Background: Colorectal cancer (CRC) incidence arise in older patients. Aging is associated with decreased functional reserve of multiple organ systems with worsening of behaviour of pharmacokinetics and pharmacodynamics of drugs. Elderly patients (EP) show enhanced susceptibility to cytotoxic therapy, especially for bone-marrow, mucosal, CNS and neuroperipheral (NPH) toxicity (TOX). Treatment of EP with CRC must take in account the prevention of these effects. Combination Capecitabine (XEL) + Oxaliplatin (OX) seems to be safe and feasible for this purpose especially if dose drugs adjustment will be performed. Aims: To evaluate a flat dose schedule of XEL (1000 mg b.i.d.)+OX (130 mg/sqm) q3wks vs XEL (1000 mg/sqm b.i.d.)+OX (130 mg/sqm) q3wks. Methods: a totally of 42 elderly PTS Dukes C stage CRC (m/age 70) were treated after written informed consent acquired. 21 pts (Group A) were treated as follows: XEL (1000 mg/sqm/os b.i.d.)+OX (130 mg/sqm/2 h/i.v.i.)(Schedule A). Another group of 21 pts (Group B) received XEL 1000 mg/b.i.d (flat dose)+OX (130 mg/sqm/2h/i.v.i.)(Schedule B). We evaluated GFR of each patient and CHT was adjusted according with Kintzel&Dorr formula. All patients were evaluated for common treatment-related adverse events as haematological, liver, mucosal, CNS&NPH TOX, N&V and HFS, according to the ECOG. All patients were also evaluated for ADL/IADL both with ECOG PS and number of comorbidities. Plasma VEGF’s values were also evaluated by an enzyme-linked immunosorbent assay (ELISA), at baseline (B) and at the end of treatment (E). The benefit obtained by treated patients was evaluated using the Wilcoxon signed rank test (baseline versus post-treatment values). Results: Both Group A & B were evaluated at the end of treatment. Group A PTS received about 80% of expected dose only; Group B received full expected dose; TOXs: Group A: haematological: 18 PTS = G1; 3 PTS = G2. Liver: 8 PTS = G1; 5 PTS = G2; 1 PTS = G3. HFS: 5 PTS = G2; 2 PTS = G3/4; CNS&NPH: 15 PTS = G1/2. Group B: haematological: 6 PTS = G1; Liver: 10 PTS = G1; CNS&NPH: 4 PTS = G1. VEGF’s values (pg/ml): Group A: B = mv 522 (380 - 728); E = mv 402 (189 - 537); p=0,001. Group B: B = mv 527 (331 - 753); E = mv 335 (208 - 697); p=0,0029. Conclusions: The study show that schedule B have more safe and feasible profile compared with schedule A. Further, XEL flat dose (according with Lokich, Canc. Invest., 2004) improves PTS compliance for oral delivery (no needs to different tablets for size and concentration to reach the expected dose). No delivery delay was necessary in schedule B PTS. Only slight general TOX was also noted in schedule B PTS vs schedule A. Author believe that XEL flat dose administration works as antiangiogenic control in CRC elderly PTS, with preservation of DI, even if a larger number of PTS will be necessary to permit statistical analysis. DFS and OS are still under evaluation.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]