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Chemotherapy and Radiotherapy in the Palliative Care of Cancer Patients

Chemotherapy and Radiotherapy in the Palliative Care of Cancer Patients. Palliation is - to alleviate the symptoms of disease without curing it. Palliation. By definition palliative treatment must be as harmless as possible. “the cure cannot be worse than the disease”

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Chemotherapy and Radiotherapy in the Palliative Care of Cancer Patients

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  1. Chemotherapy and Radiotherapy in the Palliative Care of Cancer Patients M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  2. Palliation is - to alleviate the symptoms of disease without curing it M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  3. Palliation • By definition palliative treatment must be as harmless as possible. • “the cure cannot be worse than the disease” • Palliative radiotherapy has been used for many years • Palliative chemotherapy has only recently been regularly applied M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  4. Palliative Radiotherapy • Pain relief • Bone metastases • Soft tissue metastases • Obstruction • Bronchial • Bowel • Nerves (spinal cord, brachial plexus) • Brain metastases M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  5. Palliative radiation and patient expectations Chow Clin Oncol 2001 • Canadian study - 60 patients • 20% expected cancer cure from palliative XRT • 38% expected prolongation of life M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  6. Palliative xrt - bone metastases • dose regimens • 30 Gy/ 10 fx/ 2 w • 20 Gy/ 5 fx/ 4 w • 8-10 Gy/ 1 fx • short treatment schemes result in quicker response but of shorter duration M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  7. Bone metastases - XRT dose • Royal Marsden study • *8 Gy x 1 v 3 Gy x 10 (2 weeks) • no difference • Edinburgh Study • 10 Gy x 1 v 4.5 Gy x 5 • RR 84% v 89% • CR 39% v 42% • duration 13.5 w v 14 w M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  8. Bone Metastases survival following radiotherapy M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  9. Bone metastases - policy prognosis # of lesions protocol • Excellent single 60 Gy in 5 w • Good 1-3 30 Gy in 2 w • Good multiple large field 30 Gy • Poor 1-3 single 10 Gy • Poor multiple half body XRT M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  10. Palliative xrt - bone metastases treatment planning • good margins • e.g. add 1-2 vertebrae on each side • include nearby asymptomatic lesions • avoid irradiating entire limb circumference • reduce irradiated volume of bowel/bladder • bone marrow toxicity M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  11. Palliative xrt -single fraction half body iradiation • lower half body 8 Gy • upper half body 6 Gy • good short term palliation (~3 months) • onset of pain relief • Half Body xrt 50% @ 3 days, 100% @ 14 days • Focal XRT 50% @ 14 days, 80% @ 14 days • Salazar Cancer 1986 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  12. Palliative xrt -single fraction half body iradiation • half body XRT only recommended for widespread bony metastases • Soft tissue lesions are better treated with planned focal radiotherapy (less toxicity) M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  13. Lung cancer –presentation • Most patients with lung cancer present with advanced disease or develop symptomatic metastases at a later stage • These patients usually need palliative radiation or chemotherapy M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  14. Lung cancer - palliative xrt • Treatment of symptoms • Pain • Cough • Dyspnea • Hemoptysis • Dysphagia • Post-obstructive pneumonia • SVC syndrome M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  15. Results of Palliative Radiotherapy for Non-small Cell Lung Cancer • Arm/shoulder pain 73% • Chest pain 50-80% • Cough 50-65% • Dyspnea 37-60% • Hemoptysis 76-95% • Atelectasis 23% • Svc syndrome 86% • Vocal cord paralysis 6% M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  16. Results of Palliative Radiotherapy for Non-small Cell Lung Cancer • Pain 78% • Cough 60% • Dyspnea 61% • Hemoptysis 84% • Anorexia 67% • Objective response 30% MRC study Br J Cancer 63:335-342, 1991 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  17. Lung Cancer XRT -Toxicity • esophagitis • fatigue • cough • dyspnea/pneumonitis/fibrosis • hematological • spinal cord • cardiac M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  18. Palliative lung xrt techniques • Encompass whole tumor • Minimize extra lung volume • Include mediastinal nodes only if close (i.e. central tumor) • Dose, Volume, Fractionation depend on • Patient’s general state • age • comorbid disease • chemotherapy M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  19. Impact of virtual simulation on palliative lung radiotherapy • CT based planning and DRRs matched with simulator planned fields • Complete match 5% • Major mis-match 66% • Conventional simulation larger 82% • Mean target under-coverage 16.5% • Mean normal tissue over-coverage 25.5% M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  20. Lung cancer palliative radiation - dose schemes • 40 Gy/ 20 fx/ 4 weeks • 30 Gy/ 10 fx/ 2 weeks • 17 Gy/ 2 fx/ weekly • 10 Gy/ single fraction M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  21. Lung cancer - palliative xrt • stage III inop, good PS • 17 Gy/2 v 39 Gy/13 • response earlier • med dysphagia 6 d 14 d • median survival 7 mo 9 mo • 2 yr survival 9% 12% M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  22. Palliative Endobronchial Brachytherapy • High Dose Rate v Low Dose Rate • endobronchial disease • Advantages of HDR • Short treatment time (15-30 minutes v 12-24 hours) • Outpatient procedure • Computerized dose planning M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  23. Palliative Endobronchial Brachytherapy • subjective responses • dyspnea 64-100% • cough 30-93% • hemoptysis 50-100% • pneumonitis/ atelectasis 66-100% • median response duration 7.5 months • lifetime symptom free recurrence 50% • toxicity (tumor related?) • hemoptysis (5-15%) • fistula M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  24. Lung cancer palliation: external beam v intraluminal brachytherapy STOUT 2000 HDR brachytherapyExternal beam 15Gy @ 1cm 30 Gy in 8 fx Dysphagia 45% 85% Cough relief 50% 67% Chest pain relief 43% 77% Good palliation (MD) 76% 91% Good palliation (patient) 59% 83% Median survival 250d 287d M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  25. Liver Metastases radiotherapy - RTOG studies • 21 Gy in 7 fractions / 10 days (+/- misonidazole) • equivalent to 30 Gy / 10 fx / 2 weeks • 187 patients evaluable • Karnofsky increase by 10 points 28% • by 20 points 11% • pain relief 80% (complete 55%) • median survival 4 months • Leibel IJROBP 1987 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  26. Palliative xrt -single fraction half body iradiation • lower half body 8 Gy • upper half body 6 Gy • good short term palliation (~3 months) M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  27. Brain metastases • Brain metastases are often multifocal requiring whole brain irradiation • Patients with few (<3) metastases may benefit from stereotactic radiosurgery particularly if primary is radioresistant (e.g. melanoma or renal cell carcinoma) M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  28. Principles of palliative radiotherapy 1 • Examine patient and listen to complaints. • Treat patient’s symptoms, not his imaging. • Palliative radiotherapy often requires more individualized treatment and attention to detail than curative radiotherapy (which is given per protocol). M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  29. Principles of palliative radiotherapy 2 • Avoid unnecessary treatment of large volumes. • Avoid prolonging treatment over many sessions. • Simulation and careful planning are needed even for single large dose treatment. M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  30. Palliative chemotherapy • The use of nitrogen mustards in the palliative treatment of carcinoma with particular reference to bronchogenic carcinoma. • sKarnofsky Cancer 1:634-656 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  31. Palliative chemotherapy • Newer less toxic drugs • toxicity prevention • 5HT3 antagonists +/- dexamethasone • Prior to 5HT3 antagonists cisplatin would not have been considered appropriate for palliative care • Schedule dependent toxicity profile • Continuous infusion 5FU/ LV • Weekly topotecan • Weekly taxol M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  32. Palliative chemotherapy • Less toxic derivatives • Carboplatin v Cisplatin • Equivalent in ovarian cancer • Less effective in testicular, head & neck, bladder cancer • Newer anthracyclines • Less alopecia (cardiotoxicity not relevant) • Oral fluoropyrimidines • Tegafur + uracil • Tegafur + oxonic acid (S1) • Capecitabine • Oral etoposide M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  33. Advanced Colo-rectal cancer • Scheithauer BMJ 306:752-5, 1993 • 5FU/LV & cDDP v best supportive care • 36 pts • Longer survival • QOL scores improved M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  34. Advanced Colo-rectal cancer Cochrane meta-analysis BMJ Sept 2000 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  35. Advanced Colo-rectal cancer Cochrane meta-analysis BMJ Sept 2000 • Chemotherapy v supportive care • Quality of life • Various instruments • 3/6 studies treatment arm better • 2/6 no difference • 1/6 treatment arm worse (ineffective chemotherapy) Inadequate data to draw conclusions, Response may be surrogate for QOL M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  36. Advanced Colo-rectal cancer • Nordic study JCO 10:904-911, 1992 • 5FU & MTX Immediate v when symptomatic • Symptom-free survival 10m v 2m • Median survival 14m v 9m • Patients with objective responders and patients with stable disease benefited symptomatically M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  37. Breast cancer • Hormone therapy often preferred for advanced disease • Unethical to conduct studies of chemotherapy v BSC • Ramirez Br J Cancer 78:1488-94, 1988 • Do pts with advanced breast cancer benefit from chemotherapy M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  38. Breast cancer • Tannock JCO 6:1377-1387, 1998 • Standard dose CMF v low dose CMF • Increased chemotherapy side-effects • Nausea & vomiting, myelosupression • But improved QOL with higher CMF dose • Fraser Br J Cancer 67:402-406, 1993 • CMF v low dose Epirubicin QOL study • Better QOL with CMF M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  39. Breast cancer continuous v intermittent chemotherapy • Metastatic disease • AC or CMFP • Continuous until Progression or 3 cycles then break until progression • Linear analog scale, well-being, mood, pain, appetite, and QOL index • Continuous Rx better scores for mood, appetite, and QOL • Continuous Rx trend to longer survival • Coates NEJM 1987 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  40. Small cell lung cancer • Earl Br J Cancer 64:566, 1991 • planned v “as required” chemotherapy • Patient recorded diary cards • planned - increased chemotherapy side-effects • - less disturbance in daily activity • - better overall wellbeing • Improved QOL with planned chemotherapy M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  41. Small cell lung cancer • MRC study Lancet 348:563-566 • Oral VP-16 v i.v. VAC • 339 patients, stopped early • Trial stopped due to increased toxicity and lower survival in oral VP-16 arm M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  42. Pancreatic cancer • Gemcitabine • Rothenberg Ann Oncology 7:347-353, 1996 • clinical benefit response • Van Hoff Br J Cancer 78(suppl 3):9-13 • No survival benefit but QOL benefit M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  43. Non-small cell lung cancer • Non platinum regimens • Alkylating agents, vinca alkyloids etc • No survival or QOL benefit • Non-small cell lung cancer collaborative group – meta-analysis BMJ 311:899-909, 1995 • Platinum-based chemotherapy better than BSC M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  44. Non-small cell lung cancer • New drugs • Gemcitabine • Vinorelbine • Taxanes (docetaxel, paclitaxel) • Alone or in combination with cisplatin or carboplatin • Similar activity • Choice will depend on QOL M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  45. Non-small Cell Lung Cancer • Vinorelbine v BSC • Elderly lung cancer study group JNCI 91:66-72, 1999 • Improved survival and QOL • Gemcitabine v BSC • Anderson Lung Cancer 18(suppl 1) 1996 • Improved survival and QOL M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  46. Non-small Cell Lung Cancer • Symptomatic effect of chemotherapy M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  47. Advanced lung cancer • Stage IV Randomized study Cullen JCO 1999 • MMC/ Ifosfamide/CDDP v Best Supportive Care • Median survival 6.7 v 4.8 m • Change in QOL score (EORTC QLC-LC13) over 6 weeks • MIC – 0.09 • BSC + 0.20 • No long term symptomatic follow up M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  48. Expectations from palliative chemotherapy Doyle JCO Mar 2001 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  49. Palliative care in the elderly - radiotherapy • radiotherapy more often preferred in the elderly • radiotherapy toxicity is not age-dependent • elderly patients are more susceptible to complications of toxicity • require more meticulous treatment planning M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

  50. Palliative care in the elderly - chemotherapy • Chemotherapy • Effective palliation of chemosensitive tumors • Ovarian cancer, small cell lung cancer, lymphoma • Non-small cell lung cancer M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

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