Βασικές αρχές χηµειοθεραπείας στην αντιµετώπιση του µικροκυτταρικού καρκίνου (SCLC)

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1 Βασικές αρχές χηµειοθεραπείας στην αντιµετώπιση του µικροκυτταρικού καρκίνου (SCLC) Δηµήτρης Διονυσόπουλος MD, PhD Ειδικός Παθολόγος Ογκολόγος Επιµελητής Β Γ.Ν. Παπαγεωργίου Απρίλιος 2014

2 Progress in the therapy of SCLC has been painfully slow. In fact you could argue that little or no therapeutic advances have been made for extensive- stage SCLC in more than 20 years. Gandara and Lara. J Clin Oncol 2008

3 ΔΕΔΟΜΕΝΑ ü Η συχνότητα µειώνεται µε το χρόνο (από17.26% το 1986 στο 12.95% το 2002 των περιπτώσεων καρκίνου του πνεύµονα στις ΗΠΑ (Govindan JCO 2006) ü Το 1/3 των ασθενών έχουν περιορισµένη νόσο ü Εξαιρετική χηµειοευαίσθητη και ακτινοευαίσθητη νόσος ü Λίγοι ασθενείς έχουν µακρά επιβίωση ü Υψηλός κίνδυνος τοπικής υποτροπής ü Υψηλός κίνδυνος µεταστάσεων (εγκέφαλος)

limited-stage SCLC stage I to III (T any, N any, M0) that can be safely treated with definitive radiation therapy; Extensive-stage SCLC stage IV (T any, N any, M1a/b) or T3 4 due to multiple lung

4 limited-stage SCLC stage I to III (T any, N any, M0) that can be safely treated with definitive radiation therapy; Extensive-stage SCLC stage IV (T any, N any, M1a/b) or T3 4 due to multiple lung nodules or tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Because of the aggressive nature of SCLC, staging should not delay the onset of treatment for more than 1 week

5 State of the art treatment of SCLC ØPlatinum-based combination chemotherapy (PE) at full standard doses, x 4-6 as 1st line treatment for both LD and ED patients. ØEarly thoracic irradiation (TRT), Gy, added to CT for LD patients. ØProphylactic cranial irradiation (PCI), Gy, for patients with either LD or ED and CR/good PR. ØSingle agent CT (Topotecan) as 2nd line treatment for relapsed SCLC. A Ardizzoni, ASCO 2007

6 CEVcyclophosphamide/epirubicin/vincristine EPetoposide/cisplatin EP 436 patients with LS and ES EP vs CEV Survival 10.2 vs 7.8 p = CEV Sundstrøm et al. J Clin Oncol 2002

7 Overall survival LSD 14.5m vs 9.7m p = 0.01 Overall survival ESD 8.4m vs 6.5m p = ns

8 Platinum vs non-platinum 21 phase III trials extensive stage SCLC ü between 1972 and 1990 ü median survival 9.5 vs 7.1 months, p = ü cisplatin based therapy independent predictor of survival p = 0.04 Chute et al, J Clin Oncol 1999 Meta-analysis 19 trials 4054 pts ü cisplatin vs no cisplatin ü Cisplatin - 4.4% survival benefit at 1 year Pujol et al Br J Cancer 2000 Cochrane meta-analysis 2008 ü 29 trials, 5530 patients ü No difference in 6, 12 or 24 month survival ü No difference OR rate ü Higher CR rate for platinum ü Higher toxicity rates with platinum Amarasena et al. Cochrane Library 2009

10 EXPECTATIONS In pts with limited-stage disease, response rates of 70% to 90% are expected after treatment with EP plus thoracic RT, whereas in extensive-stage disease, response rates of 60% to 70% can be achieved with combination chemotherapy alone. Unfortunately, median survival rates are only 14 to 20 months and 9 to 11 months for pts with limited- and extensive-stage disease, respectively. After appropriate treatment, the 2-year survival rate is approximately 40% in pts with limited-stage disease, but less than 5% in those with extensive-stage disease

11 OTHER STRATEGIES üplatinum + Irinotecan ütriplets (addition of paclitaxel) ümaintenance / Consolidation chemo üalternating / Sequential regimens ühigher doses of standard chemotherapy üantiangiogenic agents (bevacizumab)

12 Algorithm of first-line treatment for limited disease SCLC1,2 Very limited disease (T1 3, N0 1) Limited disease Surgery Combination chemotherapy (4 6 cycles) based on etoposide platinum or cyclophosphamide doxorubicin Thoracic radiotherapy Start in cycle 1 or 2 during chemotherapy Prophylactic brain irradiation in all patients with CR Figure modified from: 1. Felip E et al. Ann Oncol 2005; 16(S1): i30 i Jackman DM, Johnson BE. Lancet 2005; 366:

13 SCLC PS 0-2 chemo + concurrent XRT Limited stage PS 3-4 Due to SCLC chemo+ - XRT PS 3-4 Individualized treatment not due to SCLC BSC

14 Algorithm of first-line treatment for extensive disease SCLC Extensive disease Combination chemotherapy (4 6 cycles) based on etoposide platinum Thoracic radiotherapy in patients with CR or PR Additional chemotherapy for progressive or recurrent disease Prophylactic brain irradiation in all patients with CR SCLC; small cell lung cancer; CR: complete response; PR: partial response Figure modified from: Jackman DM, Johnson BE. Lancet 2005; 366:

15 Treatment paradigm for relapsed SCLC1,2 Relapsed disease median survival only 4 to 5 months NO YES Refractory Resistant TFI <90 days Sensitive TFI 90 days BSC or active treatment Non-cross resistant chemotherapy Re-challenge first-line or other chemotherapy regimen SCLC: small cell lung cancer; TFI: treatment-free interval; BSC: best supportive care Figure modified from: 1. Cheng S et al. J Thorac Oncol 2007; 2(4): Ferraldeschi R et al. Drugs 2007; 67(15):

16 RELAPSED DISEASE Based on phase II trials, active subsequent agents include ü paclitaxel, ü docetaxel, ü topotecan, ü irinotecan, ü vinorelbine, ü gemcitabine, ü ifosfamide, ü temozolomide, and ü oral etoposide

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