First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study
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Gianluca Tomasello1, Nicola Valeri2,3, Michele Ghidini1, Elizabeth C. Smyth3, Wanda Liguigli1, Laura Toppo1, Rodolfo Mattioli4, Alessandra Curti1, Jens C. Hahne2, Federica M. Negri1, Stefano Panni1, Margherita Ratti1, Silvia Lazzarelli1, Fabiana Gerevini1, Chiara Colombi1, Andrea Panni5, Massimo Rovatti6, Leonardo Treccani7, Mario Martinotti6 and Rodolfo Passalacqua1
1Oncology Division, ASST Ospedale di Cremona, Cremona, Italy
2Division of Molecular Pathology, The Institute for Cancer Research, Sutton, London, UK
3Department of Medicine, The Royal Marsden Hospital, Sutton, London, UK
4Oncology Division, Ospedali Riuniti Marche Nord, Fano, Italy
5Pathology Division, ASST Ospedale di Cremona, Cremona, Italy
6Surgery Division, ASST Ospedale di Cremona, Cremona, Italy
7Radiology Division, ASST Ospedale di Cremona, Cremona, Italy
Gianluca Tomasello, email: email@example.com
Keywords: gastric cancer; DCF; panitumumab; dose-dense; chemotherapy
Received: July 20, 2017 Accepted: November 15, 2017 Published: December 04, 2017
Background: Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy.
Methods: HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression.
Results: From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment.
Conclusions: Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required.
Clinical trial information: 2009-016962-10.
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