Pubblicazioni

Autori:

Orsi, G; Di Marco, M; Cavaliere, A; Niger, M; Bozzarelli, S; Giordano, G; Noventa, S; Rapposelli, I G; Garajova, I; Tortora, G; Rodriquenz, M G; Bittoni, A; Penzo, E; De Lorenzo, S; Peretti, U; Paratore, C; Bernardini, I; Mosconi, S; Spallanzani, A; Macchini, M; Tamburini, E; Bencardino, K; Giommoni, E; Scartozzi, M; Forti, L; Valente, M M; Militello, A M; Cascinu, S; Milella, M; Reni, M

Titolo:

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey

Anno:

2021

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Referee:

No

Nome rivista:

ESMO OPEN

ISSN Rivista:

2059-7029

N° Volume:

6

Numero o Fascicolo:

5

Intervallo pagine:

1-10

Parole chiave:

chemotherapy activity; chemotherapy dose intensity; chemotherapy toxicity; germline BRCA; pancreatic cancer; Antineoplastic Combined Chemotherapy Protocols; BRCA1 Protein; Cisplatin; Germ Cells; Humans; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms

Breve descrizione dei contenuti:

Background: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting.Patients and methods: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed.Results: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021 were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three-(81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS.Conclusions: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.

Id prodotto:

126261

Handle IRIS:

11562/1063748

ultima modifica:

28 marzo 2023

Citazione bibliografica:

Orsi, G; Di Marco, M; Cavaliere, A; Niger, M; Bozzarelli, S; Giordano, G; Noventa, S; Rapposelli, I G; Garajova, I; Tortora, G; Rodriquenz, M G; Bittoni, A; Penzo, E; De Lorenzo, S; Peretti, U; Paratore, C; Bernardini, I; Mosconi, S; Spallanzani, A; Macchini, M; Tamburini, E; Bencardino, K; Giommoni, E; Scartozzi, M; Forti, L; Valente, M M; Militello, A M; Cascinu, S; Milella, M; Reni, M, Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey «ESMO OPEN» , vol. 6 , n. 5 , 2021 , pp. 1-10

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo