Table 2.
Major studies regarding palliative therapy in elderly patients with advanced/metastatic colorectal cancer
| Ref. | Type of study | No. of total patients | No. of older patients/age (yr) | Endpoint | Outcome |
| Folprecht et al[43] | Retrospective analysis of data from 22 European trials | 3825 | 629 (16%)/≥ 70 | 5-FU-based CTx in older vs younger patients | |
| (1) ORR | (1) ORR: 23.9% vs 21.1%; P = 0.14 | ||||
| (2) PFS | (2) PFS: 5.5 mo vs 5.3 mo; P = 0.01 | ||||
| (3) OS | (3) OS: 10.8 mo vs 11.3 mo; P = 0.31 | ||||
| Folprecht et al[49] | Pooled analysis of data from four randomized phase III trials | 2691 | 559 (22%)/≥ 70 | Irinotecan/5-FU vs 5FU as first-line CTx in younger and older patients: | Improved with irinotecan-based CTx: |
| (1) ORR: | |||||
| (1) ORR | younger, 46.6% vs 29.0%; P < 0.01 | ||||
| (2) PFS | elderly, 50.5% vs 30.3%; P < 0.01 | ||||
| (3) OS | (2) PFS: | ||||
| younger, HR = 0.77 (95%CI: 0.70-0.85; P < 0.01) | |||||
| elderly, HR = 0.75 (95%CI: 0.61-0.90; P < 0.01) | |||||
| (3) OS: | |||||
| younger, HR = 0.83 (95%CI: 0.75-0.92; P < 0.01) | |||||
| elderly, HR = 0.87 (95%CI: 0.72-1.05; P = 0.15) | |||||
| Jackson et al[50] (BICC-C trial) | Randomized phase III in a 3-by-2 design | 430 | 117 (21%)/> 70 | Irinotecan + fluoropyrimidine at period 1 and irinotecan + 5-FU/LV + bevacizumab at period 2 in the older vs younger | Period 1: |
| (1) PFS: 7.5 mo vs 6.6 mo, HR = 0.98 (95%CI: 0.74-1.29) | |||||
| (2) OS: 21.2 mo vs 19.0 mo | |||||
| (1) PFS | Period 2: | ||||
| (2) OS | (1) PFS: 10.6 mo vs 7.6 mo; P = 0.14 | ||||
| (2) OS: 19.4 mo vs 25.1 mo | |||||
| Seymour et al[51] (MRC FOCUS2) | Open-label, multi-center, randomized phase III | 438 | 199 (43%)/≥ 75 | a. IV infusion 5-FU/LV | (1) PFS (addition of oxaliplatin vs no addition): 5.8 mo vs 4.5 mo, HR = 0.84 (95%CI: 0.69-1.01; P = 0.07) |
| b. Oxaliplatin + 5-FU | (2) Capecitabine did not improve QoL | ||||
| c. Oxaliplatin + capecitabine | |||||
| d. Capecitabine | |||||
| (1) PFS (a vs b and c vs d) | |||||
| (2) QoL with capecitabine instead of 5-FU | |||||
| Figer et al[52] (OPTIMOX1 study) | Exploratory cohort | 620 | 37 (6%)/76-80 | FOLFOX4 until PD or FOLFOX7 for 6 cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (1) PFS and (2) OS in the older vs younger | (1) PFS: 9.0 mo vs 9.0 mo; P = 0.63 |
| (2) OS: 20.7 mo vs 20.2 mo; P = 0.57 | |||||
| (3) AEs ≥ grade 3: neutropenia, 41% vs 24%; P = 0.03, neurotoxicity, 22% vs 11%; P = 0.06 | |||||
| Cassidy et al[53] | Retrospective pooled analysis (AVF2107g, AVF219g, NO16966, E3200 trials) | 3007 | 1142 (38%)/≥ 65 | 5-FU/LV-based CTx ± bevacizumab | (1) ≥ 65 yr: 9.3 mo (+ bevacizumab) vs 6.9 mo, HR = 0.58 (95%CI: 0.49-0.68; P < 0.01) |
| (1) PFS | ≥ 70 yr: 9.2 mo (+ bevacizumab) vs 6.4 mo, HR = 0.54 (95%CI: 0.44-0.66; P < 0.01) | ||||
| (2) OS | (2) ≥ 65 yr: 17.9 mo (+ bevacizumab) vs 15 mo, HR = 0.85 (95%CI: 0.74-0.97; P = 0.02) | ||||
| ≥ 70 yr: 17.4 mo (+ bevacizumab) vs 14.1 mo, HR = 0.7 (95%CI: 0.66-0.93; P < 0.01) | |||||
| Cunningham et al[55] (AVEX trial) | Open-label, multi-center, randomized phase III | 280 | 280 (100%)/≥ 70 | (1) PFS | (1) PFS: 9.1 mo (+ bevacizumab) vs 5.1 mo, HR = 0.53 (95%CI: 0.41-0.61; P < 0.01) |
| a. Capecitabine (n = 140) | (2) AEs ≥ grade 3: 40% (+ bevacizumab) vs 22% | ||||
| b. Capecitabine + bevacizumab (n = 140) | |||||
| (2) Assessment of treatment-related AEs | |||||
| Sastre et al[59] (Spanish TTD Group Study) | Phase II | 66 | 66 (100%)/≥ 70 | Cetuximab + capecitabine as first-line therapy | (1) ORR: 31.8% (48.3% in w-KRAS vs 20.7% in m-KRAS; P = 0.027) |
| (1) ORR | (2) PFS: 7.1 mo, OS: 16.1 mo | ||||
| (2) PFS, OS | (3) AEs ≥ grade 3: paronychia (29.6%), rash (29.6%) | ||||
| (3) Safety |
AEs: Adverse events; CTx: Chemotherapy; 5-FU: 5-Fluorouracil; IV: Intravenous; m-KRAS: Mutant-type KRAS; ORR: Overall response rate; OS: Overall survival; PD: Progression of disease; PFS: Progression-free survival; QoL: Quality of life; w-KRAS: Wild-type KRAS.