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Objectives To assess the toxicity patterns and effectiveness of doublet chemotherapy when administered at reduced doses of 20% (FOLFOX or FOLFIRI) in combination with anti-EGFR antibodies (cetuximab or panitumumab) in old, vulnerable patients with metastatic colorectal cancer (mCRC). Patients and methods We performed a retrospective observational study of RAS and BRAF wild-type, vulnerable patients aged ≥70 years with previously untreated mCRC. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results One hundred and eighteen patients were collected from 14 selected Italian centres. The median age was 75 (range, 70–85). Geriatric screening by G8 tool gave a score ≤ 14 in all patients. In total, 75 and 43 patients received FOLFOX or FOLFIRI, respectively, in combination with panitumumab (53%) or cetuximab (47%). The overall incidence of grade (G) 3–4 neutropenia was 11.8%, and for skin rash 11%. The most frequent adverse events were G1–2 skin rash (49.1%), G1–2 diarrhea (21.1%) and G1–2 nausea (17.7%). The ORR was 57.3%. Stable disease was observed in 29.1% of patients, with a disease control rate of 86.4%. With a median follow-up of 18 months, the median PFS was 10.0 months (95% confidence interval [CI]: 8.5–11.4), while the median OS was 18.0 months (95% CI: 16.0–19.9). No statistically significant difference was observed between the regimens in terms of ORR, PFS (p = 0.908), and OS (p = 0.832). Conclusion This study shows that with an appropriate design, including reduced doses, vulnerable older patients best tolerate chemotherapy when combined with anti-EGFR antibodies.

Purpose Valid prescribing indicators (PI) are needed for reliable assessment of prescribing quality. The purpose of this study is to describe the validity of existing PI for type 2 diabetes mellitus and cardiovascular risk management.Methods We conducted a systematic literature search for studies describing the development and assessment of relevant Pis between January 1990 and January 2009. We grouped identified PI as drug- or disease-oriented, and according to the aspects of prescribing addressed and the additional clinical information included. We reviewed the clinimetric characteristics of the different types of PI.Results We identified 59 documents describing the clinimetrics of 16 types of PI covering relevant prescribing aspects, including first-choice treatment, safety issues, dosing, costs, sufficient and timely treatment. We identified three types of drug-oriented, and five types of disease-oriented PI with proven face and content validity as well as operational feasibility in different settings. PI focusing on treatment modifications were the only indicators that showed concurrent validity. Several solutions were proposed for dealing with ease-mix and sample size problems, but their actual effect on PI scores was insufficiently assessed. Predictive validity of individual PI is not yet known.Conclusion We identified a range of existing PI that are valid for internal quality assessment as they are evidence-based, accepted by professionals, and reliable. For external use, problems of patient case-mix and sample size per PI should be better addressed. Further research is needed for selecting indicators that predict clinical outcomes. Copyright (C) 2009 John Wiley & Sons, Ltd.