Recently, Cp and Temozolamide (Tz) treatment has been investigated in NET in several studies, with heterogeneous populations and outcomes. Cp plus Tz reported a median PFS of about 13 months and it seems more efficient in pancreatic NET. Results from phase II and non-randomized trials with fluoropyrimidine in combination with SSA in well-differentiated (WD) NET are limited, and considered investigational. We review our experience in metastatic WDNET patients (pt) treated with only Cp and SSA, in order to identify eventual subgroups that may benefit from this treatment in terms of efficacy and tolerability.
From October 2005, 40 WDNET pt with progressive disease after failure of SSA and/or Everolimus, PRRT, other Chemotherapy, were treated with Cp and SSA. The primary tumors site was pancreas (P) in 17 pt, intestine (I) in 13 pt, lung (L) in 6 pt, and unknown (U) in 4 pt. Pt received Cp 1000 mg/mq/bidie days 1-14 and SSA (octreotide LAR 30mg 1 fl im q28 or lanreotide LAR 120mg 1 fl im q28). Treatment efficacy was evaluated by response rate according to RECIST criteria and in terms of Progression Free Survival (PFS). Safety and tolerability were evaluated following CTCAE v4 criteria.
Seven pt (17,5%%) had a Partial Response, 17 pt (42,5%) showed Stable Disease, 16 (40%) pt showed Progrssive Disease; median PFS was 6,1 (1-72,2+) months, 3 pt are still on treatment. In I-NET median PFS was 25,3 (2,2-70,8+)months: in particular G1 I-NET and G2 I-NET mPFS was 46,2 (13,5-70,8+) months and 4,3 (2,2-5,5+) months respectively. In P-NET median PFS was 7,3 (2,0-72,2+)months: in particular G1 P-NET and G2 P-NET mPFS was 7,5 (2,0-72,2+) months and 6,1 (2,5-34,0) months respectively. In L NET median PFS was 5,4 (1,4-6,6) months, in U NET it was 2,3 (1,0-11,6) months. At a median follow-up of 40 months, median OS was 48,7 (2,43-85,7+) months. Reported G1-G2 toxicities were diarrhea, nausea, asthenia; G3-G4 toxicities were not reported.
Cp plus SSA showed interesting activity and efficacy in pretreated pt with progressive WDNET with acceptable toxicity. In particular, G1 I-NET pt showed particular prolonged mPFS and in this group Cp plus SSA seems a valid therapeutic option.
Clinical trial identification
Legal entity responsible for the study
Azienda Ospadaliera Universitaria Pisana
Medical Oncology Department Pisa
All authors have declared no conflicts of interest.