APPROPRIATEZZA ED INAPPROPRIATEZZA DELLE PRESCRIZIONI DI ANTIEMETICI Fausto Roila S.C. Oncologia Medica, Terni

TIPI DI NAUSEA E VOMITO ASSOCIATI CON LA CHEMIOTERAPIA NAUSEA E VOMITO ACUTO NAUSEA E VOMITO RITARDATO NAUSEA E VOMITO ANTICIPATORIO

POTENZIALE EMETOGENO DELLA CHEMIOTERAPIA ALTO Rischio in quasi tutti i pazienti (>90%) MODERATO Rischio nel 30% - 90% dei pazienti BASSO Rischio nel 10% - 30% dei pazienti MINIMO Rischio in meno del 10% dei pazienti

POTENTIALE EMETOGENO DEI FARMACI CHEMIOTERAPICI PER VIA EV GRADO FARMACO ALTO Cisplatino Mecloretamina Streptozocina Ciclofosfamide > 1500 mg/m 2 Carmustina Dacarbazina Regimi AC o EC (pts ca. mammella)

GRADO FARMACO MODERATO Oxaliplatino Carboplatino Citarabina> 1 gr/m 2 Ifosfamide Ciclofosfamide < 1500 mg/m 2 Adriamicina Daunorubicina Epirubicina Idarubicina Irinotecan Bendamustina Azacitidina POTENZIALE EMETOGENO DEI FARMACI CHEMIOTERAPICI PER VIA EV

POTENZIALE EMETOGENO DEI FARMACI CHEMIOTERAPICI PER VIA EV POTENZIALE EMETOGENO DEI FARMACI CHEMIOTERAPICI PER VIA EV GRADO FARMACO BASSO Docetaxel Paclitaxel Mitoxantrone Topotecan Etoposide Pemetrexed Metotrexate Mitomcina Gemcitabina Cytarabina  100 mg/m 2 5-Fluorouracile Bortezomib Ixabepilone

POTENZIALE EMETOGENO DEI FARMACI CHEMIOTERAPICI PER VIA EV GRADO FARMACO MINIMO Bleomicina Busulfano 2-Clorodeossiadenosina Fludarabina Vinblastina Vincristina Vinorelbina

POTENZIALE EMETOGENO DEI FARMACI CHEMIOTERAPICI PER VIA ORALE GRADO FARMACO ALTO MODERATO Exametilmelamina Procarbazina Ciclofosfamide Temozolomide Vinorelbina Imatinib

POTENZIALE EMETOGENO DEI FARMACI CHEMIOTERAPICI PER VIA ORALE GRADO FARMACO BASSO MINIMO Capecitabina Etoposide Tegafur uracile Everolimus Lapatinib, Sunitinib Lenalidomide, Talidomide Clorambucil Idrossiurea L-Fenilalanina mostarda 6-Tioguanina Metotrexate

GUIDELINE UPDATE FOR MASCC AND ESMO IN THE PREVENTION OF CHEMOTHERAPY- AND RADIOTHERAPY- INDUCED NAUSEA AND VOMITING: RESULTS OF THE PERUGIA CONSENSUS CONFERENCE Roila F, et al. Ann Oncol 2010; 21 (Suppl.5):

PROFILASSI: RACCOMANDAZIONI 2010 ACUTA RITARDATA Cisplatino 5HT3+DEX+Apr DEX+Apr AC 5HT3+DEX+Apr Apr Non-AC MEC Palo+DEX DEX Low EC DEX or 5HT3 or DA no Minimal EC no no MEC= moderate emetogenic chemotherapy

THE EFFECT OF GUIDELINE-CONSISTENT ANTIEMETIC THERAPY ON CHEMOTHERAPY- INDUCED NAUSEA AND VOMITING (CINV): THE PAN EUROPEAN EMESIS REGISTRY (PEER) Aapro M, et al. Ann Oncol 2012; 23:

Objectives Primary Objective –To compare the proportion of patients with Complete Response (CR = No emesis and no use of rescue therapy) during the first 120 hours post-chemotherapy among patients who receive guideline consistent chemotherapy prophylaxis (GCCP) for highly and moderately emetogenic chemotherapies (HEC or MEC) with those who receive guideline inconsistent chemotherapy prophylaxis (GICP) during Cycle 1. –Secondary Objectives –To describe the use of CINV prophylaxis and rescue medication therapies among HEC and MEC patients. –To describe the nausea experience among HEC and MEC patients who receive guideline consistent and inconsistent CINV prophylaxis.

METHODS (1) Study Design - This was a multi-country, multi-site, prospective, observational study of adult patients who were 18 years and older and who initiated HEC or MEC for cancer treatment. -Patients were recruited from 8 European countries (France, Italy, Spain, UK, Sweden, Belgium, Austria and The Netherlands) and were followed for at least one cycle of chemotherapy and up to three cycles -Daily diaries were completed by patients for 6 days from single day chemotherapy administration. The dairies included time and date of emesis episodes, severity of nausea (0-100 VAS) every 24 hours, and use of rescue medication.

RESULTS A total of 1148 patients were enrolled between September 2009 and June 2010 at 52 study centers. 991 patients comprised the evaluable patient population for analysis, after excluding patients not meeting inclusion/exclusion criteria and not returning a completed cycle one diary. All analyses reported here are from cycle 1 chemotherapy.

RESULTS (%) GCAP GIAP p No. of patients Complete response No vomiting n.s. No nausea No nausea or vomiting

PREVALENCE OF GCAP (%) HEC Female AC MEC No. of patients Acute phase Delayed phase Overall phase

PRESCRIPTION OF GIAP (%) No. % HEC day DEXAMETHASONE NK1-RA HT3 RA

PRESCRIPTION OF GIAP (%) No. % HEC day DEXAMETHASONE NK1-RA HEC day 3 DEXAMETHASONE NK1-RA HEC day 4 DEXAMETHASONE

PRESCRIPTION OF GIAP (%) No. % FEMALE AC day DEXAMETHASONE NK1-RA HT3 RA

PRESCRIPTION OF GIAP (%) No. % FEMALE AC day DEXAMETHASONE and/or NK1-RA FEMALE AC day 3 DEXAMETHASONE and/or NK1-RA

PRESCRIPTION OF GIAP (%) No. % MEC day DEXAMETHASONE HT3 RA

PRESCRIPTION OF GIAP (%) No. % MEC day DEXAMETHASONE or 5-HT3 RA MEC day 3 DEXAMETHASONE or 5-HT3 RA

CONCLUSIONS Guideline consistent chemotherapy prophylaxis significantly increases the proportion with complete response following HEC and MEC, in the overall, acute, and delayed phases The prevalence of guideline consistent chemotherapy prophylaxis was lowest for the higher risk regimens (MEC > Female AC > HEC) Efforts to improve guideline consistent prophylaxis, particularly among patients receiving HEC and females receiving AC, are needed.

CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING IN ITALIAN CANCER CENTERS: RESULTS OF CINVDAY, A PROSPECTIVE, MULTICENTER STUDY De Tursi M, et al. Tumori 2014; 100: e309-e313

LO STUDIO N° pts: 502 Sesso: femmine 58.7% Setting: adiuvante 22.7% maschi 41.4% metastatico 73.3% Tumore primitivo: Chemioterapia -colonretto 29.1% - cisplatino 15.7% - mammella 25.1% - antracicline 8.1% - polmone 11.7% - taxani 17.7% - ovaio 6.1% - FOLFIRI - FOLFOX 24.5% - pancreas 5.8% - monochemio 29.6% - biologica 4.4%

APPROPRIATEZZA DELLE PRESCRIZIONI Rischio: alto moderato basso minimo Appropriate = verde Non appropriate: rosso

RISULTATI Globalmente l’aderenza alle linee guida era del 19.3% Nel HEC e MEC il 10% dei pts non riceve un 5-HT3 antagonista. Un NK1 antagonista era usato solo nel 8% dei pts e solo nel 2% dei pts sottoposti a HEC.

CONCLUSIONI - Molti pts sottoposti a chemioterapia HEC e MEC non ricevono i trattamenti antiemetici raccomandati, in particolare gli NK1 antagonisti - Molti pazienti sottoposti a chemioterapia LEC e di minimo potere emetogeno sono overtreated. Sarebbe interessante vedere quanti di questi pazienti ricevono antiemetici di ultima generazione (palonosetron e NK1 antagonisti)

IGAR, Ann Oncol 1998; 9: TRANSFERABILITY TO CLINICAL PRACTICE OF THE RESULTS OF CONTROLLED CLINICAL TRIALS: THE CASE OF ANTIEMETIC PROPHYLACTIC TREATMENT FOR CANCER CHEMOTHERAPY- INDUCED NAUSEA AND VOMITING

DRUG UTILIZATION REVIEW ON ANTIEMETICS ptsChemotherapy Cisplatin140 High-moderate emetogenic742 Low emetogenic oncological centersResearch on Antiemetics* hospital22no657 (53.1%) university11yes581 (46.9%) *At least a participation in an antiemetic study published in an international journal in the last 10 years

ANTIEMETICS PRESCRIBED ACCORDING TO THE CHEMOTHERAPY EMETOGENIC POTENTIAL 338 (100) 36 (10.6) 125 (37.0) 30 (8.9) 41 (12.1) 50 (14.8) 10 (3.0) 0 9 (2.7) 37 (10.9) 742 (100) 314( 42.3) 341 (46.0) 21 (2.8) 5 (0.7) 27 (3.6) 9 (1.2) 5 (0.7) 11 (1.5) 140 (100) 107 (76.4) 32 (22.9) 0 1 (0.7) 0 No. Of patients (%) -5-HT 3 antagonist + steroids ± other -5-HT 3 antagonist ± other Steroids Metoclopramide Alizapride Steroids + metoclopramide Steroids + alizapride Other No antiemetic prophylaxisLOW No. (%) HIGH- MODERATE No. (%) HIGH EMETOGENIC POTENTIAL

CONCLUSIONI Il trattamento antiemetico presenta importanti aree di inappropriatezza: - la non prescrizione del NK1 antagonista nelle terapie di alto potenziale emetogeno (CDDP, AC, EC) - la prescrizione dei 5-HT3 antagonisti nelle terapie a basso potenziale emetogeno (Taxani, pemetrexed, gemcitabina, etc).