Gastrointestinal Cancer Chemo Protocols

8/2/2019 Gastrointestinal Cancer Chemo Protocols

1/21

Department of Medical Oncology Chemotherapy Protocols

3rd

Edition 34

Protocol: Modified Machover

Indications: Colonic Cancer - Adjuvant

Schedule:Drug Dose iv/infusion/oral qCalcium Folinate 50mg iv Days 1-55-Fluorouracil 370mg/m2 iv Days 1-5

Cycle frequency: Every four weeks Total number of cycles: 6

Dose modifications: Discuss with Consultant

Administration and safety:

Anti-emetic group Low

Delay if neutrophils < 1.5 x 109/L or platelets < 100 x 109/L for one week

Suck ice before and during 5-FU injection

Calcium Folinate given first

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea,mucositis, cardiotoxicity, conjunctivitis, severe diarrhoea, palmar-plantar syndrome,infertility

Symptomatic treatment of side effects: Prophylactic mouth care, anti-diarrhoeals,pyridoxine cream

InvestigationsPre-treatment:

History and Examination

Performance score, weight

FBC

U & Es, LFTs, creatinine, urate

LDH, CEA

ECG

Staging investigations as per protocol

Prior to each cycle:


FBC

U & Es, LFTs, creatinine LDH, CEA

Mid Treatment: Re-assess after every two cycles

Post Treatment: Review in Medical Oncology Clinic 4 weeks after last cycle

Reference: Quasar 2000. Lancet, 6; pages 1588-1596


2/21


3rd

Edition 35

Protocol: Weekly QUASAR

Indications: Colonic Cancer Adjuvant

Schedule:Drug Dose iv/infusion/oral qCalcium Folinate 50mg iv Day 15-Fluorouracil 370mg/m2 iv Day 1

Cycle frequency: Every week Total number of cycles: 30












FBC


LDH, CEA

ECG




FBC

U & Es, LFTs, creatinine LDH

Mid Treatment: Re-assess after every 6 cycles


Reference: Quasar 2000. Lancet, 6; pages 1588-1596


3/21


3rd

Edition 36

Protocol: Mayo

Indications: Colonic Cancer - Adjuvant

Schedule:Drug Dose iv/infusion/oral qCalcium Folinate 50mg

iv Days 1-5

5-Fluorouracil 425mg/m2 iv Days 1-5


Dose modifications: Discuss with Consultant. If toxicity experienced, or if delayed for > 1week, reduce 5-FU dose by approximately 20%



Delay if neutrophils < 1.5 x 109/L or platelets < 100 x 10

9/L for one week






History and Examination Performance score, weight

FBC


LDH, CEA

ECG




FBC U & Es, LFTs, creatinine

LDH



Reference: OConnell et al, 1997. J. Clin. Oncol., 15; pages 246-250


4/21


3rd

Edition 37

Protocol: FLOX

Indications: Colon Cancer (Adjuvant)

Schedule:Drug Dose iv/infusion/oral qOxaliplatin 85mg/m

2250mls 5% dex/2hrs Days 1, 15 & 29

Calcium Folinate 350mg 250mls 5% dex/2hrs Days 1,8,15,22,29,365-Fluorouracil 500mg/m

2 iv (5 min) Days 1,8,15,22,29,36

Cycle frequency: Every eight weeks Total number of cycles: 3



Anti-emetic group - Moderately high with Oxaliplatin


9/L

Oxaliplatin and Calcium Folinate given concurrently

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, cardiotoxicity, peripheral neuropathy, paraesthesia, severediarrhoea, pharyngolaryngeal dysaesthesia, palmar-plantar syndrome, conjunctivitis,carcinogenesis, infertility

Symptomatic treatment of side effects: Prophylactic mouth care, anti-diarrhoeals


History and Examination (CNS examination)

Performance score, weight FBC

U & Es, LFTs, Ca2+

, creatinine, urate

LDH, CEA

ECG



CNS examination


FBC U & Es, LFTs, Ca2+

, creatinine

LDH,


Reference: Wolmark et al, 2005. J. Clin. Oncol., 23(16s); abstract LBA3500


5/21


3rd

Edition 38

Protocol: Modified de Gramont

Indications: Colonic Cancer - Metastatic

Schedule:Drug Dose iv/infusion/oral qCalcium Folinate 350mg

250mls N. Saline/2hrs Day 1

5-Fluorouracil 400mg/m2 iv (5 mins) Day 15-Fluorouracil 2.8g/m2 4L N. Saline/46hrs Days 1 & 2

Cycle frequency: Every two weeks Total number of cycles: up to 12





9/L

Suck ice before and during 5-FU bolus injection


Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea,mucositis, cardiotoxicity, severe diarrhoea, conjunctivitis, palmar-plantar syndrome,infertility




FBC


LDH, CEA

ECG





LDH,

Mid Treatment: Re-assess after every four cycles


Reference: Cheeseman et al, 2002. Br. J. Cancer, 87; pages 393-399


6/21


3rd

Edition 39

Protocol: Irinotecan

Indications: Colonic Cancer Palliative, Recurrent

Schedule:Drug Dose iv/infusion/oral qIrinotecan 350mg/m

2250mls 5% dex/90min Day 1

Cycle frequency: Every three weeks Total number of cycles: 6



Anti-emetic group Moderately high

Delay if neutrophils < 1.5 x 109/L or platelets < 100 x 109/L

Pre-medication with atropine 300 g (0.5 mls) s/c, if required

Start at 250mg/ m2

if unwell, or PS=2, or aged 70 years +

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, amenorrhoea, severe diarrhoea, increased sweating andsalivation, flushing, abdominal cramps, infertility

Symptomatic treatment of side effects: Mouth care, Loperamide, encourage oral fluids




FBC


LDH, CEA

ECG




FBC

U & Es, LFTs, creatinine

LDH,



Reference: Rougieret al, 1997. J. Clin. Oncol., 15; pages 251-260


7/21


3rd

Edition 40

Protocol: Oxaliplatin



2250mls 5% dex/2hrs Day 1




Anti-emetic group Moderately high


Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, peripheral neuropathy, paraesthesia, diarrhoea,pharyngolaryngeal dysaesthesia, carcinogenesis, infertility

Symptomatic treatment of side effects: Prophylactic mouth care, anti-diarrhoeals,


History and Examination (CNS mandatory)


FBC

U & Es, LFTs, Mg2+, Ca2+, creatinine, urate

LDH, CEA

ECG



CNS examination


FBC

U & Es, LFTs, Mg2+, Ca2+, creatinine

LDH,



Reference: Ducreux et al, 2004. Ann. Oncol., 15; pages 467-473


8/21


3rd

Edition 41

Protocol: Oxaliplatin with Modified de Gramont(FOLFOX6)




Calcium Folinate 350mg 250mls 5% dex/2hrs Day 15-Fluorouracil 400mg/m

2 iv (5mins) Day 15-Fluorouracil 2.4g/m

24L N. Saline/46hrs Days 1 & 2




Anti-emetic group Moderately high with Oxaliplatin


9/L

Oxaliplatin and Calcium Folinate given concurrently Plan Bevacizumab if appropriate

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, (alopecia), cardiotoxicity, peripheral neuropathy, paraesthesia, severediarrhoea, pharyngolaryngeal dysaesthesia, carcinogenesis, infertility

Symptomatic treatment of side effects: Prophylactic mouth care, anti-diarrhoeals


History and Examination (CNS mandatory) Performance score, weight

FBC

U & Es, LFTs, Mg2+, Ca2+, creatinine, urate

LDH, CEA

ECG



CNS examination


U & Es, LFTs, Mg2+, Ca2+, creatinine

LDH,

Mid Treatment: Restage after 6 cycles


Reference: Cheeseman et al, 2002. Br. J. Cancer, 87; pages 393-399


9/21


3rd

Edition 42

Protocol: Irinotecan with Modified de Gramont (FOLFIRI)



2250mls 5% dex/30mins Day 1

Calcium Folinate 350mg 250mls N. Saline/2hrs Day 15-Fluorouracil 400mg/m






Anti-emetic group Moderately high with Irinotecan


9/L

Pre-medication with atropine 300g (0.5mls) s/c may be required

Suck ice before and during 5-FU bolus injection

Plan Bevacizumab if appropriate

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, cardiotoxicity, severe diarrhoea, amenorrhoea, increasedsweating and salivation, flushing, abdominal cramps, infertility

Symptomatic treatment of side effects: Prophylactic mouth care, Loperamide, encourageoral fluids


History and Examination (CNS mandatory)


FBC


LDH, CEA

ECG



CNS examination


FBC


LDH,

Mid Treatment; Restage after 6 cycles


Reference: Tournigandet al

, 2004. J. Clin. Oncol., 22 ; pages 229-237


10/21


3rd

Edition 43

Protocol: Capecitabine

Indications: Colonic Cancer Adjuvant or Metastatic

Schedule:Drug Dose iv/infusion/oral qCapecitabine 1250mg/m

2bd oral Days 1-14

Cycle frequency: Every three weeks Total number of cycles: 8 (if adjuvant)





Ensure patient education regarding palmar-plantar syndrome

Round Capecitabine tablets to the nearest 150mg or 500mg (see data sheet)

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, hair thinning, amenorrhoea, diarrhoea, skin rash, palmar-plantarsyndrome, infertility.

Symptomatic treatment of side effects: Mouth care




FBC


LDH

ECG




FBC


LDH


Post Treatment: Review in Medical Oncology outpatients 4 weeks after last cycle

Reference: Van Cutsem et al, 2000. J. Clin. Oncol., 18; pages 1337-1345


11/21


3rd

Edition 44

Protocol: Irinotecan/Capecitabine (XELIRI)

Indications: Colonic Cancer Metastatic


2250mls 5% dex/30min Day 1

Capecitabine 1000mg/m2 bd oral Days 1-14

Cycle frequency: Every three weeks Total number of cycles: 6 -12



Anti-emetic group - Moderately high with Irinotecan


Pre-medication with atropine 300ug (0.5mls) s/c may be required


Round Capecitabine dose to nearest 500mg or 150mg (see data sheet)


Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, amenorrhoea, peripheral neuropathy, severe diarrhoea,increased sweating and salivation, flushing, hypersensitivity reactions, skin rash,cardiotoxicity, palmar-plantar syndrome, fluid retention, hepatic dysfunction, infertility





FBC


LDH

ECG





LDH



Reference: Park et al, 2004. Oncology, 66; pages 353-357


12/21


3rd

Edition 45

Protocol: Oxaliplatin/Capecitabine (XELOX)

Indications: Colonic Cancer Metastatic



Capecitabine 1000mg/m2 bd oral Days 1-14

Cycle frequency: Every three weeks Total number of cycles: 6 -12



Anti-emetic group - Moderately high with Oxaliplatin



Round Capecitabine dose to nearest 500mg or 150mg (see data sheet)


Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, amenorrhoea, peripheral neuropathy, severe diarrhoea,paraesthesia, pharyngolaryngeal dysaesthesia,, hypersensitivity reactions, skin rash,cardiotoxicity, palmar-plantar syndrome, hepatic dysfunction, infertility





FBC


LDH

ECG





LDH



Reference: Cassidy et al, 2004. Clin. Oncol., 22; pages 2084-2091


13/21


3rd

Edition 46

Protocol: Cetuximab (Erbitux)

Indication: Colorectal cancer - metastatic

Schedule:Drug Dose iv/infusion/oral qCetuximab 400mg/m

2iv (2hrs) Day 1as per datasheet

Cetuximab 250mg/m2 iv (1hr) weekly

as per datasheet

Cycle frequency: Every week Total number of cycles: Indefinite

Dose modification: Discuss with Consultant




9/L

Pre-med with Chlorpheniramine

With Irinotecan (180 350mg/m2 ) every three weeks

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea,hyper-sensitivity reaction, carcinogenesis, infertility, allergic-like reaction, bronchospasm,hypotension, chills/fevers, rigors, skin rash, asthenia, stomatitis, anorexia, constipation,acne

Symptomatic treatment of side effects: Supportive therapy

Investigations

Pre-treatment: History and Examination


FBC


LDH

ECG




FBC


LDH


Reference: Cunningham et al, 2004. N. Engl. J. Med., 351; pages 337-345


14/21


3rd

Edition 47

Protocol: Bevacizumab (Avastin)

Indication: Colorectal cancer - metastatic

Schedule:Drug Dose iv/infusion/oral qBevacizumab 5mg/kg 100mls N. Saline each cycle

(as below)

Cycle frequency: Every 2 weeks Total number of cycles: Indefinite

OR

Drug Dose in/infusion/oral qBevacizumab 7.5mg/kg 100mls N. Saline each cycle

(as below)

Cycle frequency: Every 3 weeks Total number of cycles: Indefinite

Dose modification: Discuss with Consultant




1st infusion 90mins; 2nd infusion 60mins; 3rd infusion 30mins

If the patient is a candidate for surgery, administer 4 cycles only

Toxicities: Hypersensitivity reaction, allergic-like reaction, hypertension, skin rash,proteinuria, thromboembolism, impaired wound healing, GI perforation

Symptomatic treatment of side effects: Supportive therapy



Performance score, weight, blood pressure, proteinuria

FBC


LDH

ECG



Performance score, weight, blood pressure, proteinuria

FBC


LDH


Reference: Hurwitz et al, 2004. N. Engl. J. Med., 350; pages 2335-2342Milleret al, 2005. J. Clin. Oncol., 23; pages 792-799


15/21


3rd

Edition 48

Protocol: Modified OConnell (5-Fluorouracil/RT)

Indication: Rectal Cancer Adjuvant

Schedule:Drug Dose iv/infusion/oral q5-Fluorouracil 425mg/m

2iv Days 1-5

Radiotherapy 45Gy 5 weeks Start day 56With 5-Fluorouracil 225mg/m

2/24hrs continuous infusion for 5 weeks


Dose modification: Discuss with Consultant. If toxicity experienced, or if delayed for > 1weeks, reduce 5-FU dose by 20%




9/L for one week




InvestigationsPre-treatment


FBC


LDH, CEA

ECG




FBC


LDH,



Reference: OConnell et al, 1994, N. Engl. J. Med., 331; pages 502-507


16/21


3rd

Edition 49

Protocol: ECF (Epirubicin/Cisplatin/5-Fluorouracil)

Indications: Oesophageal/Gastric Neoadjuvant, Metastatic, Locally advanced

Schedule:Drug Dose in/infusion/oral qEpirubicin 50mg/m

2iv Day 1

Cisplatin 60mg/m2 1L N. Saline/2hrs Day 15-Fluorouracil 200mg/m2/24hrs continuous infusion Days 1-21




Anti-emetic group High


9/L

Ensure adequate renal function

Hickman line required

Pre & post hydration, mannitol, potassium & magnesium

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, Cardiotoxicity, peripheral neuropathy, palmar-plantarsyndrome, Nephrotoxicity, diarrhoea, carcinogenesis, infertility

Symptomatic treatment of side effects: Mouth care, anti-diarrhoeals, pyridoxine




FBC

U & Es, LFTs, Mg2+, Ca2+, creatinine, urate, creatinine clearance

LDH

ECG




FBC U & Es, LFTs, Mg

2+, Ca

2+, creatinine

LDH

Mid Treatment: Re-assess after 3 cycles (endoscopy+/- radiology)


Reference: Findlay et al, 1994. Ann, Oncol., 5; pages 609-616


17/21


3rd

Edition 50

Protocol: CF (Cisplatin/5-Fluorouracil)

Indications: Oesophageal Neoadjuvant

Schedule:Drug Dose iv/infusion/oral qCisplatin 75mg/m

21L N. Saline/2hrs Day 1

5-Fluorouracil 1g/m2/24 hrs continuous infusion Days 1-4

Cycle frequency: Every three weeks Total number of cycles: 2(neoadjuvant)





9/L



Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, cardiotoxicity, peripheral neuropathy, palmar-plantarsyndrome, nephrotoxicity, ototoxicity, diarrhoea, carcinogenesis, infertility





FBC

U & Es, LFTs, Mg2+

, Ca2+

, creatinine, urate, creatinine clearance

LDH

ECG




FBC

U & Es, LFTs, Mg

2+

, Ca

2+

, creatinine LDH

Mid Treatment: Re-assess after 2 cycles (endoscopy +/- radiology)


Reference: MRC Oesophageal Cancer WP, 2002. Lancet, 359; pages 1727-1733


18/21


3rd

Edition 51

Protocol: Herskovic (Cisplatin/5-Fluorouracil/RT)

Indication: Oesophageal Locally advanced (inoperable)

Schedule:Drug Dose iv/infusion/oral qCisplatin 75mg/m

21L N. Saline/2hrs Day 1

5-Fluorouracil 1g/m2/24hrs continuous infusion Days 1-4Radiotherapy 50Gy 5 weeks Start Day 1

Cycle frequency: Every four weeks Total number of cycles: 4(First 2 cycles with RT)





9/L



Concurrent radiotherapy may be necessary

Doses may change according to radiotherapy schedule

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea &vomiting, mucositis, alopecia, cardiotoxicity, peripheral neuropathy, palmar-plantarsyndrome, nephrotoxicity, ototoxicity, diarrhoea, carcinogenesis, infertility





FBC

U & Es, LFTs, Mg2+, Ca2+, creatinine, urate, creatinine clearance

LDH

ECG


Prior to each cycle: Performance score, weight

FBC

U & Es, LFTs, Mg2+

, Ca2+

, creatinine

LDH

Mid Treatment: Review in Medical Oncology post-radiotherapy


Reference: Herskovic et al, 1992, N. Engl. J. Med., 326; pages 1593-1598


19/21


3rd

Edition 52

Protocol: MMC with Modified de Gramont

Indications: Gastric Cancer Advanced

Schedule:Drug Dose iv/infusion/oral qMitomycin C 6mg/m

2iv Day 1

Calcium Folinate 350mg 250mls N. Saline/2hrs Day 15-Fluorouracil 400mg/m






Anti-emetic group Moderate


9/L

Suck ice before and during 5-Fluorouracil bolus injection

Ensure serum creatinine is within normal levels

Blood film is normal i.e. no red cell fragmentation

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea,mucositis, cardiotoxicity, severe diarrhoea, infertility, conjunctivitis, palmar-plantarsyndrome





FBC


LDH

ECG




FBC


LDH

Blood film


Post Treatment: Review in Medical Oncology Clinic 4 weeks after last cycle.

Reference: Ross et al, 1997, Ann Oncol., 8; pages 995-1001


20/21


3rd

Edition 53

Protocol: Modified MacDonald (5-Fluorouracil/FA/RT)

Indications: Gastric Cancer Adjuvant

Schedule:Drug Dose iv/infusion/oral qCalcium Folinate 40mg/m

2iv Days 1-5

5-Fluorouracil 425mg/m2 iv Days 1-5Radiotherapy 45Gy 5 weeks Start day 29Calcium Folinate 20mg/m

2iv First 4 & last 3 days of RT

5-Fluorouracil 400mg/m2

iv First 4 & last 3 days of RT

Cycle frequency: Every four weeks Total number of cycles: 3(1 cycle prior to RT)

Dose modifications: Discuss with Consultant. If toxicity experienced, or if delayed for> 1 week, reduce 5-FU dose by 20%

Administration and safety: Anti-emetic group Low





Symptomatic treatment of side effects: Prophylactic mouth care, anti-diarrheals, pyridoxine

cream




FBC


LDH,

ECG




FBC


LDH,


Reference: Macdonald et al, 2001. N. Engl. J. Med., 345; pages 725-730


21/21


Protocol: Gemcitabine

Indications: Pancreatic Cancer Palliative

Schedule:Drug Dose iv/infusion/oral qGemcitabine 1000mg/m

2200mls N. Saline/30mins Days 1, 8 &15




Anti-emetic group - Moderate


If unable to tolerate, omit day 15 and give every 3 weeks

Toxicities: Myelosuppression and risk of neutropenic sepsis or haemorrhage, nausea,mucositis, amenorrhoea, rash, flu-like symptoms, hair thinning, diarrhoea, infertility





FBC


LDH, CA19-9

ECG




FBC


LDH, CA19-9

Mid Treatment: After every two cycles


Reference: Burris et al, 1997. J. Clin. Oncol., 15; pages 2403-2413

Documents

Gastrointestinal Cancer Chemo Protocols