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Research Papers:

Multidisciplinary palliation for unresectable recurrent rectal cancer: hypoxic pelvic perfusion with mitomycin C and oxaliplatin in patients progressing after systemic chemotherapy and radiotherapy, a retrospective cohort study

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Oncotarget. 2019; 10:3840-3851. https://doi.org/10.18632/oncotarget.26972

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Stefano Guadagni, Giammaria Fiorentini, Andrea Mambrini, Francesco Masedu, Marco Valenti, Andrew Reay Mackay, Donatella Sarti, Enrico Ricevuto, Marco Clementi, Marco Catarci, Gianni Lazzarin and Gemma Bruera

Abstract

Stefano Guadagni1, Giammaria Fiorentini2, Andrea Mambrini3, Francesco Masedu1, Marco Valenti1, Andrew Reay Mackay1, Donatella Sarti2, Enrico Ricevuto1,4, Marco Clementi1, Marco Catarci5, Gianni Lazzarin1 and Gemma Bruera1,4

1 Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, L’Aquila, Italy

2 Department of Oncology and Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro, Italy

3 Oncology Unit, Azienda USL Toscana Nord Ovest, Massa Carrara, Italy

4 Oncology Territorial Care S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L’Aquila, Italy

5 General Surgery Unit, “C. e G. Mazzoni” Hospital, Ascoli Piceno, Italy

Correspondence to:

Stefano Guadagni,email: stefano.guadagni@univaq.it

Keywords: hypoxic pelvic perfusion with mitomycin C and oxaliplatin; unresectable recurrent rectal cancer; retrospective cohort study

Received: April 04, 2019     Accepted: May 05, 2019     Published: June 11, 2019

ABSTRACT

Background

Innovative systemic treatments and loco-regional chemotherapy by hypoxic pelvic perfusion (HPP) have been proposed for unresectable recurrent rectal cancer (URRC). Regorafenib and trifluridine-tipiracil reported significantly increased PFS 1.9-2.0 months, OS 6.4-7.1 months vs placebo, respectively. Present study evaluated safety and efficacy of mitomycin/oxaliplatin HPP associated to intravenous cetuximab, and of third line systemic therapy in clinical practice.

Methods

HPP consisted of: isolation, perfusion, chemofiltration. Patients received mitomycin 25 mg/m2 and oxaliplatin 80 mg/m2 during HPP; from days 21 to 28, cetuximab 250 mg/m2/week. In case of partial response or stable disease, HPPs were repeated every 8 weeks. In control group, systemic third and further lines of therapy were defined in clinical practice according to clinical (age, comorbidities, performance status), biological parameters (KRAS, NRAS, BRAF genotype).

Results

From 2005 to 2018, 49 URRC patients were enrolled; 33 in HPP/target-therapy, 16 in systemic therapy control group. No HPP related complications were reported. Most common adverse events were skin, bone marrow toxicities. In HPP/target-therapy group, ORR and DCR were 36.4 and 100%; in systemic therapy control group, 18.7 and 31.25%, respectively. In HPP/target-therapy compared with systemic therapy group, respectively, DCR seemed significantly favourable (P = 0.001), as PFS 8 vs 4 months (P = 0.018), and OS 15 vs 8 months (P = 0.044).

Conclusions

Present data showed that integration of HPP/target-therapy may be effective in local control, and efficacy as third line treatment of URCC patients. This therapeutic strategy deserves further prospective randomized trials to be compared to conventional systemic treatments.



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