Thames Valley Chemotherapy Regimens

Transcription

1 Chemotherapy Regimens Lung Cancer

2 Notes from the editor All chemotherapy regimens, and associated guidelines eg antiemetics and dose bands are available on the Network website Any correspondence about the regimens should be addressed to: Sally Coutts, Cancer Pharmacist, Acknowledgements These regimens have been compiled by the Network Pharmacy Group in collaboration with the Lung CAG with key contributions from Dr Nick Bates, Consultant Oncologist, BHT Dr Paul Rogers, Consultant Oncologist, RBFT Dr Joss Adams, Consultant Oncologist, RBFT Prof Denis Talbot, Consultant Oncologist, OUH Cancer Network. All rights reserved. Not to be reproduced in whole or in part without the permission of the copyright owner. Network Chemotherapy Regimens Lung Cancer 2

3 Chemotherapy Regimens Lung Cancer Network Chemotherapy regimens used in the management of Lung Cancer Date published: January 2019 Date of review: January 2021 Chemotherapy Regimens Name of regimen Indication Page List of amendments to this version 5 ACE Small Cell lung 6 CAV Small Cell lung 8 Carboplatin Etoposide Small cell lung 10 Cisplatin (75) Etoposide (100) with concurrent RT Small cell lung 12 Cisplatin (60) Etoposide (120) Small cell lung 14 Topotecan oral Small cell lung 16 Afatinib Non small cell lung 18 Alectinib Non small cell lung 20 Atezolizumab Non small cell lung 23 Ceritinib Non small cell lung 28 Cisplatin (50) Etoposide (50) with concurrent RT Non small cell lung 31 Cisplatin Vinorelbine with concurrent RT Non small cell lung 37 Gemcitabine Cisplatin Non small cell lung 35 Cisplatin 40 RT Non small cell lung 37 Crizotinib Non small cell lung cancer 39 Docetaxel 75 Non small cell lung 41 Docetaxel (75) Cisplatin (75) Non small cell lung 43 Docetaxel (75) Carboplatin Non small cell lung 45 Erlotinib Non small cell lung 47 Gefitinib Non small cell lung 49 Gemcitabine (1200) Carboplatin Non small cell lung and small cell lung 51 Gemcitabine Non small cell lung 53 Nintedanib Docetaxel Non small cell lung 55 Nivolumab Non-small cell lung 58 Chemotherapy regimens Lung Cancer 3

4 Name of regimen Name Page of regimen Osimertinib Non small cell lung 62 Paclitaxel 80mg (days 1, 8 and 15) Non small cell lung 64 Pembrolizumab 1 st line Non small cell lung 66 Pembrolizumab previous treatment Non small cell lung 68 Vinorelbine (25) Carboplatin Non small cell lung 70 Vinorelbine (25) Cisplatin (80) Non small cell lung 72 Vinorelbine Non small cell lung 74 Vinorelbine (oral) Non small cell lung 75 Vinorelbine elderly (oral) Non small cell lung 77 Vinorelbine (oral) Cisplatin Non small cell lung 79 Vinorelbine (oral) Carboplatin Non small cell lung 82 Carboplatin Pemetrexed Non small cell lung, Mesothelioma 84 Cisplatin Pemetrexed Non small cell lung, Mesothelioma 86 Pemetrexed maintenance Non small cell lung 88 Pre and post hydration regimens 90 Page Indication Chemotherapy regimens Lung Cancer 4

5 List of amendments in this version Regimen type: Lung Tumours Date due for review: January 2021 Previous number: 4.0 This version number: Table 1 Amendments Page Amendment Made/ asked by Diluent volume amendments as per national dose standardisation spoecifications Table 2 New regimens to be approved and checked by CAG included in this version Name of regimen Indication Reason / Proposer Atezolizumab NSCLC CDF Alectinib NSCLC CDF For anti-emetic guidelines: For dose banded chemotherapy standardized product specifications: Chemotherapy regimens Lung Cancer 5

6 ACE (SCLC) Indication: Has been used as first line treatment for SCLC but platinum/etoposide is preferred People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 DOXORUBICIN 40mg/ 2 IV bolus CYCLOPHOSPHAMIDE 600mg/m 2 IV bolus ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes Day 2 ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes Day 3 ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes *doses 48mg to 88mg in 250ml, doses 96mg to 180mg in 500ml sodium chloride 0.9% NB Day 2 and 3 etoposide can be given orally ETOPOSIDE 200mg/m 2 PO but is not recommended as oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary. Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Doxorubicin: Dose reduce in severe renal impairment. Bilirubin 20-50micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit If AST is 2-3 x ULN give 75% dose If AST is >3 x ULN give 50% dose Maximum cumulative dose = 450 mg/m 2 (in normal cardiac function) = 400 mg/m 2 (in patients with cardiac dysfunction or exposed to mediastinal irradiation) Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision ACE Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 6

7 Cyclophosphamide: GFR >20ml/min give 100% dose GFR 10-20ml/min give 75% dose GFR <10ml/min give 50% dose INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Liver function tests (LFT) Serum Creatinine 2) Non urgent blood tests Tests relating to disease response/progression ECG (possibly ECHO) required if patient has preexisting cardiac disease (Doxorubicin) CONCURRENT MEDICATION ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cyclophosphamide may irritate bladder, drink copious volumes of water. Cardiotoxicity Monitor cardiac function to minimise the risk of anthracycline induced cardiac failure. Doxorubicin may be stopped in future cycles if signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. REFERENCES 1. Aisner J et al. Cancer Treat Rep 1982; 66: Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network. ACE Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 7

8 CAV (SCLC) Indication: First line treatment for SCLC in patients not able to tolerate platinum and etoposide (e.g. performance status of 3). Can also be used as second line treatment after relapse. People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 VINCRISTINE 1.3mg/m 2 (max. 2 mg) in 50ml sodium chloride 0.9% IV over 10 mins DOXORUBICIN 40mg/m 2 IV bolus CYCLOPHOSPHAMIDE 750 mg/m 2 IV bolus Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Vincristine: If patient complains of tingling of fingers and/or toes, discuss. Bilirubin 25-51micromol/L or AST u/L give 50% dose Bilirubin >51micromol/L and normal AST give 50% dose Bilirubin >51micromol/L and AST >180u/L omit Doxorubicin: Dose reduce in severe renal impairment. Bilirubin 20-50micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit If AST is 2-3 x ULN give 75% dose If AST is >3 x ULN give 50% dose Maximum cumulative dose = 450 mg/m 2 (in normal cardiac function) = 400 mg/m 2 (in patients with cardiac dysfunction or exposed to mediastinal irradiation) Cyclophosphamide: GFR >20ml/min give 100% dose GFR 10-20ml/min give 75% dose GFR <10ml/min give 50% dose CAV Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 8

9 INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Liver function tests (LFT) Serum Creatinine 2) Non urgent blood tests Tests relating to disease response/progression ECG (possibly ECHO) required if patients has preexisting cardiac disease (Doxorubicin) CONCURRENT MEDICATION ANTIEMETIC POLICY High emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cardiotoxicity Monitor cardiac function to minimise the risk of anthracycline induced cardiac failure. Doxorubicin may be stopped in future cycles if signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. Cyclophosphamide may irritate bladder, drink copious volumes of water. REFERENCES 1. Greco FA et al. Am J Med 1979; 66: Roth BJ et al. J Clin Oncol 1992; 10: Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network. CAV Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 9

10 Carboplatin Etoposide (SCLC) Indication: Standard first line treatment for SCLC People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 CARBOPLATIN AUC 5 infusion in 500ml glucose 5% infusion over 60 minutes Dose (mg) = AUC x (GFR+25) ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes Day 2 ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes Day 3 ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes *doses 48mg to 88mg in 250ml, doses 96mg to 180mg in 500ml sodium chloride 0.9% NB Day 2 and 3 can be given orally ETOPOSIDE 100mg/bd PO but is not recommended as oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary. If days 2 and 3 are given orally the day 1 IV dose should be increased to 120mg/m 2. Ideally EDTA GFR should be used, Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/l If GFR / calculated CrCl = or < 20ml/min contraindicated. Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Carboplatin/ etoposide Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 10

11 INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Ideally EDTA GFR should be used (Carboplatin) Creatinine clearance (GFR) calculated, at the Consultants discretion Liver function tests (LFT) 2) Non urgent blood tests. Tests relating to disease response/progression CONCURRENT MEDICATION FOR PREVENTION Anaphylaxis treatment should be prescribed if the patient has had an anaphylactic episode previously. DEXAMETHASONE 20mg IV bolus CHLORPHENAMINE 10mg IV bolus RANITIDINE 50mg IV bolus Carboplatin should be given at a slower rate e.g. 2-4 hours. ANTIEMETIC POLICY Moderate emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Ototoxicity - monitor Neurotoxicity monitor. REFERENCES 1. Skarlos DV et al. Ann Oncol 1994; 5: Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network. 3. Study 12/14 Carboplatin/ etoposide Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 11

12 Cisplatin (75) Etoposide (100) (SCLC) Indication: Standard first line treatment for SCLC with concurrent radiotherapy People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 Pre-hydration ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes CISPLATIN 75mg/m 2 infusion in 1000ml sodium chloride 0.9% over 2 hours Post hydration Day 2 ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes Day 3 ETOPOSIDE 100mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes *doses 48mg to 88mg in 250ml, doses 96mg to 180mg in 500ml sodium chloride 0.9% NB Day 2 and 3 etoposide can be given orally ETOPOSIDE 200mg/m 2 /day but is not recommended as oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary. Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min omit dose If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Cisplatin 75 / etoposide 100 Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 12

13 INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Creatinine clearance (GFR) calculated, or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN regimens. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity ensure adequate pre and post hydration is prescribed. Ototoxicity assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Evans WK et al. J Clin Oncol 1985; 3: Roth BJ et al. J Clin Oncol 1992; 10: Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network. Cisplatin 75 / etoposide 100 Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 13

14 Cisplatin (60) with Etoposide (120) (SCLC) Indication: Standard first line treatment for SCLC at RBH and HWP People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 Pre-hydration ETOPOSIDE 120mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes CISPLATIN 60mg/m 2 infusion in 1000ml sodium chloride 0.9% over 2 hours Post-hydration Day 2 ETOPOSIDE 120mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes Day 3 ETOPOSIDE 120mg/m 2 infusion in 1000ml* sodium chloride 0.9% over 60 minutes *doses 48mg to 88mg in 250ml, doses 96mg to 180mg in 500ml sodium chloride 0.9% NB Day 2 and 3 etoposide can be given orally ETOPOSIDE 240mg/m 2 /day but is not recommended as oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary. Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Cisplatin 60 /etoposide 120 Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 14

15 INVESTIGATIONS 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Creatinine clearance (GFR) calculated, or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests: tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN regimens. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity ensure adequate pre and post hydration is prescribed. Ototoxicity assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Evans WK et al. J Clin Oncol 1985; 3: Roth BJ et al. J Clin Oncol 1992; 10: Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network. Cisplatin 60 /etoposide 120 in Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 15

16 TOPOTECAN (oral) (SCLC) Indication: Relapsed small cell lung cancer (second line) People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) NICE: Oral topotecan is recommended as an option only for people with relapsed small-cell lung cancer for whom re-treatment with the first-line regimen is not considered appropriate and the combination of cyclophosphamide, doxorubicin and vincristine (CAV) is contraindicated (for details of the contraindications to CAV see the summary of product characteristics for each of the component drugs). DRUG REGIMEN Days 1 to 5 Topotecan 2.3mg/m 2 orally daily Cycle Frequency: Every 3 weeks until progression DOSE MODIFICATIONS Topotecan: Renal impairment CrCl >40ml/min give 100% dose CrCl 20-39ml/min give 50% dose CrCl <20ml/min contraindicated Hepatic impairment Bilirubin <170micromol/L give 100% dose Bilirubin >170micromol/L Clinical decision Neutropenia Standard oncology practice for the management of neutropenia is either to administer topotecan with other medications (e.g. G-CSF) or to dose reduce to maintain neutrophil counts. In this clinical situation, dose reduction is usually appropriate If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 10 9 /l) for seven days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the dose should be reduced by 0.4 mg/m 2 /day to 1.9 mg/m 2 /day (or subsequently down to 1.5 mg/m 2 /day if necessary). Topotecan oral Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 16

17 INVESTIGATIONS Routine Blood test 1) Blood results required before drug administration Give Discuss Hb x g/dl 9 < 9 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < st treatment, <1.0 for subsequent treatment Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION ANTIEMETIC POLICY Low emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Febrile neutropenia Interstitial lung disease Diarrhoea - may be severe and on occasion associated with neutropenic colitis. It should be managed aggressively with anti-diarrhoeals, antibiotics, maintenance of hydration and admission if required. REFERENCES 1. NICE TA 184 November SPC November 2010 Topotecan oral Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 17

18 AFATINIB (NSCLC) Indication: Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation-positive locally advanced or metastatic Non Small Cell Lung Cancer where the person has not previously had an EGFR-TK inhibitor NICE TA310 Afatinib is recommended as a possible treatment for adults with locally advanced or metastatic non-small-cell lung cancer if: their cancer tests positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and they have not had a type of drug called an EGFR-TK inhibitor before DRUG REGIMEN Day 1 Afatinib 40mg orally daily (may be escalated to 50mg/daily) Cycle Frequency: Until disease progression or unacceptable toxicity. Review every 2 months by CT scan DOSE MODIFICATIONS If dose reduction required reduce dose by 10mg increments to 20mg Afatinib: Renal impairment Severe renal impairment (CrCl <30ml/min) not recommended. Hepatic impairment Exposure to afatinib is not significantly changed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Adjustments to the starting dose are not necessary in patients with mild or moderate hepatic impairment. This medicinal product has not been studied in patients with severe (Child Pugh C) hepatic impairment. Treatment in this population is not recommended Afatinib Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 18

19 INVESTIGATIONS Routine Blood test 1) Blood results required before drug administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Take one hour before or two hours after meals. Some of the following may be required for treatment of the skin rash: E45 / Diprobase, Hydrocortisone 1%/2.5%, Clindamycin gel 1%, Oxytetracycline 500mg po bd (for 2 weeks) Prednisolone 25mg po od for 7 days then reducing by 5mg per day to stop. ANTIEMETIC POLICY Minimal emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Skin rash initial rash may be severe. Diarrhoea Proactive management of diarrhoea including adequate hydration combined with antidiarrhoeal medicinal products especially within the first 6 weeks of the treatment is important and should start at first signs of diarrhoea. REFERENCES Afatinib Named Patient Use ( ) Information Pack Sept 2011 SPC June 2014 Afatinib Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 19

20 ALECTINIB (NSCLC) Alectinib for untreated anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer where the following criteria are met: 2. The patient has a histologically or cytologically confirmed diagnosis of stage IIIB or IV non small cell lung cancer that carries an anaplastic lymphoma kinase (ALK) rearrangement 3. The patient has received no previous ALK-targeted therapy 4. The patient has received no previous cytotoxic chemotherapy for locally advanced or metastatic non small cell lung cancer ie no previous systemic treatment except when this has been given as neoadjuvant or adjuvant therapy or concurrently with radiotherapy 5. Alectinib will be used only as single-agent therapy 6. The patient has an ECOG performance status of 0 or 1 or 2 7. The patient either has no brain metastases or, if the patient has brain metastases, the patient is symptomatically stable prior to starting alectinib 8. The patient will be treated until loss of clinical benefit or excessive toxicity or patient choice to discontinue treatment, whichever is the sooner 9. Treatment breaks of up to 6 weeks are allowed but solely to allow toxicities to settle 10. Alectinib will be otherwise used as set out in its Summary of Product Characteristics 11. In cases of intolerance to alectinib, either ceritinib or crizotinib is to be used only if the patient has not had progressive disease whilst on alectinib. Neither ceritinib nor crizotinib are to be used following disease progression on alectinib as there is no current clear evidence to support treatment with ceritinib or crizotinib after disease progression on alectinib. Alectinib cannot be used in any line other than 1st line as the manufacturer chose not to make a submission to NICE for its licensed indication for use after crizotinib DRUG REGIMEN Day 1 Alectinib 60mg orally twice daily Cycle Frequency: Until disease progression or unacceptable toxicity. Review every 2 months by CT scan DOSE MODIFICATIONS If dose reduction required reduce dose by 10mg increments to 20mg Alectinib: Dose reduction schedule Starting dose First dose reduction Second dose reduction Dose level 600 mg twice daily 450 mg twice daily 300 mg twice daily Alectinib Page 1 of 3 Published: January 2019 Chemotherapy regimens Lung Cancer 20

21 Dose modification advice for specified Adverse Drug Reactions CTCAE grade Alecetinib treatment ILD/pneumonitis of any severity grade Immediately interrupt and permanently discontinue Alecetinib if no other potential causes of ILD/pneumonitis have been identified. ALT or AST elevation of Grade 3 Temporarily withhold until recovery to baseline (> 5 times ULN) with total or Grade 1 ( 3 times ULN), then resume at bilirubin 2 times ULN reduced dose ALT or AST elevation of Grade 2 (> 3 times ULN) with total bilirubin elevation > 2 times ULN in the absence of cholestasis or haemolysis Permanently discontinue Alecetinib Bradycardia Grade 2 or Grade 3 Temporarily withhold until recovery to Grade 1 (symptomatic, may be severe and (asymptomatic) bradycardia or to a heart rate of medically significant, medical 60 bpm. Evaluate concomitant medicinal products intervention indicated) known to cause bradycardia, as well as anti-hypertensive medicinal products. If a contributing concomitant medicinal product is identified and discontinued, or its dose is adjusted, resume at previous dose upon recovery to Grade 1 (asymptomatic) bradycardia or to a heart rate of 60bpm. If no contributing concomitant medicinal product is identified, or if contributing concomitant medicinal products are not discontinued or dose modified, resume at reduced dose upon recovery to Grade 1 (asymptomatic) bradycardia or to a heart rate of 60bpm. Bradycardia Grade 4 (life-threatening consequences, urgent intervention indicated) CPK elevation > 5 times ULN CPK elevation > 10 times ULN or second occurrence of CPK elevation of > 5 times ULN Permanently discontinue if no contributing concomitant medicinal product is identified. If a contributing medicinal product is identified and discontinued, or its dose is adjusted, resume at reduced dose upon recovery to Grade 1 (asymptomatic) bradycardia or to a heart rate of 60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue in case of recurrence. Temporarily withhold until recovery to baseline or to 2.5 times ULN, then resume at the same dose. Temporarily withhold until recovery to baseline or to 2.5 times ULN, then resume at reduced dose Alectinib Page 2 of 3 Published: January 2019 Chemotherapy regimens Lung Cancer 21

22 Hepatic impairment No dose adjustment is required in patients with mild hepatic impairment. Alecensa has not been studied in patients with moderate to severe hepatic impairment. Therefore, Alecensa is not recommended in patients with moderate to severe hepatic impairment (see section 5.2). Also see SPC Renal impairment No dose adjustment is required in patients with mild or moderate renal impairment. Alecensa has not been studied in patients with severe renal impairment. However, since alectinib elimination via the kidney is negligible, no dose adjustment is required in patients with severe renal impairment (see section 5.2). INVESTIGATIONS Liver function, including ALT, AST, and total bilirubin should be monitored at baseline and then every 2 weeks during the first 3 months of treatment. Thereafter, monitoring should be performed periodically, Blood tests should initially be performed as clinically indicated. FBC Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION ANTIEMETIC POLICY Minimal emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Interstitial lung disease / pneumonitis Hepatotoxicity Bradycardia Severe myalgia GI effects REFERENCES EAMS letter 1/9/17 SPC July 2017 NICE TA310 April 2014 SPC 20.Jan CDF 28/6/18 Alectinib Page 3 of 3 Published: January 2019 Chemotherapy regimens Lung Cancer 22

23 ATEZOLIZUMAB (NSCLC) Indications: Atezolizumab for treating previously platinum-treated locally advanced/ metastatic non squamous or squamous non-small cell lung cancer which has been prospectively determined before this application to be PD-L1 positive or PD-L1 negative or PD-L1 unquantifiable at PD-L1 assay or one in which PD-L1 status cannot be determined on account of insufficient lung cancer tissue being available for PD-L1 assay 2. The prescribing clinician is fully aware of the management of and the treatment modifications that may be required for immune-related adverse reactions due to anti-pd-l1 treatments including pneumonitis, colitis, nephritis, endocrinopathies and hepatitis. 3. The patient has a histologically- or cytologically-confirmed diagnosis of stage IIIB or IV non-small cell lung cancer and is either non-squamous or squamous in type. 4. The patient has either progressed after previously receiving at least 2 cycles of platinumcontaining chemotherapy for stage IIIB or IV non-small cell lung cancer and also a targeted treatment if the tumour is EGFR positive or ALK positive or progressed within 6 months of completing platinum-based chemotherapy given as adjuvant or neoadjuvant therapy or concurrent with radiotherapy 5. PD-L1 testing with an approved and validated test to determine the Tumour Proportion Score (TPS) has been attempted prior to this application. Either:- The TPS score will be documented- The TPS score cannot be documented as the TPS result was unquantifiable - PD-L1 testing was not possible as the pathologist has documented that there is insufficient tissue for PD-L1 analysis 6. The patient has a performance status (PS) of 0 or 1 and would otherwise be potentially fit for docetaxel-based 2nd line chemotherapy 7. The patient has no symptomatically active brain metastases or leptomeningeal metastases. 8. Atezolizumab will be administered as monotherapy 9. The patient has not received prior treatment with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody 10. Atezolizumab will be stopped at 2 years of treatment or on loss of clinical benefit or unacceptable toxicity, whichever occurs first. 11. A formal medical review as to whether treatment with atezolizumab should continue or not will be scheduled to occur at least by the end of the first 9 weeks of treatment 12. Treatment breaks of up to 12 weeks beyond the expected cycle length of atezolizumab are allowed solely to allow immune toxicities to settle 13. Atezolizumab will otherwise be used as set out in SPC with the exception of criteria 10 DRUG REGIMEN Day 1 Atezolizumab 1200mg in 250ml sodium chloride 0.9% IV infusion Cycle Frequency: every 3 weeks until disease progression to a maximum 2 years Atezolizumab Page 1 of 5 Published: January 2019 Chemotherapy regimens Lung Cancer 23

24 DOSE MODIFICATIONS Dose modification advice for specified adverse drug reactions Pneumonitis Grade 2 Grade 3 or 4 Withhold Atezolizumab Treatment may be resumed when the event improves to Grade 0 or Grade 1 within 12 weeks, and corticosteroids have been reduced to 10 mg prednisone or equivalent per day Permanently discontinue Atezolizumab Hepatitis Grade 2: Withhold Atezolizumab (ALT or AST > 3 to Treatment may be resumed when the event improves to Grade 0 or 5 x [ULN]x x ULN Grade 1 within 12 weeks and corticosteroids have been reduced to or blood or bilirubin > mg prednisone or equivalent per day to 3 x ULN) Grade 3 or 4: (ALT or AST > 5 x ULN or blood bilirubin > 3 x ULN) Permanently discontinue Atezolizumab Colitis Grade 2 or 3 Diarrhoea Withhold Atezolizumab (increase of 4 Treatment may be resumed when the event improves to Grade 0 or stools/day over baseline) Grade 1 within 12 weeks and corticosteroids have been reduced to or Symptomatic Colitis 10 mg prednisone equivalent per day Grade 4 Diarrhoea or Permanently discontinue Atezolizumab Colitis (life threatening; urgent intervention indicated) Hypothyroidism or hyperthyroidism Symptomatic Withhold Atezolizumab Hypothyroidism: Treatment may be resumed when symptoms are controlled by thyroid replacement therapy and TSH levels are decreasing Hyperthyroidism: Treatment may be resumed when symptoms are controlled by antithyroid medicinal product and thyroid function is improving Atezolizumab Page 2 of 5 Published: January 2019 Chemotherapy regimens Lung Cancer 24

25 Adrenal insufficiency Symptomatic Withhold Atezolizumab Treatment may be resumed when the symptoms improve to Grade 0 or Grade 1 within 12 weeks and corticosteroids have been reduced to 10 mg prednisone or equivalent per day and patient is stable on replacement therapy Hypophysitis Grade 2 or 3 Grade 4 Withhold Atezolizumab Treatment may be resumed when the symptoms improve to Grade 0 or Grade 1 within 12 weeks and corticosteroids have been reduced to 10 mg prednisone or equivalent per day and patient is stable on replacement therapy Permanently discontinue Atezolizumab Type 1 diabetes mellitus Grade 3 or 4 hyperglycaemia (fasting glucose > 250 mg/dl or 13.9 mmol/l) Withhold Atezolizumab Treatment may be resumed when metabolic control is achieved on insulin replacement therapy Infusion-related reactions Grade 1 or 2 Reduce infusion rate or interrupt. Treatment may be resumed when the event is resolved Grade 3 or 4 Rash Grade 3 Grade 4 Permanently discontinue Atezolizumab Withhold Atezolizumab Treatment may be resumed when rash is resolved and corticosteroids have been reduced to 10 mg prednisone or equivalent per day Permanently discontinue Atezolizumab Myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome and Meningoencephalitis All Grades Permanently discontinue Atezolizumab Atezolizumab Page 3 of 5 Published: January 2019 Chemotherapy regimens Lung Cancer 25

26 Pancreatitis Grade 3 or 4 serum amylase or lipase levels increased (> 2 x ULN) or Grade 2 or 3 pancreatitis Grade 4 or any grade of recurrent pancreatitis Withhold Atezolizumab Treatment may be resumed when serum amylase and lipase levels improve to Grade 0 or Grade 1 within 12 weeks, or symptoms of pancreatitis have resolved, and corticosteroids have been reduced to 10 mg prednisone or equivalent per day Permanently discontinue Atezolizumab Atezolizumab should be permanently discontinued: For Grade 4 toxicities except for endocrinopathies that are controlled with replacement hormones For any recurrent event at Grade 3 severity If a treatment-related toxicity does not resolve to Grade 0 or Grade 1 within 12 weeks after adverse reaction onset date If a corticosteroid dose of > 10 mg prednisone or equivalent per day is required for treatmentrelated toxicity beyond 12 weeks after adverse reaction onset date. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) 2) Non-urgent tests Tests relating to disease response/progression CONCURRENT MEDICATION None required ANTI-EMETIC POLICY Low emetic risk Atezolizumab Page 4 of 5 Published: January 2019 Chemotherapy regimens Lung Cancer 26

27 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS inflammation of the lung (pneumonitis): symptoms may include new or worsening cough, shortness of breath, and chest pain inflammation of the liver (hepatitis): symptoms may include yellowing of skin or eyes, nausea, vomiting, bleeding or bruising, dark urine, and stomach pain inflammation of the intestines (colitis): symptoms may include diarrhoea (watery, loose or soft stools), blood in stools, and stomach pain inflammation of the thyroid and adrenal glands (hypo-thyroidism, hyper-thyroidism, or adrenal insufficiency): symptoms may include tiredness, weight loss, weight gain, change in mood, hair loss, constipation, and dizziness type 1 diabetes mellitus, including acid in the blood produced from diabetes (diabetic ketoacidosis): symptoms may include feeling more hungry or thirsty than usual, need to urinate more often, weight loss, and feeling tired inflammation of the brain (encephalitis) or inflammation of the membrane around the spinal cord and brain (meningitis): symptoms may include neck stiffness, headache, fever, chills, vomiting, eye sensitivity to light, confusion and sleepiness inflammation or problems of the nerves (neuropathy): symptoms may include muscle weakness and numbness, tingling in hands and feet inflammation of the pancreas (pancreatitis): symptoms may include abdominal pain, nausea and vomiting severe reactions associated with infusion (events occurring during or within one day of having the infusion) may include fever, chills, shortness of breath and flushing. REFERENCES SPC Atezolizumab Page 5 of 5 Published: January 2019 Chemotherapy regimens Lung Cancer 27

28 CERITINIB (NSCLC) Indication: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. The first line treatment of anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer 2. The patient has a histologically or cytologically confirmed diagnosis of stage IIIB or IV non small cell lung cancer that carries an anaplastic lymphoma kinase (ALK) rearrangement 3. The patient has received no previous ALK-targeted therapy 4. The patient has received no previous cytotoxic chemotherapy for locally advanced or metastatic non small cell lung cancer ie no previous systemic treatment except when this has been given as neoadjuvant or adjuvant therapy or concurrently with radiotherapy 5. Ceritinib will be used only as single-agent therapy 6. The patient has an ECOG performance status of 0 or 1 or 2 7. The patient either has no brain metastases or, if the patient has brain metastases, the patient is symptomatically stable prior to starting ceritinib 8. The patient will be treated until loss of clinical benefit or excessive toxicity or patient choice to discontinue treatment, whichever is the sooner 9. Treatment breaks of up to 6 weeks are allowed but solely to allow toxicities to settle 10. Ceritinib will be otherwise used as set out in its Summary of Product Characteristics 11. Crizotinib is to be used only if the patient cannot tolerate ceritinib and has not had progressive disease whilst on ceritinib. Crizotinib is not to be used following disease progression on ceritinib as there is no current clear evidence to support treatment with crizotinib after disease progression on ceritinib NICE TA395 Ceritinib is recommended, within its marketing authorisation, as an option for treating advanced anaplastic lymphoma kinase positive non-small-cell lung cancer in adults who have previously had crizotinib. The drug is recommended only if the company provides it with the discount agreed in the patient access scheme. DRUG REGIMEN Day 1 Ceritinib 450mg orally daily (with or after food) Cycle Frequency: Until disease progression or unacceptable toxicity. Review every 2 months by CT scan Ceritinib Page 1 of 3 Published: January 2019 Chemotherapy regimens Lung Cancer 28

29 DOSE MODIFICATIONS Dose Interruption, Reduction, or Discontinuation Recommendations ALT or AST elevation greater than 5 times ULN with total bilirubin elevation less than or equal to 2 times ULN Withhold until recovery to baseline or less than or equal to 3 times ULN, then resume ceritinib with a 150mg dose reduction. ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysis Permanently discontinue ceritinib. Any Grade treatment-related ILD/pneumonitis Permanently discontinue ceritinib. QTc interval greater than 500 msec on at least 2 separate ECGs Withhold until QTc interval is less than 481 msec or recovery to baseline if baseline QTc is greater than or equal to 481 msec, then resume ceritinib with a 150mg dose reduction. QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia Permanently discontinue ceritinib. Severe or intolerable nausea, vomiting or diarrhea despite optimal anti-emetic or antidiarrheal therapy Withhold until improved, then resume ceritinib. with a 150mg dose reduction. Persistent hyperglycemia greater than 250 mg/dl despite optimal anti-hyperglycemic therapy Withhold until hyperglycemia is adequately controlled, then resume ceritinib with a 150mg dose reduction. If adequate hyperglycemic control cannot be achieved with optimal medical management, discontinue ceritinib. Symptomatic bradycardia that is not life-threatening Withhold until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, evaluate concomitant medications known to cause bradycardia, and adjust the dose of ceritinib. Clinically significant bradycardia requiring intervention or life-threatening bradycardia in patients taking a concomitant medication also known to cause bradycardia or a medication known to cause hypotension Withhold until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If the concomitant medication can be adjusted or discontinued, resume ceritinib. with a 150mg dose reduction, with frequent monitoring. Life-threatening bradycardia in patients who are not taking a concomitant medication also known to cause bradycardia or known to cause hypotension Permanently discontinue ceritinib.. Dose Modification for Strong CYP3A4 Inhibitors Avoid concurrent use of strong CYP3A inhibitors during treatment with ceritinib If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the ceritinib dose by a pproximately one-third, rounded to the nearest 150 mg dosage strength. After discontinuation of a strong CYP3A inhibitor, resume the ceritinib dose that was taken prior to initiating the strong CYP3A4 inhibitor. Ceritinib Page 2 of 3 Published: January 2019 Chemotherapy Review: regimens January 2021 Lung Cancer 29

30 INVESTIGATIONS Pre assessment CT- chest abdomen pelvis FBC U and E's LFT's ECG Creatinine Blood tests should initially be performed monthly FBC Creatinine Liver function tests (LFT) CONCURRENT MEDICATION ANTIEMETIC POLICY Minimal emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS REFERENCES SPC September 2015 CAG January 2019January 2021 Ceritinib Page 3 of 3 Published: January 2019 Chemotherapy regimens Lung Cancer 30

31 Cisplatin (50) Etoposide (50) with RT (NSCLC) Indication: Superior sulcus non-small cell carcinoma DRUG REGIMEN Day 1, 8, 29 & 36 Pre-hydration CISPLATIN 50mg/m 2 infusion in 1000ml sodium chloride 0.9% over 2 hours Post hydration Days 1 to 5 ETOPOSIDE 50mg/m 2 infusion in 500ml* sodium chloride 0.9% over 60 minutes Days 29 to 33 ETOPOSIDE 50mg/m 2 infusion in 500ml* sodium chloride 0.9% over 60 minutes *doses 48mg to 88mg in 250ml, 96mg to 180mg in 500ml, 200mg to 360mg in 1000ml sodium chloride 0.9% This regimen is given concurrently with radiotherapy. Radiation and chemotherapy to start within 24 hours of each other. Number of cycles: 1 cycle DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Cisplatin / etoposide sulcus Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 31

32 INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN regimens. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk days 1, 8, 29 and 36 Low emetic risk days 2 to 5 and days 30 to 33 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity ensure adequate pre and post hydration is prescribed. Ototoxicity assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Rusch VW, Giroux KJ, Kraut JC et al. Induction Chemoradiation and Surgical Resection for Superior Sulcus Non-Small Cell Lung Carcinomas: Long-Term Results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol 25: , Cisplatin / etoposide sulcus Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 32

33 Cisplatin Vinorelbine with concurrent RT (NSCLC) Indication: Non-small cell lung cancer suitable for chemoradiotherapy DRUG REGIMEN Days 1 to 4 & 22 to 25 Pre-hydration CISPLATIN 20mg/m 2 infusion in 1000ml sodium chloride 0.9% over 2 hours (with fractions 1-4 and of radiotherapy) Post hydration Days 1, 8, 19 & 26 VINORELBINE 15mg/m 2 infusion in 50ml sodium chloride 0.9% over 10 minutes prior to radiotherapy on fractions 1, 6, 15, and 20 Radiotherapy should be given no more than 6 hours after starting the cisplatin Number of cycles: 1 cycle of 42 days DOSE MODIFICATIONS Haematological ANC X109/L PLATELETS X109/L VINORELBINE CISPLATIN >1.5 and > % 100% or omit 100% <1.0 or <60 omit omit Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Vinorelbine: If bilirubin > 2 x ULN or AST/ALT > 5 x ULN reduce to 66.6% Cisplatin / vinorelbine RT Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 33

34 INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN regimens. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give mg Furosemide PO/IV OR 200ml Mannitol 10% IV. Ciprofloxacin 500mg po BD days 8 to 20 and 29 to 41 ANTIEMETIC POLICY Highly emetogenic day 1-4 and Minimal emetogenic risk days 8, 19 and 26 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity ensure adequate pre and post hydration is prescribed. Ototoxicity assess patient for tinnitus or hearing abnormalities. REFERENCES SOCCAR trial Cisplatin / vinorelbine RT Page 2of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 34

35 GEMCITABINE CISPLATIN (NSCLC) Indication: Standard combination for palliative treatment of NSCLC Unknown primary if appropriate NICE guidance Docetaxel, gemcitabine, paclitaxel and vinorelbine should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. DRUG REGIMEN Day 1 PRE-HYDRATION GEMCITABINE 1250mg/m 2 infusion in 250ml sodium chloride 0.9% over 30 minutes CISPLATIN 80mg/m 2 infusion in 1000ml sodium chloride 0.9% over 2 hours POST-HYDRATION Day 8 GEMCITABINE 1250mg/m 2 infusion in 250ml sodium chloride 0.9% over 30 minutes Cycle Frequency: Every 21 days Number of cycles: up to 4 (subject to tolerance and response) DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Gemcitabine: CrCl <30ml/min consider dose reduction (Clinical decision) If bilirubin >27micromol/L initiate treatment with dose of 800mg/m 2 Neutrophils >1.5x10x 9 /L and platelets >100x10x 9 /L give 100% dose (Day 1 and 8) Neutrophils x10x 9 /L or platelets x10x 9 /L give 75% dose (Day 8 only) or delay based on clinical assessment (Day 1 and 8) Neutrophils <0.5x10x 9 /L or platelets <50x10x 9 /L delay treatment (Day 1) or omit treatment (Day 8). Diarrhoea and/or mucositis Grade 2 toxicity omit until toxicity resolved then restart at 100% dose Grade 3 toxicity omit until toxicity resolved then restart at 75% dose Grade 4 toxicity omit until toxicity resolved then restart at 50% dose Omit if treatment is delayed for more than 4 weeks but continue with Cisplatin Cisplatin / Gemcitabine Page 1 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 35

36 INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dl 10 < 10 Plt x 10 9 /L 100 < 100 Neutrophils x 10 9 /L 1.5 < 1.5 Liver function tests (LFT) Creatinine clearance (GFR) calculated OR EDTA at the Consultants discretion (Cisplatin). 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN regimens. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk day 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity ensure adequate pre and post hydration is prescribed. Ototoxicity assess patient for tinnitus or hearing abnormalities. Diarrhoea see dose modifications treat with loperamide or codeine. Mucositis see dose modifications use routine mouth care. REFERENCES 1. Giaccone G et al. Seminars in Oncology 2002; 29 (3) Supp 9: Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network. Cisplatin / Gemcitabine Page 2 of 2 Published: January 2019 Chemotherapy regimens Lung Cancer 36