LE OPZIONI TERAPEUTICHE NEL TUMORE DEL POLMONE CORSO INTERATTIVO SULLE MALATTIE RESPIRATORIE FUMO CORRELATE Modena 12 Dicembre 2003 LE OPZIONI TERAPEUTICHE NEL TUMORE DEL POLMONE Fausto Barbieri Dipartimento Oncologia ed Ematologia Policlinico di Modena Universita’ di Modena e Reggio Emilia

Carcinoma polmonare non a piccole cellule

Metastasi extratoraciche Linfonodi controlaterali NSCLC: stadiazione Linfonodi Invasione Parete toracica Metastasi extratoraciche Bronco principale Stadio 0 Schematic diagram showing examples of some tumor stages. Stage 0 (carcinoma in situ) - tumor is confined to the airway lining. Stage IA (T1 N0 M0) - tumor has spread to nearby lung tissue but has not reached the main bronchus. Stage IIB (T2 N1 M0) - tumor has reached main bronchus and local lymph nodes. Stage IIIB (T4 N3 M0) - tumor has invaded chest wall, trachea and the contralateral lymph nodes. Stage IV (T1 N0 M1) - distant metastasis present in the brain. Stadio IA Stadio IIB Stadio IIIB Linfonodi controlaterali Stadio IV

NSCLC: stadio alla diagnosi 50 25 15 10 Stadio IV stadio IIIB stadio IIIA stadio I-II

NSCLC: sopravvivenza per stadio IA IB IIA IIB IIIA IIIB IV

NSCLC: opzioni terapeutiche Stadio localizzato (I-IIIA N1) chirurgia (radioterapia se non candidato a CH) Malattia locoregionale (IIIA-IIIB selezionati) chemioterapia + radioterapia + chirurgia Malattia avanzata (IIIB-IV) chemioterapia + terapia supporto For localized tumors (stage 0, I, II), surgery is usually the treatment of choice. Radiotherapy may be used in patients who are medically unsuitable for surgery. The role of induction chemotherapy in these early stages is still under investigation. Locally or regionally advanced tumors (stage III) are usually too extensive curative surgery, but are still confined to the chest. The standard treatment is chemotherapy plus radiotherapy. Downstaging the tumor with chemotherapy (with or without radiotherapy) may allow surgery in certain cases. Advanced tumors (stage IV) are treated with chemotherapy. Palliative radiotherapy may be used to relieve symptoms. 1. PDQ Treatment Guidelines.

NSCLC stadio 0-IIIA N1 Intervento chirurgico (lobectomia, ecc) resezioni non anatomiche solo in casi particolari RT curativa se CH controindicata dosaggio > 60 Gy Chemioterapia adiuvante ? Radioterapia adiuvante? Chemioterapia neoadiuvante? Stadio 0: Terapia fotodinamica (in paz. selezionati) Surgery is the treatment of choice, lobectomy, pneumonectomy (removal of entire lung), segmentectomy or wedge resection depending on the patient.1 Curative radiotherapy may be used in patients with contra-indications to surgery.1 30-50% of patients resected for stage I/II NSCLC may later develop regional or distant metastases. Adjuvant chemotherapy or radiotherapy following surgery, and neoadjuvant chemotherapy, are currently under investigation.1 1. PDQ Treatment Guidelines.

NCSLC: tipi di intervento chirurgico Pneumonectomia Lobectomia Segmentectomia Wedge-resection

NSCLC stadio I: chirurgia TIPO DI INTERVENTO CHIRURGICO recidiva per tipo di intervento 0.10 50 0.09 Tasso recidiva locoreg. (per persona/ anno) 0.08 40 p=0.008 p<0.05 0.07 0.06 30 locoregionale % recidiva 0.05 0.04 20 0.03 0.02 10 0.01 The recurrence rate after surgery appears to be higher for limited surgery than for lobectomy. The left-hand graph shows the locoregional recurrence rate (per patient per year) in 247 patients with stage IA (T1 N0) NSCLC, who were randomized to either lobectomy or limited (segment or wedge) resection. The recurrence rate was three times higher in the patients undergoing limited resection, and the death rate was increased by 30%.1 Similarly, a retrospective non-randomized study in 173 patients with stage I NSCLC found that the percentage of patients experiencing a local or regional recurrence within 5 years was higher in patients undergoing anatomic segmentectomy than lobectomy.2 1. Ginsberg RJ, Rubinstein LV. Ann Thorac Surg 1995; 60: 615-623. 2. Warren WH, Faber LP. J Thorac Cardiovasc Surg 1994; 107: 1087-1094. 00.0 Resezione limitata (n=122) Lobectomia (n=125) Segmen- tectomia (n=68) Lobectomia (n=105) TIPO DI INTERVENTO CHIRURGICO Warren & Faber 1994 Ginsberg & Rubinstein1995

NSCLC stadio I-II: RT Sopravvivenza in base al dosaggio 80 70 60 Disease-free survival (%) 50 40 30 20 A retrospective review investigated survival in 152 patients with stage I and II NSCLC, who were unable to undergo surgery for medical reasons and received radiotherapy instead.1 The graph shows 2-year disease-free survival by tumor stage (T1, T2 or T3) and radiation dose.1 T1 tumors treated with radiation doses of 65 Gray or more had the best disease-free survival rate, 73% at 2 years.1 This is comparable to the overall 2-year survival rates of approximately 75% (segmentectomy) and approximately 90% (lobectomy) reported separately for resected patients with stage I (T1 or T2, N0) NSCLC.2 1. Dosoretz DE, et al. Int J Radiation Oncology Biol Phys 1992; 24: 3-9. 2. Warren WH, Faber LP. J Thorac Cardiovasc Surg 1994; 107: 1087-1094. 10 Globale >65 Gy <60 Gy DOSAGGIO RT Dosoretz et al 1992

NSCLC: Radioterapia adiuvante Studi randomizzati N. Paz Stadio S 5a (CH / CH+RT) % Rec.Loc. LCSG 1986 230 II - III A 38 / 39 19/ 1 STEPHENS 1996 308 II – III A 19 / 20 14 / 1 MAYER 1997 174 I – III A 20 / 30 24 / 6 PORT 1998 2128 I – IIIA 55 / 48 (2a) N.S. DAUTZENBERG 1999 728 43 / 30 FENG 2000 366 II – IIIA 41 / 43 33 / 13

NSCLC: Chemioterapia adiuvante Studi randomizzati N. Paz Stadio Schema S 5a (CH/CH+CT) SGACLC 309 I – III A P/DOX/UFT 58 / 62 WADA 323 P/VDS/U VS U 49 / 61 / 64 METANALISI 1394 P-based 48 / 53 KELLER 488 II – III A P/VP16 39 (rt) / 38 ALPI 1209 MVP +/- RT 37 / 40 TADA 267 I – IIIA UFT 58 / 74 (8a) TSUBOI 979 I 85 / 89 IALT 1867 P/VP16-VNR 40 / 45

NSCLC stadio III: opzioni terapeutiche Chirurgia (in paz. selezionati in stadio IIIA) Chemioterapia  CH RT postoperatoria (pN2) RT o Chemioradioterapia? Chemioterapia (stadio IIIB con versamento pleurico) Stage IIIA:1 surgery alone in highly selected cases chemotherapy combined with radiotherapy, chemotherapy plus radiotherapy followed by surgery, or chemotherapy after surgery (encouraging results for patients with good performance status) surgery and postoperative radiation therapy (can improve local control, but there is controversy over whether it improves survival) radiation therapy (long-term survival benefit in 5-10% of patients; patients with high performance status are most likely to benefit). Stage IIIB:1 radiation therapy alone (patients with advanced disease and high performance status are most likely to benefit) chemotherapy combined with radiation therapy (modest survival benefits compared with radiation therapy alone) chemotherapy and/or radiation therapy followed by surgery chemotherapy alone (for patients with malignant pleural effusion). 1. PDQ Treatment Guidelines.

NSCLC: Chemioterapia neoadiuvante Studi randomizzati N.Paz Stadio Terapia RO % Resez. SM PASS 14 13 IIIA N2 CH PE+CH - 43 86 85 16 29 ROSELL 30 MIC+CH 60 90 10 20 ROTH 32 28 CEP+CH 35 66 61 11 64 DEPIERRE 119 109 IB-IIIA N1 MIP+CH 78 26 37 * Sopr. a 3 anni

NSCLC stadio III: CT/RT vs RT 0.0 0.5 1.0 1.5 2.0 RT + CT migliore RT (controllo) migliore Buenos Aires Brussels FLCSG 2 Essen SLCSG CEBI 138 WSLCRG/FI Perugia CALGB 8433 EORTC 08842 SWOG 8300a SWOG 8300b Subtotale p=0.005 A meta-analysis used data from 11 randomized clinical trials which compared radiotherapy with radiotherapy plus cisplatin-based chemotherapy in patients with locally advanced NSCLC.1 The graph shows the hazard ratio (relative risk of death) and confidence intervals for each of the 11 trials. The square represents the mean hazard ratio for each trial, and the outer and inner bars show the 95% and 99% confidence intervals. The size of the square represents the size of the trial. The center of the diamond represents the overall hazard ratio from all the trials combined, and its ends represent the 95% confidence interval. The majority of the trials reported a hazard ratio of <1 (to the left of the solid vertical line), indicating superior survival in the groups treated with radiotherapy plus chemotherapy. The overall hazard ratio was 0.87, indicating a 13% lower risk of death for the patients receiving combination treatment (p=0.005). Combined chemotherapy and radiotherapy is an appropriate treatment for patients with good performance status and weight loss of <5%. However, radiotherapy alone may be more appropriate for patients with stage III NSCLC with poor performance status or weight loss of 5% or more during the preceding 3-6 months.2 1. Non-small Cell Lung Cancer Collaborative Group. Br Med J 1995; 311: 899-909. 2. Juretic A, et al. Ann Oncology 1999; 10 (suppl. 6): S93-S98. NSCLC Collaborative Group 1995

NSCLC stadio IIIB-IV: vecchi vs nuovi regimi BSC regimi con CDDP anni 80 Regimi con CDDP anni 90 % risposte obiettive 30 40 Sopravv. Mediana (m) 6 7 - 8 9 - 10 Sopravv 1 anno (%) 10 20

NSCLC stadio IIIB-IV: schemi di chemioterapia studi randomizzati RO (%) 26 38 14 23 27 21.3 21.0 17.3 15.3 SM (mesi) 8.2 8.1 9.2 8.0 7.8 7.4 CRINO’ 1998 BELANI 1998 KELLY 1999 SCHILLER 2000 Schema Mitomicina/ifosfamide/cisplatino Gemcitabina/cisplatino Etoposide/cisplatino Paclitaxel/cisplatino Vinorelbina/cisplatino Paclitaxel/carboplatino Paclitaxel/cisplatino Docetaxel/cisplatino Recent randomized trials have clearly demonstrated the benefit of combining cisplatin with new active agents in NSCLC, resulting in increased tumor response and prolonged median survival compared with treatment with cisplatin alone. However, at present, none of the new agent - platinum combinations has been shown to be clearly superior. Results of two large phase III trials reported at ASCO1,2 show a broad range of response rates (15-27%) with these new combinations, but this does not translate into a significant impact on median survival (range 7.4-8.2 months). 1. Kelly K, et al. Proc ASCO 1999;18:(abs 1777) 1. Schiller JH, et al. Proc ASCO 2000;19:(abs 2)

NSCLC: BSC vs Chemioterapia Metanalisi N. Studi Risultati Conclusioni SOUQUET 7 ↓ Mortalità a 3 e 6 m. CT raccomandata GRILLI 6 Sopravvivenza (6 sett.) CT in paz. selezionati MARINO 8 SM 3.9 vs 6.7 m. NSCLC COLL. GROUP 11 SM 6 vs 8 m.; 16 vs 26% a 1 a. CT migliora sopravvivenza

NSCLC: Chemioterapia di II linea Studi randomizzati N Paz RO % SM m. S 1-a. p SHEPERD BSC TXT10075 100 103 - 6 4.6 7 19 29 0.047 FOSSELLA TXT 100 TXT 75 VNR/IFX 123 127 119 12 8 1 5.6 32 10 0.012 HANNA PMTX 500 285 286 Nr nr 7.9 8.3 30 N.S.

NSCLC: sopravvivenza per terapia Stadio Tipo terapia Sopravv. 5 anni IA - IB CH 40 – 60 IIA – IIB CH + Terapie adiuvanti 20 – 40 IIIA CT neoadiuvante + CH + Terapie adiuvanti 10 – 20 IIIB “buona prognosi” CT + RT IIIB “cattiva prognosi” - IV CT < 5

NSCLC: nuovi farmaci Inibitori Topoisomerasi (CPT11,ecc) Nuovi antifolati (MTA) Nuovi Taxani (BAY 59-8862 ) Inibitori EGFR (MoAb o TKI) Antiangiogenetici (antiVEGF,ecc) Inibitori MMP (Marimastat,ecc) Oligonucleotidi antisenso (ISIS 3521,ecc) Vaccini antitumorali (IGN 101,ecc) Anti COX2 (Celecoxib,ecc) Terapia genica In order to replicate DNA, the two strands must be separated, which causes strain in adjacent areas of the helix. The strain is relieved by DNA topoisomerases, which make a transient break in the DNA backbone to permit unwinding. Topoisomerase inhibitors increase the frequency of these breaks, which eventually triggers programmed cell death.1 DNA synthesis requires a constant supply of nucleotides. The supply of the thymidylate nucleotide can be blocked by inhibition of thymidylate synthase. This enzyme is the target of antifolate drugs such as ZD9331,2 multitargeted antifolate (MTA, LY231514),3 and the benzoquinolone 1843U89.4 1. Fortune JM, et al. Biochemistry 1999; 38: 15580-15586. 2. Plummer R, et al. Eur J Cancer 1999; 35: S4, 285. 3. Rusthoven JJ, et al. J Clin Oncol 1999; 17: 1194-1199. 4. Hanlon MH, Ferone R. Cancer Res 1996; 56: 3301-3306.

NSCLC: Studi clinici con inibitori dell’EGFR Disegno SM (m.) GATZEMEIER GC vs GC+Herceptin 7.2 / 6.3 (TTP) IDEAL 1 IDEAL 2 INTACT 1 INTACT 2 Iressa 250 vs 500 mg CT vs CT + Iressa 250/500 8.2 / 8.0 8.1 / 8.0 11.1 / 9.9 / 9.9 9.9 / 9.8 / 8.7 BONOMI TRIBUTE TALENT Tarceva 150 mg CT vs CT + Tarceva 150 9.0 ND

Carcinoma polmonare a piccole cellule

SCLC: stadiazione Malattia estesa: Tumore non confinato all’emitorace di origine o metastasi a distanza Malattia limitata: Tumore confinato all’ emitorace di origine e/o al mediastino e/o ai linfonodi sovraclaveari Metastatic disease is present at diagnosis in most patients with SCLC. Thus, survival is usually not affected by small changes in the amount of locoregional tumor involvement, as it is for NSCLC. Thus, the detailed TNM staging previously described, although relevant is not commonly employed for staging SCLC. Instead, a simple 2-stage system, limited or extensive stage SCLC, is used. In limited-stage disease the tumor is confined to the hemithorax of origin, the mediastinum and the supraclavicular nodes, which can be encompassed within a ‘tolerable radiation’ therapy port.1 The extensive-stage of SCLC encompasses any tumor too widespread to be included within the definition of limited-stage and any patients with distant metastasis.1 1. Zelen M. Cancer Chemother Rep 1973; 4: 31-42. PDQ Guidelines 2000

SCLC: sopravvivenza % Pazienti Mal. limitata Mal. Estesa Based on US figures from 1992-1997, 5-year survival in patients with SCLC is 6.2%.1 Disease stage is one of the most important prognostic factors in SCLC. In a randomised study, in which two combination chemotherapy regimens were compared, prognostic factors were analysed in 286 patients. Disease stage was the primary pretreatment predictor of 3-year survival; 19.2% of patients with limited-stage disease survived for 3 years, compared with 3.5% with extensive-stage disease.2 The median survival duration for patients treated with combination chemotherapy is 10 to 14 months for patients with limited-stage and 7 to 11 months for those with extensive-stage, the most commonly diagnosed SCLC.3 References 1. Ries LAG, et al (eds). SEER Cancer Statistics Review, 1973-1998, National Cancer Institute, Bethesda, MD, 2001. 2. Kawahara M, et al. Jpn J Clin Oncol 1997; 27: 158-165. 3. Zöchbauer-Müller S, et al. Ann Oncol 1999; 10 (Suppl 6): S83-S91. Mal. limitata Mal. Estesa Ries et al 2001

SCLC: opzioni terapeutiche Malattia limitata chirurgia solo per noduli periferici chemio-radioterapia Malattia estesa chemioterapia + radioterapia in casi selezionati PCI in caso di risposta completa For localized tumors (stage 0, I, II), surgery is usually the treatment of choice. Radiotherapy may be used in patients who are medically unsuitable for surgery. The role of induction chemotherapy in these early stages is still under investigation. Locally or regionally advanced tumors (stage III) are usually too extensive curative surgery, but are still confined to the chest. The standard treatment is chemotherapy plus radiotherapy. Downstaging the tumor with chemotherapy (with or without radiotherapy) may allow surgery in certain cases. Advanced tumors (stage IV) are treated with chemotherapy. Palliative radiotherapy may be used to relieve symptoms. 1. PDQ Treatment Guidelines.

SCLC: chemioterapia di combinazione Cisplatino/Etoposide (PE) Ciclofosfamide/Adriamicina/vincristina (CAV) Ifosfamide/Carboplatino/Etoposide (ICE) Ciclofosfamide/Adriamicina/Etoposide (CAE) Cisplatino/CPT11 Cisplatino/Topotecan Cisplatino/Gemcitabina/Etoposide Carboplatino/Paclitaxel Multiple chemotherapeutic agents possess single-agent activity against SCLC. A number of combination chemotherapy protocols have demonstrated activity in patients with limited-stage SCLC, with overall response rates of 80-95%. These include cisplatin/etoposide (PE), cisplatin/etoposide/vincristine (PEV), cyclophosphamide/doxorubicin/vincristine (CAV), cyclophosphamide/ doxorubicin/etoposide (CAE) and cyclophosphamide/doxorubicin/ vincristine/etoposide (CAVE). In patients with limited stage disease median survivals of 12.4 and 15.1 months have been reported following treatment with CAV and CAVE, respectively. 1,2 In addition, the complete response rate was 16% and 48%, with CAV and CAVE, respectively.1,2 There is some evidence that alternating chemotherapy regimens (PE/CAV) in patients with limited disease may be beneficial.1,3 There is no compelling evidence that maintenance chemotherapy prolongs survival for patients with SCLC. In fact it may produce more toxicity and thus negatively impact on the quality of life.4 1. Fukuoda M, et al. J Natl Cancer Inst 1991; 83: 855-861. 2. Goodman GE, et al. J Clin Oncol 1990; 8: 39-47. 3. Johnston BE, et al. J Clin Oncol 1996; 14: 806-813. 4. Giaccone G, et al. J Clin Oncol 1993; 11: 1230-1240. Zöchbauer-Müller and Huber 1999

SCLC-ML: chemio-radioterapia Metanalisi su 13 studi 100 Chemioterapia + RT (n=1111) 80 Chemioterapia (n=992) Sopravv. % p=0.001 60 40 20 A meta-analysis of the 13 largest trials showed that combined chemotherapy and chest RT was more effective than chemotherapy alone. In this study, administration of thoracic RT led to a 14% reduction in mortality rate (p=0.001), which corresponded to a 5% increase in the 3-year survival rate.1 A similar result was also demonstrated in another meta-analysis of 11 randomized trials.2 Most of the benefit occurred in patients <55 years. Thus, in limited stage SCLC, combination chemotherapy plus chest RT is considered a standard treatment for patients with limited-disease SCLC.3 1. Pignon JP, et al. N Engl J Med 1992; 327: 1618-1624. 2. Warde P, Payne D. J Clin Oncol 1992; 10: 890-895. 3. PDQ Guidelines, 2000. 1 2 3 4 5 Anni Pignon et al 1992

SCLC: Trattamento della malattia limitata CH  poliCT/RT combinate 1/3 esterno Nodulo solitario T2 poliCT + RT concomitante 2/3 interni SCLC-ML poliCT + RT concomitante Buon PS Even for a small solitary nodule that has been completely resected subsequent chemotherapy is indicated.1 The majority of patients diagnosed with positive mediastinal nodes undergo combination chemotherapy with concurrent chest radiotherapy (RT).1,2 Patients presenting with superior vena cava syndrome or patients with poor performance status and extensive cormordid disease can be treated with combination chemotherapy without RT.1 Prophylactic cranial irradiation (PCI) can be considered in patients who are in complete remission following treatment with chemotherapy with or without chest irradiation.1,2 1. NCCN Guidelines, 2000. 2. PDQ Guidelines, 2000. Tutte le restanti presentazioni Cattivo PS poliCT RT NCCN guidelines 2000

LD-SCLC: RT profilattica cerebrale No PCI (n=149) PCI (n=145) p<10-13 80 60 % Recidive cerebrali 40 20 Despite the high response rates to chemotherapy, after 2 years the risk of brain metastasis is 50-80%, resulting in extremely low survival rates. This study showed that patients who are in complete remission have a 60% risk of developing CNS metastases within 2 to 3 years of treatment, and administration of PCI reduces the risk by more than 50%.1 Several randomized studies have failed to demonstrate a benefit for PCI in improving overall survival, and side effects, such as neuropsychiatric abnormalities have been a concern. However, neurological abnormalities have been shown to exist in 30-40% of SCLC patients prior to PCI and a recent meta-analysis demonstrated an absolute 5.4% increase in 3-year survival rate in favor of PCI.2 It is now generally accepted that PCI should be administered to patients with limited-stage disease in complete remission after induction chemotherapy.2 1. Arriagada R, et al. J Natl Cancer Inst 1995; 87: 183-190. 2. Zöchbauer-Müller S, et al. Ann Oncol 1999; 10 Suppl 6: 83-91. 12 24 36 48 60 Mesi Arriagada et al 1995

Terapia del SCLC-ME ES-SCLC M.estesa Sintomatico/grave Osso poliCT (+ ev. PCI) M.estesa RT Sintomatico/grave ES-SCLC Osso Asintomatico poliCT Sintomatico RT+ poliCT M. Estesa + Problemi specifici SNC Since disseminated disease is present in patients with extensive-stage SCLC, combination chemotherapy is the most important treatment modality.1,2 Combination chemotherapy plus chest RT does not improve survival in patients with extensive disease, compared with chemotherapy alone.1 However, radiation therapy plays an important role in palliation of symptoms of the primary tumor and of metastatic disease, particularly in the brain, spinal cord and bone.1,2 For severely debilitated patients with extensive disease, a low intensity chemotherapy regimen may provide palliation with low associated toxicity. 1. PDQ guidelines, 2000. 2. NCCN guidelines, 2000. Asintomatico PoliCT (± RT) Midollo spinale RT + steroidi poi poliCT NCCN guidelines 2000

SCLC: risposta alla terapia MALATTIA LIMITATA Risposte obiettive: 85% (~30% complete) Sopravvivenza mediana non trattati: 3 mesi trattati: 18 mesi Sopravvivenza a 5 anni 10-20% MALATTIA ESTESA Risposte obiettive: 70% (~15% complete) non trattati: 6 settimane trattati: 9 mesi Sopravvivenza a 5 anni < 5% The combination chemotherapy regimens commonly used in extensive-stage SCLC appear to have similar relative effectiveness; with overall response rates of 70-85%, complete response rates of 10-40% and median survivals of 7-11 months.1 Long-term survivors are rare. 1. PDQ Guidelines, 2000. PDQ guidelines 2000

SCLC recidivo: opzioni terapeutiche Terapia sintomatica Chemioterapia di II linea o inserimento In studio clinico Refrattario (durante CT) SCLC recidivato Recidiva precoce (entro 3 mesi) Palliative therapy is very important in patients with recurrent SCLC. Palliation of symptoms with short-term local control and external-beam radiation therapy can be carried out.1 In addition, in patients with intrinsic endobronchial obstructing lesions or extrinsic compression, endobronchial laser therapy and/or brachytherapy may be beneficial.1 Endobronchial stents can be inserted in patients with malignant airway obstruction.1 Late relapsing patients with a long-treatment-free interval frequently respond to combination chemotherapy, which may be identical to their first-line treatment (response rates of up to 50-60%).1 Both refractory and early relapsing patients with a short treatment-free interval, only have a small chance of responding to any drug.1,2 These patients are candidates for Phase II studies with new agents.1,2 1. PDQ Guidelines, 2000. 2. Huisman C, et al. Cancer Treatment Rev 1999; 25: 1999-2206. Ripresa terapia di I linea Tardiva NB. 95% recidivano Sopravv. Media dalla recidiva 4-6 mesi NCCN Guidelines 2000

SCLC: nuovi farmaci Classe Farmaco Taxani docetaxel; paclitaxel Inibitori topoisomerasi Analoghi del platino Retinoidi Agenti alchiilanti Antimetaboliti Inibitori MMP Vaccini antitumorali Oligonucleotidi antisenso Inibitori c-kit Farmaco docetaxel; paclitaxel irinotecan; topotecan ZD0473 tretinoina nitrullina Gemcitabina Marimastat,Prinomastat Anti BEC-2 ISIS 5132 STI 571 There is clearly a need for new drug regimens to improve survival in patients with SCLC and there are several new drugs showing encouraging results in clinical trials for SCLC. As single agents in extensive- stage SCLC patients, the taxoid, docetaxel gives comparable survival outcomes to that of standard single agent treatment.1,2 Docetaxel is currently in Phase II combination trials. The response rates of paclitaxel and irinotecan as single agents in Phase II trials were also similar to those of established drugs, and they are also currently being examined in combination chemotherapy trials.3,4 ZD0473 is a platinum drug designed with the capacity to overcome acquired or de novo resistance, particularly to overcome thiol-mediated resistance. Phase II trials of this drug are ongoing in a number of tumour types including SCLC and NSCLC5 The 9-cis retinoid, tretinoin has demonstrated cytotoxicity against SCLC cells in vitro.6 It is currently in Phase II trials in the USA. Nitrullyn, an alkylating agent is currently in Phase II trials in patients with SCLC in Russia. 1. Hesketh PJ, et al. Cancer J Sci Am 1999; 5: 237-241. 2. Postmus PE, et al. Sem Oncol 1998; 25: 79-82. 3. Ettinger DS. Sem Rad Oncol 1999; 9: 148-150. 4. Zöchbauer-Müller S, et al. Ann Oncol 1999; 19: S83-S91. 5. Trigo JM, et al. Proc Am Soc Clin Oncol 1999; 18: 169. 6. Rosati R, et al. Anticancer Res 1998; 18: 4071-405.

Altri provvedimenti terapeutici Metastasi isolata a SNC o surrene intervento chirurgico (+ RT se SNC) Sindrome VCS posizionamento stent cavale steroidi, RT e/o CT, ecc Ostruzione bronchiale laserterapia disostruttiva posizionamento di stent bronchiale Localizzazione rachidea Decompressione chirurgica entro 48 ore RT, steroidi, ecc Versamento pleurico neoplastico posizionamento di drenaggio toracico chemioterapia intracavitaria e/o talcaggio pleura Terapie di supporto