................................................................................................................39

Anal Carcinoma.......................................................................................................................................47

Gynaecological Cancer ............................................................................................................................49

Epithelial Ovarian Cancer........................................................................................................................49

Epithelial Ovarian Cancer Mucinous Histology ....................................................................................56

Endometrial Carcinoma...........................................................................................................................58

Cervical Cancer .......................................................................................................................................60

Adjuvant ...............................................................................................................................................60

Haematological Malignancies..................................................................................................................65

rOFI y sAUNARHighlight







Hodgkins disease ....................................................................................................................................65

Non-Hodgkins Lymphoma.......................................................................................................................67

Head and Neck Cancer .............................................................................................................................72

Nasopharyngeal Carcinoma....................................................................................................................75

Thyroid Cancer ........................................................................................................................................76

Lung Cancer ..............................................................................................................................................77

Small Cell ................................................................................................................................................77

Non-Small Cell Lung Cancer...................................................................................................................80

Mesothelioma ............................................................................................................................................87

Melanoma...................................................................................................................................................88

Sarcomas ...................................................................................................................................................89

Soft Tissue Sarcoma ...............................................................................................................................89

Adjuvant ...............................................................................................................................................89

Neo-adjuvant........................................................................................................................................89

Osteosarcoma / MFH of bone / Leiomyosarcoma of Bone .....................................................................91

Advanced Osteosarcoma ........................................................................................................................93

Ewings Sarcoma......................................................................................................................................94

Neoadjuvant.........................................................................................................................................94

Aggressive fibromatosis ..........................................................................................................................99

Rhabdomyosarcoma ...............................................................................................................................99

IVADo Regime for High Risk Rhabdomyosarcoma...............................................................................101

Gastro-intestinal Stromal Tumours (GIST)............................................................................................103

Urological Cancer ...................................................................................................................................104

Bladder Cancer - Transitional cell .........................................................................................................104

Renal cancer .........................................................................................................................................108

Prostate Cancer.....................................................................................................................................111

Germ Cell Tumours ...............................................................................................................................113

Adjuvant .............................................................................................................................................113

Primary CNS Malignancy .......................................................................................................................117

Adjuvant Temozolomide ....................................................................................................................117

Primary CNS Lymphoma........................................................................................................................121

Adenocarcinoma of Unknown Primary Origin .....................................................................................124

CCC Emergency Chemotherapy Drugs ................................................................................................125

Bone Metastases.....................................................................................................................................126

CCC anti-emetic guidelines for cytotoxic chemotherapy ...................................................................127

GCSF ........................................................................................................................................................130

Primary Prophylaxis...............................................................................................................................130

Secondary Prophylaxis..........................................................................................................................130

Erythropoietin..........................................................................................................................................132

Intrathecal (IT) Chemotherapy ...............................................................................................................133

Creatinine Clearance ..............................................................................................................................134











Calvert formula for Carboplatin dosage ...............................................................................................134

Cisplatin dose guidelines.......................................................................................................................134

Cisplatin Hydration Policy......................................................................................................................135

Haematological Indices Guidelines for the administration of chemotherapy ...............................136

Capecitabine-...........................................................................................................................................136

Renal function recommendations .........................................................................................................136

Neutropenic Sepsis Policy.....................................................................................................................137

Platelet Transfusion Policy ....................................................................................................................138

Hypocalcaemia ........................................................................................................................................138

Hypomagnesaemia .................................................................................................................................138

Ifosfamide Encephalopathy and Methylene Blue ................................................................................139

Ifosfamide Renal Toxicity.......................................................................................................................139

Folinic acid rescue for High Dose Methotrexate .................................................................................140

CCC Dose Banding Policy......................................................................................................................140

Surface Area Nomogram........................................................................................................................148








General observations

There is now an electronic version of the protocol book which is available on CCO Comms and the CCC

internet site. This will be updated as required during the year and represents the working version of the

book. The paper version will continue but will only be updated annually.

Protocol Additions 2012

Maintenance pemetrexed in advanced NSCLC

Pazopanib in advanced renal cell carcinoma

Gefitinib in advanced NSCLC

In addition we have included all drugs currently funded by the Cancer Drugs Fund. Please refer to the

NW Cancer Drugs Fund website for the latest funding policy and conditions for approval. Please note

that there may be a 90 day period before a NICE approved drug is funded routinely and therefore

doesnt need a CDF application.;

Cancer Drugs Fund

A number of treatments are now available via the Cancer Drugs Fund. The process for accessing

the fund is as follows:

Complete the relevant application form which can be found on the North West Cancer Drugs

Fund web site. The easiest way to find this is to type nw cancer drugs fund into google and

select the application forms button in the header on the home page.

E-mail the completed form to the pharmacy dept at CCC using:

[email protected] this address can be found by typing cco pharmacists into the

address book in outlook.

Off Protocol Treatment Policy

Inevitably situations will arise that are not covered by the standard CCC protocols. Consultants who wish

to use a non-protocol regimen should complete the non-protocol treatment form and submit it to the

Clinical Director for Chemotherapy for approval at least 5 days prior to the date of cycle 1 of the proposed

treatment. All reasonable requests will be granted.

Trials

Entry to clinical trials should be considered for all patients but individual studies have not been listed due

to frequent changes.

Co-payments / top-ups / additional private care

The uptake of co-payments has been minimal and has been further reduced by the introduction of the

Cancer Drugs Fund. However the process is still in place and is outlined below.




Co-payment refers to top-up funding by an NHS patient for an otherwise unavailable treatment. NHS

policy allows patients to fund elements of their care not currently available on the NHS without losing their

entitlement to continue with free NHS care.

The CCC co-payments policy considers access to systemic cancer treatments - chemotherapy or

targeted therapies - that are currently not funded for use in NHS patients. A copy of the policy can be

obtained from pharmacy or found on the CCC website and includes all the required documentation:

Co-payment algorithm

Additional Private Treatment Form

Patient information leaflet.

Financial agreement forms.

The self-funded drug may be a single agent or given in combination with standard treatments, in which

case the costs incurred relate only to the self-funded drug. However it should always be clear which

components of treatment are privately funded and which are provided as NHS treatments.

The patient commits to self-funding the treatment for the duration of the entire programme under

supervision by the responsible consultant i.e. a specific number of cycles or indefinite period while there

is evidence of a maintained benefit and response. This will include the costs of treatment preparation and

delivery, payment of any investigations needed, and any supportive care drugs given as a direct

consequence of receiving the self-funded treatment.

Dose Capping

In line with ASCO guidelines we have removed routine dose capping for patients with a surface area in

excess of 2m2.




Breast Cancer

Adjuvant

Epi-CMF

Epirubicin 100mg/m2 IV day 1 repeated at 21 day intervals x 4 cycles

followed by CMF x 4 cycles

Laboratory Investigations

Ensure normal renal and hepatic function prior to cycle 1 and repeat during

subsequent cycles if clinically indicated

Where renal / hepatic function are abnormal treatment is at physician discretion

LV ejection fraction prior to cycle 1 if history of cardiac problems

FBC prior to each cycle.

CMF Cyclophosphamide 100mg/m2 po days 1-14 in divided doses

Methotrexate 40mg/m2 IV days 1 and 8

Fluorouracil 600mg/m2 IV days 1 and 8

For patients unable to tolerate oral cyclophosphamide substitute

IV cyclophosphamide 600mg/m2 days 1 and 8

Folinic acid rescue not normally required unless patients develop signs of Methotrexate

toxicity, then 15mg 6 hourly x 6 doses starting 24hrs post Methotrexate with subsequent

cycles

Cycles are repeated at 28 days from day 1 to a total of 6 cycles.




Where renal / hepatic function are abnormal treatment is at physician discretion but

Methotrexate is hazardous in the presence of renal insufficiency

FBC prior to each cycle, not required on day 8

Standard FBC limits for administration apply

AC Doxorubicin 60mg/m2 + cyclophosphamide 600mg/m

2 IV day 1 repeated at 21 day

intervals for 4 cycles has been shown to be equivalent to 6 cycles of CMF.









FBC prior to each cycle


EC Epirubicin 90mg/m2 IV + cyclophosphamide 600mg/m

2 IV day 1 repeated at 21 day intervals for 4

cycles. Alternative to AC in this situation








FEC / Docetaxel

This protocol is available for node positive or high risk node negative patients.

Patients should receive primary prophylaxis with pegfilgrastim after each cycle

FEC Fluorouracil 500mg/m2 IV day 1

Epirubicin 100mg/m2 IV day 1

Cyclophosphamide 500mg/m2 IV day 1

Repeat at 21 day intervals for 3 cycles








Followed by




Docetaxel 100 mg/m2 IV x 3 cycles at 21 day intervals

Pre-medication: Dexamethasone 8mg oral bd x 3 days start 24hrs pre-docetaxel







NB: See section on advanced disease for dose modifications and precautions.

Trastuzumab For patients with HER2 positive cancers

Non-metastatic potentially operable primary invasive breast cancer

HER2 positive (IHC 3+ and / or FISH positive)

Completed definitive surgery and radiotherapy

Completed at least 4 cycles of adjuvant or neoadjuvant chemotherapy

Within 9 weeks of chemotherapy / radiotherapy / surgery, whichever is

last.

ECOG PS 0 or 1

Baseline LVEF normal after completing anthracycline chemotherapy

No serious cardiac illness

Trastuzumab 8mg/kg IV loading dose over 90min then 6mg/kg over 60min and

thereafter over 30 min every 3 weeks for 12 months (18 cycles) if no

problems.

May be given concurrently with docetaxel.

Stop at any time if CCF develops

LVEF at 3, 6, 9 and 12 months

Stop trastuzumab if LVEF falls by 10 points or to




In patients at significant risk of cardiac problems:

HER2 negative

TC Docetaxel 75mg/m2 IV

Cyclophosphamide 600mg/m2 IV

Repeat at 21 day intervals for 4-6 cycles








HER2 positive

TCH Docetaxel 75mg/m2 IV

Carboplatin AUC6

Trastuzumab 8mg/kg iv loading dose over 90min then 6mg/kg over

60min and thereafter over 30 min every 3 weeks for 12 months (18

cycles) if no problems commencing with first cycle of

chemotherapy











Neo-adjuvant

Indication / Treatment plan

Patients with locally advanced disease or to allow less radical surgery in patients with

operable tumours.

Options include six cycles of EC/AC or four cycles EC/AC followed by four cycles

docetaxel at 100mg/m2

HER-2 positive patients may commence trastuzumab following completion of

anthracycline based treatment i.e. concurrently with docetaxel if this is being given

provided LVEF normal after completion of the anthracycline. Patients should then have

the remaining 14 cycles of trastuzumab as adjuvant treatment.

Patients should receive primary prophylaxis with pegfilgrastim after each cycle

AC/EC Doxorubicin 60mg/m2

IV day 1

or


+


Repeat at 21 day intervals for up to 6 cycles.








Docetaxel 100 mg/m2 IV q 21 days x 4 cycles











NB: See section on advanced disease for dose modifications and precautions.

Advanced disease

First line

Doxorubicin 75mg/m2 IV day 1

Repeat at 21 day intervals usually to a maximum of 6 cycles

AC/EC Doxorubicin 50mg/m2 IV day 1

or

Epirubicin 90mg/m2 IV day1


Repeat at 21 day intervals usually to a maximum of 6 cycles







Normal FBC limits for administration apply




Docetaxel 75-100 mg/m2 IV day 1 q 21 days, max 6 cycles


Criteria

Previously received full dose anthracycline as adjuvant therapy

or

Less than six months since anthracycline based adjuvant therapy

or

Unsuitable for anthracycline therapy

NB: See section on 2nd/3

rd line treatment for dose modifications and precautions.







Docetaxel / Capecitabine

Docetaxel 75mg/m2 IV day 1

+

Capecitabine 1000mg/m2 bd oral days 1-14

NB see capecitabine renal function recommendations p130

Pre-medication Dexamethasone 8mg bd x 3 days start 24hrs pre-docetaxel

Repeat at 21 day intervals, max 6 cycles

Criteria

PS 0-1 NB very fit patients only

Recurrent following adjuvant anthracycline therapy










Paclitaxel / Gemcitabine

Paclitaxel 175mg/m2 IV day 1

Gemcitabine 1250mg/m2 IV days 1 and 8

Pre-medication Chlorphenamine 10mg

Dexamethasone 16mg

Ranitidine 50mg

Repeat at 21 day intervals, max 6 cycles

Criteria

PS 0-1 NB very fit patients only

Recurrent following adjuvant anthracycline therapy







*Bevacizumab 10mg/kg IV infusion

Repeat at 14 day intervals

Criteria Advanced disease

Triple negative

First line chemotherapy

In combination with paclitaxel

*NB available via the Cancer Drugs fund




*Eribulin 1.23mg/m2 eribulin mesylate IV days 1 and 8 of a 21 day cycle

Criteria At least 2 prior chemotherapy regimens for advanced disease

Evidence of response to prior chemotherapy


Everolimus + exemestane

Everolimus 10mg oral daily

Exemestane 25mg oral daily

Continue until progression / unacceptable toxicity

Criteria progression on non-steroidal aromatase inhibitor





Patients with compromised liver or marrow function

Doxorubicin 20mg/m2 IV weekly for patients with compromised liver or marrow function due to

tumour infiltration


Ensure normal renal function prior to cycle 1 and repeat during subsequent cycles if

clinically indicated

Patients with abnormal hepatic function should be treated cautiously




Normal limits for administration apply with the exception that for patients with marrow

infiltration treatment may be continued at lower platelet and neutrophil counts at

treating physician discretion.

Continue with weekly treatment usually for 6-8 weeks before changing to fortnightly or 21

day cycles depending on response. Maximum total dose 450mg/m2

Paclitaxel 80mg/m2 IV weekly for patients with compromised liver or marrow function who have

previously received anthracyclines.

Pre-medication

Dexamethasone 8mg IV before first cycle

4mg IV before second and subsequent cycles

Chlorphenamine 10mg IV

Ranitidine 50mg IV

Laboratory investigations

Ensure normal renal function prior to cycle 1 and repeat during subsequent cycles if


Patients with abnormal hepatic function should be treated cautiously



Normal limits for administration apply with the exception that for patients with marrow

infiltration treatment may be continued at lower platelet and neutrophil counts at

treating physician discretion.




Vinorelbine 25 - 30mg/m2 IV day 1 and 8 of a 21 day cycle.

or

60- 80mg/m2 oral day 1 and 8 of a 21 day cycle

Repeat at 21 days from day 1

Reassess after every 2 cycles, maximum 6 cycles

Criteria: WHO performance status 0-1

Endocrine resistant

Prior alkylating agent therapy







Capecitabine 1000-1250mg/m2 oral twice daily for 14 days followed by 7 days off

Or

850-1000mg/m2 twice daily for 14 days followed by 7 days off

if heavily pre-treated or elderly


Repeat at 21 days from day 1 for up to six cycles.

Criteria Failed or unsuitable for anthracycline and/or taxane

PS 0-2










Bone directed therapy

Bisphosphonate

Zoledronic acid 4mg IV in 100mls Sodium chloride 0.9% over 15-30 minutes repeated at 28

day intervals.

Criteria: Performance status 0-2

Symptomatic / extensive bone metastases

Calcium supplements:

Patients should have their serum calcium measured every four weeks

and Adcal D3 tablets prescribed as necessary.

Renal impairment

Cr clearance Dose

>60 4.0mg

50 - 60 3.5mg

40 - 49 3.3mg

30 39 3.0mg

< 30 no treatment

Serum creatinine should be repeated every 4 weeks and if it rises significantly

during treatment zoledronic acid should be witheld until the creatinine has

returned to within 10% of the baseline prior to starting.

For patients with creatinine clearance < 30ml/min ibandronic acid 50mg weekly

oral may be considered.

*This is available via the off-protocol mechanism

*Denosumab 120mg sc monthly

Criteria Patients ineligible for IV bisphosphonate due to poor venous

access or renal impairment





Management of patients with HER2 positive cancers

Trastuzumab 4 mg/kg loading dose IV. over 90 minutes followed by 2mg/kg/week IV over 30

minutes for 8 doses then 6mg/kg every 3 weeks over 30minutes.

or

8mg/kg IV loading dose over 90min then 6mg/kg over 60min for one dose and

then over 30 min thereafter if no problems every 3 weeks

Criteria: Strongly HER2 positive (HER2 3+ by IHC or FISH positive)

Trastuzumab given together with a taxane or vinorelbine as first or

second line treatment or second / third line as a single agent.

NB not with anthracycline and with care within close proximity to

anthracycline therapy (< 6 months).

LVEF: baseline ECHO/MUGA + 3 monthly repeat advised for patients

receiving treatment with trastuzumab.

*Lapatinib (Tyverb) + capecitabine

Lapatinib 1250mg po daily continuously

+

Capecitabine 1000mg/m2 oral twice daily for 14 days followed by 7 days off

or

850mg/m2 twice daily for 14 days followed by 7 days offif heavily pre-treated or elderly


Repeat at 21 days until progression or toxicity. For some responding patients continuing

with lapatinib alone may be the right approach if capecitabine toxicity becomes

unacceptable.

Criteria Prior anthracycline, taxane and trastuzumab

PS 0-2

IHC 3+ or FISH positive cancer










*Available via the Cancer Drug Fund

*Paclitaxel Albumin (Abraxane)

260mg/m2 IV repeat at 21 day intervals

Consider if no longer safe to continue with paclitaxel or docetaxel. Patients may be able

to receive Abraxane with premedication and appropriate precautions.

Criteria Metastatic breast cancer

Situations where taxanes are indicated







*Available via the Cancer Drugs Fund




Gastrointestinal Cancer

Oesophageal Carcinoma

Adjuvant

Not currently recommended as standard therapy

Neoadjuvant

Cisplatin/5FU Cisplatin 80mg/m2 IV day 1

Fluorouracil 1g/m2 over 24hrs IV days 1-4

or

Capecitabine 1000mg/m2 bd x 14 days

Repeat at 21 days for two cycles.

Criteria PS 0-1

Cr Cl > 50ml/min

Operable oesophageal cancer


Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if


Calculate creatinine clearance prior to each cycle and administer cisplatin according to

guidelines




Locally advanced

Chemo-radiation protocol

Cisplatin/5FU Cisplatin 80mg/m2 IV day 1 and 29

Fluorouracil 1g/m2 IV over 24hrs days 1-4 and 29-32

or

Capecitabine 825mg/m2 oral bd Mon-Fri during XRT

+ XRT

followed by two additional cycles after completion of XRT








guidelines




Cisplat/Capecitabine + XRT (SCOPE trial protocol)

Cisplatin 60mg/m2 IV day 1

+

Capecitabine 625mg/m2 oral bd days 1-21


Repeat at 21 day intervals for 4 cycles with radiotherapy concurrent with cycles 3 and 4





guidelines




Metastatic

Cisplatin/5FU Cisplatin 80mg/m2 IV day 1

Fluorouracil 1g/m2 IV over 24hrs days 1-4

or


Repeat at 21 day intervals, max 4-6 cycles








guidelines







Gastric / Adenocarcinomas of Gastro-oesophageal junction Carcinoma

Neoadjuvant / Adjuvant

For patients with operable cancers after initial staging

ECF/X x 3 cycles Surgery -- ECF/X x 3 cycles

ECF/X Epirubicin 50mg/m2 IV day 1


Fluorouracil 200mg/m2 / day via continuous IV infusion for 21 days

or

Capecitabine 625mg/m2 bd days 1-21







guidelines




Adjuvant

EOF/X Epirubicin 50mg/m2 IV day 1

Oxaliplatin 130mg/m2 IV day 1


or



Repeat at 21 day intervals for a maximum of 6 cycles





guidelines







Locally advanced / metastatic

ECF/X Epirubicin 50mg/m2 IV day 1



or



Repeat at 21 day intervals for a maximum of 4-6 cycles


Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated


guidelines




EOF/X Epirubicin 50mg/m2 IV day 1



or











guidelines




Cisplatin/fluoropyrimidine/Herceptin

Cisplatin 80mg/m2 IV

day 1

Fluorouracil 1g/m2 over 24hrs IV days 1-4

or



Herceptin 8mg/kg IV day 1 loading dose

6mg/kg IV every 21 days until progression

Criteria PS 0-1

Cr Cl > 50ml/min

HER 2 status IHC 3+ or FISH positive





guidelines







*Cisplatin/Teysuno

Cisplatin 75mg/m2 IV

day 1

Teysuno 25mg/m2 bd po for 21 days

Repeat at 28 day intervals for up to 6 cycles

Criteria PS 0-1

Cr Cl > 50ml/min

Intolerant of capecitabine / 5FU or at high risk of cardiac toxicity





guidelines




*available via the off protocol mechanism

Second line

Irinotecan 250mg/m2 IV day one of a 21 day cycle repeat x 4 cycles

Option to increase to 350mg/m2 if well tolerated

atropine 600micrograms s/c prior to irinotecan










Pancreatic cancer

Adjuvant

Fluorouracil+Folinic acid Fluorouracil 425mg/m2 IV daily days 1-5

Folinic acid 50mg IV daily days 1-5

Cycles are repeated at 28 days for 6 cycles.

NB: For patients over 70yrs and those with borderline performance status the dose of Fluorouracil should

be reduced to 370mg/m2 per day.







Gemcitabine 1g/m2 IV weekly for 3 weeks followed by one week break

Repeat 28 day cycles for up to 6 cycles.

Criteria PS 0-2

R0, R1 resection M0




NB: transaminases may rise during gemcitabine therapy




Advanced

First line

Gemcitabine + Capecitabine

Gemcitabine 1g/m2 IV days 1, 8, 15

Capecitabine 825mg/m2 po bd for 21 days


Repeat 28 day intervals for up to 6 cycles.




Criteria PS 0-1







CA19-9 every 4 weeks

Day 8 or 15 Platelets 75 99 x109/l continue at full dose

Platelets < 75x109/l omit gemcitabine


Repeat 28 day cycles for up to 6 cycles.

or

IV weekly for seven weeks followed by one week break for first

cycle then 3 weeks on, one off as above.

Criteria PS 0-2








Day 8 or 15 Platelets 75 99 x109/l continue at full dose

Platelets < 75x109/l omit gemcitabine

Second line

Ox-Cap Oxaliplatin 85 mg/m2 IV day 1

Capecitabine 900mg/m2 oral bd x 9 days


Repeat at 14 day intervals for 6 cycles then reassessment

Criteria PS 0-2

Relapse < 6 months post adjuvant chemotherapy

Progression free interval > 3 months following first line therapy








FBC and creatinine prior to each cycle

Normal FBC limits for administration apply with the exception that the lower limit for

platelets for administration of Ox-Cap is 75 x 109/l

OxMdG Oxaliplatin 85 mg/m2 IV day 1

Folinic acid 350mg flat dose two hour IV infusion day 1

Fluorouracil 400mg/m2

15 minute IV bolus day 1

Fluorouracil 2400mg/m2 46hr IV infusion start day 1


Avoid in patients with pre-existing neuropathy







platelets for administration of OxMdG is 75 x 109/l




Cholangiocarcinoma / Gall Bladder Carcinoma

Advanced

Gemcitabine + Cisplatin

Gemcitabine 1000mg/m2 day 1 and 8

Cisplatin 25mg/m2 day 1 and 8


Criteria PS 0-1












Repeat 28 day cycles for 4- 6 cycles.

Criteria PS 0-2








ECF/EOX Epirubicin 50mg/m2 IV day 1


Fluorouracil 200mg/m2 / day via continuous IV infusion

or










guidelines







Hepatocellular carcinoma*

Sorafenib Sorafenib Initial dose 200mg bd

increasing to 400mg bd over 4 weeks to 400mg bd oral continuously

Continue until disease progression

Criteria

PS 0-2

Normal bilirubin

Transaminases < 2xULN

Normal renal function


FBC, U/Es, LFTs prior to each cycle


Discontinue if deteriorating renal or liver function


*NB Available via the Cancer Drugs




Neuroendocrine tumours

High mitotic rate, anaplastic histology, clinically aggressive

Etoposide / cisplatin Etoposide 120mg/m2 IV days 1-3

Cisplatin 70mg/m2 IV days 1

Repeat at 21 day intervals max 6 cycles

Criteria PS 0-1

Cr cl > 50ml/min

Patients with rapidly progressive disease





guidelines




Low mitotic rate, well differentiated histology, clinically indolent

Somatostatin short acting analogue titrated to achieve maximum benefit then switch to

long acting preparation

Pancreatic neuroendocrine tumours

*Everolimus (Afinitor) 10mg oral daily


Ensure normal renal and hepatic function prior to each cycle 1

Where renal / hepatic function are abnormal treatment is at physician

discretion



Criteria First or Second line therapy

*NB Available via the Cancer Drug Fund

*Sunitinib (Sutent) 37.5mg oral daily





Ensure normal renal and hepatic function prior to each cycle 1

Where renal / hepatic function are abnormal treatment is at physician

discretion



Criteria No prior anti-VEGF therapy

*NB Available via the Cancer Drugs Fund

Progression on first line therapy

Streptozotocin/Doxorubicin

Streptozotocin 500mg/m2 IV days 1-5 repeat every 6 weeks

Doxorubicin 50mg/m2 IV day 1 repeat every 3 weeks







*Octreotide Octreotide LAR 20-30mg IM monthly

Criteria non-functioning neuroendocrine tumour of mid gut or uncertain primary origin

Locally inoperable or metastatic disease

Well differentiated histology

*Available via the Cancer Drugs Fund




Colorectal

Adjuvant

5FU/FA Fluorouracil 370mg/m2 IV + folinic acid 50 mg IV weekly x 24 weeks





FBC prior to every fourth week


Capecitabine 1250mg/m2 oral twice daily for 14 days followed by 7 days off

Consider 1000mg/m2 for patients over 70yrs


Repeat at 21 days from day 1 for eight cycles.






Repeat creatinine if clinically indicated


XELOX Oxaliplatin 130 mg/m2 IV day 1




Consider carefully in patients with pre-existing neuropathy

Consider omitting oxaliplatin if persistent neuropathy develops.






subsequent cycles if clinically indicated.



Normal FBC limits for administration apply.







Consider carefully in patients with pre-existing neuropathy

Consider omitting oxaliplatin if persistent neuropathy develops.











Rectal cancer - Chemoradiation

5FU + XRT Fluorouracil 1000mg/m2 IV days 1-4 and 22-26 (or final week)

Or

Fluorouracil 300mg/m2 + Folinic acid 50mg

IV weekly during the radiotherapy







Capecitabine + XRT Capecitabine 825mg/m2 oral bd Mon-Fri during XRT






FBC each week during chemotherapy


5FU/FA Fluorouracil 300mg/m2 IV + folinic acid 50 mg IV weekly during XRT





FBC prior to every fourth week





Advanced Colorectal Cancer

First line

Single agent

MdG MdG: Folinic acid 350mg flat dose two hour IV infusion day 1




repeat at 14 day intervals, re-evaluate after 6 cycles.







Capecitabine 1250mg/m2 oral twice daily for 14 days

Consider 1000mg/m2 if age >70yrs




Ensure normal renal and hepatic function prior to cycle 1 if clinically indicated




Raltitrexed (Tomudex) 3mg/m2 IV repeat at 21 day intervals for a maximum of 6 cycles

Criteria: Patients intolerant of fluoropyrimidines





Ensure normal renal and hepatic function prior to cycle 1 if clinically indicated




Combination chemotherapy

IrinMdG Irinotecan 180mg/m2 IV + atropine 600micrograms s/c prior to irinotecan

MdG: Folinic acid 350mg flat dose two hour IV infusion day 1



Fluorouracil 2400mg/m2 46hr infusion start day 1


Review after 12 weeks and consider continuing to 24 weeks if:

SD / response.

Acceptable toxicity

Criteria: PS 0-2







I-Cap Irinotecan 180mg/m2 IV + atropine 600micrograms s/c prior to irinotecan





SD / response.

Acceptable toxicity

Criteria: PS 0-1
























Ox-Cap Oxaliplatin 85 mg/m2 IV day 1











platelets for administration of Ox-Cap is 75 x 109/l

XELOX Oxaliplatin 130 mg/m2 IV day 1













Normal FBC limits for administration apply.

OxMdG + Cetuximab

Oxaliplatin 85 mg/m2 IV day 1


Fluorouracil 400mg/m2 15 minute IV bolus day 1


Cetuximab Week 1 500mg/m2 IV day 1 over 2 hours using 0.2um in-line filter

Then 500mg/m2 IV over 1 hour every 2 weeks

Premedication Dexamethasone 8mg

Chlorphenamine 10mg

Ranitidine 150mg






FBC and biochemistry prior to each cycle



Criteria KRAS wild type cancer

PS 0-1

Metastatic disease confined to the liver and potentially resectable if downsized

Primary resected or resectable





IrinMdG + Cetuximab

Irinotecan 180mg/m2 IV + atropine 600micrograms s/c prior to irinotecan




Fluorouracil 2400mg/m2 46hr infusion start day 1




Chlorphenamine 10mg

Ranitidine 150mg

Repeat at 14 day intervals.


SD / response.

Acceptable toxicity








Criteria KRAS wild type cancer

PS 0-1

Metastatic disease confined to the liver and potentially resectable if downsized

Primary resected or resectable

*Bevacizumab 14 day schedules: Bevacizumab 5mg/kg IV infusion

21 day schedules Bevacizumab 7.5mg/kg IV infusion

Criteria Advanced colorectal cancer

First line chemotherapy

With oxaliplatin or Irinotecan based combination chemotherapy





Second / third line chemotherapy

Irinotecan + MdG (see above)

Oxaliplatin + MdG (see above)

I-Cap (see above)

Ox-Cap (see above)

Irinotecan 180mg/m2 IV day 1 of a 14 day cycle


or

350mg/m2 IV day one of a 21 day cycle



Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if





*Bevacizumab 14 day schedules: Bevacizumab 5mg/kg IV infusion

21 day schedules Bevacizumab 7.5mg/kg IV infusion

Criteria Advanced colorectal cancer

Second line chemotherapy

With oxaliplatin based combination chemotherapy


*Irinotecan + Cetuximab

Criteria

- Must have KRAS wild type cancers

- Previously responded to chemotherapy

- Second or third line chemotherapy

- Performance status (0-1)






Irinotecan 180mg/m2 IV every 2 weeks + atropine 600micrograms s/c


Chlorphenamine 10mg

Ranitidine 150mg



* Cetuximab single agent

Criteria

- Must have KRAS wild type cancers

- Previously responded to chemotherapy

- Third line chemotherapy

- Performance status (0,1)




Chlorphenamine 10mg

Ranitidine 150mg



MMC + MdG Mitomycin-C 7mg/m2 IV day 1 repeat every 6 weeks (max 4 doses)

+

Folinic acid 350mg flat dose two hour infusion




Repeated at 14 day intervals










MMC + Capecitabine Mitomycin-C 7mg/m2 IV day 1 repeat every 6 weeks, max 4 doses

Capecitabine 1000mg/m2 oral bd for 14 days repeat at 21 day intervals











Anal Carcinoma

Localised squamous carcinoma of the anus

Combined XRT + chemotherapy

Mitomycin C 12mg/m2 IV day 1 only (max 20mg)

Fluorouracil 1000mg/m2 IV over 24hrs days 1-4

Fluorouracil 1000mg/m2 IV over 24hrs daily x 4 during final week of XRT

or

Capecitabine 825mg/m2 bd oral on each XRT treatment day








Palliative / Metastatic

Cisplatin/5FU Cisplatin 60mg/m2 IV (max 120mg) day 1

Fluorouracil 1g/m2 IV over 24hrs days 1-4

or


Repeat at 21 day intervals max 4 courses





guidelines







Mitomycin C / Fluoropyrimidine

Mitomycin C 7mg/m2 IV day 1 repeat every 6 weeks, max 4 cycles

Fluorouracil 1000mg/m2 IV over 24hrs days 1-4 repeat at 21 day intervals

or

Capecitabine 1000mg/m2 bd po days 1-14 repeat at 21 day intervals










Gynaecological Cancer

Epithelial Ovarian Cancer

First Line Chemotherapy

Paclitaxel/Carboplatin Paclitaxel 175mg/m2 IV over 3 hours

Carboplatin AUC 5/6 IV over 1 hour

Paclitaxel premedication Chlorphenamine 10mg

Dexamethasone 20mg

Ranitidine 50mg

Repeat at 21 day intervals maximum 6 courses

Criteria Stage Ib-IV

Minimal residual disease / bulk residual disease

PS 0-1

Cr Cl > 50ml/min




Calculate or measure creatinine clearance prior to first cycle and before subsequent

cycles if clinically indicated


CA125 prior to each cycle



*Paclitaxel/Carboplatin/Bevacizumab

Paclitaxel 175mg/m2

IV over 3 hours

Carboplatin AUC 5/6 IV over 1 hour

Bevacizumab 7.5mg/kg

Paclitaxel premedication Chlorphenamine 10mg

Dexamethasone 20mg

Ranitidine 50mg

Repeat at 21 day intervals maximum 6 cycles chemotherapy max 18 cycles bevacizumab

Criteria Stage III (residual disease >1cm) or IV

PS 0-1

Cr Cl > 50ml/min













*Available via the cancer drugs Fund

or

Carboplatin Carboplatin AUC 5/6 x (GFR + 25) IV at 21-28 day intervals x max 6 cycles










Second line chemotherapy

Relapse > 6 months post platinum

Single agent carbopla

protokol kemoterapi

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