Clinical Management Guideline for Small Cell Lung Cancer

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Diagnosis and Staging: Key Points 1. Ensure a CT scan that is <4 weeks old is available at the time of radical treatment of borderline lesions. 2. Arrange a CT scan of the chest, lower neck and upper abdomen with intravenous contrast medium administration early in the diagnostic pathway for all patients with suspected lung cancer potentially suitable for radical treatment. 3. Avoid relying on a CT scan of the chest as the sole investigation to stage the mediastinal lymph nodes. 4. Ensure positron emission tomography (PET)-CT scanning is available for all patients being considered for radical treatment. 5. Offer radical treatment without further Mediastinal lymph node sampling if there is no significant uptake in normal sized mediastinal lymph nodes on PET-CT scanning. 6. Evaluate PET positive mediastinal nodes by further mediastinal sampling. 7. Confirm the presence of isolated distant metastases/synchronous tumours by biopsy or further imaging in patients being considered for radical treatment. 8. Consider MRI or CT scanning of the head in patients selected for radical treatment, especially in stage III disease. 9. Evaluate patients with features suggestive of intracranial pathology by an initial CT scan of the head followed by MRI if normal or MRI as an initial test. 10. Biopsy adrenal lesions that show abnormal uptake on PET-CT scanning before radical treatment. 11. When obtaining diagnostic and staging samples consider the adequacy of these in the context of selection of patients for targeted therapy. 12. Ensure biopsy samples are taken in adequate numbers and size where there is negligible additional risk to the patient. 13. Use transbronchial needle aspiration (TBNA) and endobronchial ultrasound/endoscopic ultrasound (EBUS/EUS)-guided TBNA as an initial diagnostic and staging procedure according to findings on CT or PET-CT scans. 14. Confirm negative results obtained by TBNA and EBUS/EUS-guided TBNA by mediastinoscopy and lymph node biopsy where clinically appropriate. 15. The 7th edition of the TNM classification of lung cancer should be used for staging patients with lung cancer. 16. The IASLC international nodal map should be used in the assessment and staging of lymph node disease. British Thoracic Society Guidelines on the radical management of patients with lung cancer, Thorax, 2010;65 (Supp111) Document Control Prepared by Dr Jonathan Hicks Approved by Lung Cancer MCN & Prescribing Advisory Subgroup Issue date April 2013 Review date April 2015 Version V2 April 2013 Clinical Management Guidelines 1

Initial evaluation and Staging Encompassable in radical radiotherapy field Limited stage (Page 3) Follow Up Follow Up Please see the WoSCAN Regional Consensus Guideline Refer to BTS Guideline Page 1 Where possible, also assign TNM stage, according to AJCC Seventh Edition (2009) Not Encompassable in radical radiotherapy field Extensive Stage (Page 4) 2

Management of Limited Stage Disease 0-2 Suitable for concurrent Chemoradiotherapy CT Head 4500 cgy in 30 fractions, twice daily over 3 weeks + 4 cycles platinum/etoposide PD / SD PCI 2500 cgy In 10 fractions Relapse Second line chemo (page 5) Limited stage Not suitable for concurrent chemoradiotherapy Selected patients, at discretion of Consultant Up to 4 cycles platinum/etoposide CR / PR Relapse Thoracic XRT 4005 cgy in 15 fractions + PCI 2500 cgy in 10 fractions Cancer induced 3-4 Single agent carboplatin, or other reduced-intensity chemo No response Best supportive care / palliative radiotherapy 3

Management of Extensive Stage Disease 0-2 Up to 6 cycles Platinum +/- etoposide CR / PR Consider PCI 2000 cgy in 5 fractions + Consider thoracic XRT 3000 cgy in 10 fractions Relapse Extensive stage PD / SD Second line chemo (page 5) Cancer induced 3-4 Single agent carboplatin, or other reduced-intensity chemo (page 6) No response Best supportive care / palliative radiotherapy 4

Management of Relapsed or Progressive Disease Previous response to platinum-based chemo > 6 months ago Consider re-challenge with up to 4 cycles of platinum/etoposide* 0-2 Relapse / Progression Yes Up to 6 cycles of CAV Relapse / Progression No previous response or < 6 months since platinum-based chemo Suitable for IV chemo? 3-4 Best supportive care / palliative radiotherapy, consider reducedintensity chemo No Up to 6 cycles of oral topotecan ( *off label follow local approval process) 5

Standard Chemotherapy Regimens CISPLATIN + ETOPOSIDE CARBOPLATIN + ETOPOSIDE CAV (CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE) TOPOTECAN Cisplatin 75 mg/m 2 I.V. day 1 Etoposide 100mg/m 2 I.V. - days 1-3 (oral etoposide 200 mg/m 2 can be given instead of IV on days 2-3) Carboplatin AUC 6 I.V. day 1 Etoposide 100 mg/m 2 I.V. days 1-3 (oral etoposide 200 mg/m 2 can be given instead of IV on days 2-3) Cyclophosphamide 750 mg/m 2 I.V. day 1 Doxorubicin 40 mg/m 2 I.V. day 1 Vincristine 1.4 mg/m 2 (max. 2 mg) I.V. day 1 Oral topotecan 2.3 mg/m 2 for 3-5 days, every 3 weeks 6

Reduced Intensity Chemotherapy Regimens CARBOPLATIN + ETOPOSIDE SINGLE-AGENT CARBOPLATIN SINGLE-AGENT DOXORUBICIN Carboplatin AUC4 I.V. day 1 Etoposide 100 mg/m 2 I.V. up to 3 days per cycle (oral etoposide 200mg/m 2 can be given instead of I.V. on days 2-3) Up to 6 cycles Carboplatin AUC 5-6 I.V. day 1, every 3 weeks Up to 18 weeks Doxorubicin 75 mg/m 2 I.V. day 1, every 3 weeks Up to 18 weeks Weekly carboplatin or doxorubicin may be used in exceptional circumstances 7