Standard care plan for 1 st line palliative chemotherapy in advanced non small cell lung cancer References

Transcription

1 CHEMOTHERAPY CARE PLAN Document Title: Document Type: Subject: Approved by: Currency: Carboplatin & Gemcitabine combination chemotherapy (Lung cancer) Clinical Guideline Standard Care Plan 2 Years Review date: Author(s): Standard care plan for 1 st line palliative chemotherapy in advanced non small cell lung cancer References 1. Rudd et al (2005) Gemcitabine plus carboplatin versus mitomycin, ifosfamide and cisplatin in patients with stage IIIB or IV non small cell lung ca: a phase 3 randomised study of the London Lung cancer Group. J Clin Onoc. 23(1): Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carbplatin as 1 st line therapy in advanced non small cell cancer. Gronberg BH et al. J Clin Oncol Jul 1;27(19); Phase III trial of gemcitabine and carboplatin versus Mitimycin, ifosfamise and Cisplatin or Mitomycin, vinblastine and Cisplatin in patients with advanced non small cell Lung carcinoma. Danson S et al. Cancer Aug 1;98(3): Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol Nov 20;23(33): Gemcitabine (GEM) and carboplatin (CBDCA) versus cisplatin (CDDP) and vinblastine (VLB) in advanced non-small-cell lung cancer (NSCLC) stages III and IV: a phase III randomised trial. Grigorescu AC et al. Lung Cancer Jul;37(1): Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Zatloukal et al. Lung Cancer Sep;41(3): Filename Last modified Last printed Page 1 of 8 Agreed by (on behalf of team) 1.GemcitabineCarboplatin Protocol 27-Mar Mar-15 Fiona Blackhall

2 Patient group Advanced non small cell carcinoma of the lung Indications Stage IIIB and IV non small cell carcinoma of the lung No previous palliative chemotherapy received for NSCLC Histological type adenocarcinoma, squamous cell carcinoma or other NSCLC Adequate bone marrow reserve WCC >3 Plts > 100 Hb >10 (consider transfusion if anaemic) Adequate renal function GFR (Cockcroft-Gault) >50 ml/min ECOG PS 0 and 1 (selected cases with PS 2) Cautions Brain Metastasis Life expectancy < 8 weeks Co-morbidity preventing safe administration of chemotherapy Second malignancy excluding non melanomatous skin cancers in the past 3 years Anticipated benefit Publication N CR PR SD PD ORR mttp OS Rudd et al 206 1% 41% 37% 14% 42% 5.3mnts 10months at 1 year 40% Gronberg et al months Danson et al % 29% 33% 34% 30% 7.8months 8.4months Swedish Lung 334 2% 28% 30% 5.7months 10months Cancer Study Group Grigorescu et al 198 3% 24% % months Zatloukal % 4.75months 7.8 months Summary <5% 20-40% 30-40% ~35% 30-40% ~6 months ~9 months Expected toxicity Grades 3-4 Toxicity Rudd et al Gronberg et al. Danson et al. Swedish Lung Cancer Study Group Grigorescu et al Zatloukal et al Summary Alopecia 7% - 3% 3% 33% - <10% Neutropenia 34% 51% 50% 32% 2% % Thrombocytopenia 24% 56% 51% 48% 2% % Febrile neutropenia 8% 9% % CINV Nausea 5% Vomiting 4% 4% 11% 3% - - <10% Fatigue Toxic death 2% 1% <5% Anaemia 9% 13% 15% 5% % Page 2 of 8 27/03/2015

3 Initial investigations and work up prior to start of treatment 1.1. Diagnostic review and work up should usually include: Pathology/Cytology confirmed diagnosis of NSCLC Stage of disease determined and documented CT Abdomen/thorax Bronchoscopy/EBUS - desirable Clinical assessment and documentation of current disease related symptoms Performance status recorded Co-morbidities recorded Smoking status recorded FH recorded Concomitant medications recorded and stopped if necessary Baseline GFR/Creatinine clearance (Cockcroft-Gault). If borderline for isoptope GFR Baseline LFTs, Ca, LHD, FBC, UE Baseline CXR Baseline ECG Patient consented for aims, practicalities and toxicity of Gemcitabine & Carboplatin palliative chemotherapy Plan confirmed with consultant oncologist if 1 st seen by junior college 1.2. MDT meeting Case must have been through the relevant diagnostic MDT prior to commencing treatment. Overview of treatment programme Drugs and Starting Doses Gemcitabine 1250mg/m2 D1 and 8 Carboplatin AUC 5 D Treatment duration 4 Cycles (rarely 6) 1.4. Cycle length 21 days (3 weeks) Consider discontinuation if: Progressive disease clinically or radiologically (by RECIST criteria where possible) Life threatening toxicity attributed predominantly to chemotherapy Patient choice Significant change in end organ function i.e. decline in renal function GFR < 40ml/min Microangiopathic haemolytic anaemia Significant fall in PS (3 or 4) Page 3 of 8 27/03/2015

4 Exacerbation of co-morbid condition Additional medication 1.5. Anti-emetics Ondansetron 8mg IV bolus Dexamethasone 8mg IV bolus Metoclopromide (or equivalent) prn 1.6. Prophylaxis Consider prophylactic antibiotics if evidence of collapse/consolidation/cavitation associated with tumour or if deemed high risk for infection. Levofloxacin 500mg od D8 for 10 days Growth factor support Consider growth factor support if chemotherapy previously received or deemed particularly high risk for life threatening sepsis. (i.e. prosthetic heart valve). Ratiograstim/Filgrastim 300mg D9 for 7 days Other Consider prophylactic low molecular weight heparin (Dalteparin 5000units s/c od) if previous DVT/PE or deemed high risk of recurrent thromboembolic event. Clinical assessment - on Day 15 of each cycle D15 clinical assessment by medical team Graded documentation of toxicity Assessment of disease related symptoms Performance status recorded Physical examination/focussed examination performed Fitness for continuation of chemotherapy assessed and documented 1.8. Laboratory assessment D15 laboratory assessment FBC (neutrophils) UE LFTs LDH Ca Creatinine clearance (Cockcroft-Gault) 1.9. Tumour response assessment D15 imaging assessment CXR assess for tumour progression/response Page 4 of 8 27/03/2015

5 Dose modifications Haematology FBC D1 Neuts PLT >1.0 >100 Give full dose <1.0 <50 Defer 1 week and dose reduce to 75% Defer 1 week but clinical judgment on dose reduction FBC D8 Neuts PLT >1.0 >100 Give full dose <1.0 <100 Omit D8 Gemcitabine Biochemistry D1 or D8 Bilirubin >1,5 x ULN AST?ALT >2.5 x ULN 5 x ULN if sue to Liver metastases GFR/creatinine clearance <40ml/min Omit Omit Omit Febrile neutropenia / Neutropenic sepsis Grade 3 neutropenic sepsis (i.e. uncomplicated neutropenic sepsis requiring hospitalisation and IV Antibiotics) - dose reduce both drugs by 75%. (D1 and D8) Grade 4 (life threatening) neutropenic sepsis - consider cessation of chemotherapy. Growth factors to be considered if further episode of Grade 3 neutropenic sepsis despite dose reduction. Pros and cons of continuing chemotherapy to be carefully considered Haematologic toxicity Hb < 8.0 transfuse 2 units of packed red cells Hb 8-9 with symptoms - transfuse 2 units of packed red cells Plts < 10 or with evidence of bleeding - Transfuse platelets (1 adult dose) and dose reduce both drugs to 75% Multiple deferrals due to low counts require investigation and cessation of chemotherapy Non-haematologic toxicity Nausea/vomiting Grade 3 attempt control with enhancement of prophylactic anti-emetics regimen Grade 4 consider cessation of chemotherapy Any grade 4 toxicity must result in consideration of cessation of chemotherapy. Page 5 of 8 27/03/2015

6 Interpretation of response Tumour Assessment CXR performed on D15 of each cycle. CT abdo/thorax performed following cycle 4 if CXR adequate to assess response during treatment. CT abdo/thorax performed after 2 cycles if CXR inadequate to assess response. Consultant review on treatment Prior to starting chemotherapy At least once during treatment course (preferably at mid point) Subsequent active therapy options Consolidation palliative XRT Maintenance chemotherapy may be indicated Post treatment follow-up 3 monthly review with clinical assessment, CXR, FBC, LFTs, CA, UE, LDH More frequent review if indicated CT scan performed if clinically indicated Treatment options at progression Approved second line therapy if good PS Clinical trial if appropriate. Re-challenge with Gemcitabine/Carboplatin depending on response to 1 st line therapy and time to progression Palliative XRT for symptom control Best supportive care Other regimens/therapies on approval by DMC/Drugs and theraputics. On treatment assessments and schedule of investigations Visit number Week Visit description 1-2 Medical review OPA for initial discussion, information giving, arrange work-up investigations if necessary. Consent and prescribe chemotherapy if possible. Baseline CXR and bloods. ECG 2 (optional) -1 Medical review OPA for results of work-up investigations, complete consent, prescribe chemo cycle (day 1 cycle 1) Start cycle 1 within 2 weeks if clinically and practically possible but to be guided by clinical situation. Cycle 1 day 1 Gem/Carbo through protocol Page 6 of 8 27/03/2015

7 clinic unless review clinically indicated. Bloods. Antiemetics. 4 2 (day 8 cycle 1) Cycle 1 day 8 Gem through protocol clinic. Bloods. Antiemetics. 5 3 (day 15) OPA review, bloods and CXR. Assess for fitness for continuing chemotherapy. Prescribe cycle (day 21/day 1 cycle 2) Cycle 2 day 1 Gem/Carbo through protocol clinic. Bloods. Antiemetics. 7 5 (day 8 cycle 2) Cycle 2 day 8 Gem through protocol clinic. Bloods. Antiemetics. 8 6 (day 15) OPA review, bloods and CXR. Assess for fitness for continuing chemotherapy. Prescribe cycle 3. Consider booking CT scan if response uncertain. 9 7 (day 1 cycle 3) Cycle 3 day 1Gem/Carbo through protocol clinic. Bloods. Antiemetics (day 8 cycle 3) Cycle 3 day 8 Gem through protocol clinic. Bloods. Antiemetics (day 15) OPA review, bloods and CXR. Assess for fitness for continuing chemotherapy. Prescribe cycle 4. Book end of treatment CT scan (day 1 cycle 4) Cycle 4 day 1 Gem/carbo through protocol clinic. Bloods. Antiemetics (day 8 cycle 4) Cycle 4 day 8 Gem through protocol clinic. Bloods. Antiemetics (day 15) OPA review, bloods and CXR. Assessment and decision regarding number of cycles 4 or Follow up appointment with CT scan results, review and bloods monthly follow up OPA review, bloods and CXR. Page 7 of 8 27/03/2015

8 Appendices RECIST Criteria version 1.1 CR (complete response) = disappearance of all target lesions PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions SD (stable disease) = small changes that do not meet above criteria ECOG PERFORMANCE STATUS* Grade ECOG 0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 5 Dead Page 8 of 8 27/03/2015