Fatigue is a subjective experience that affects everybody. In healthy individuals, it can be considered a physiological response to physical or psychological stress. In people with specific diseases, however, fatigue often represents one of the most significant problems. Fatigue can be caused by many factors, both intrinsic to the patient and extrinsic, such as therapeutic interventions. This review, based on published studies, has been conducted with the aim of presenting a critical discussion of the available information on the characteristics, causes and potential treatments of fatigue in cancer patients receiving chemotherapy. The incidence of fatigue in these patients, the methods for measuring and evaluating fatigue, and possible therapeutic options are discussed. An appraisal of the toxicity of various chemotherapeutic agents is also presented. Although fatigue is now an ever more considered aspect of the toxicity of chemotherapy, it remains difficult to establish what standard should be used to make a quali-quantitative evaluation of this symptom. Furthermore, in the absence of a clear demonstration of the efficacy of some therapies, the management of cancer-related fatigue remains poorly defined (except for the treatment of anemia-related fatigue). New randomized clinical trials are necessary to indicate the best strategies for tackling this important problem.

No abstract

This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m À2 per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m À2 day À1 for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon's optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5 -16% and 2 -22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25 -101 weeks) for GEM and 26 weeks (range 16 -46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2 -65 weeks) and 18 weeks (range 4 -51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1 -101 weeks) and 30 weeks (1 -101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC.

Folfox-4 regimen is active and well tolerated in patients with advanced/metastatic gastric cancer.

This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX). One hundred and forty-three patients with measurable, non-resectable metastatic colorectal cancer were randomised in a multicentre study to receive TEGAFIRI (UFT 250 mg m À2 day days 1 -14, LV 90 mg day days 1 -14, irinotecan 240 mg m À2 day 1; q21) or TEGAFOX (UFT 250 mg m À2 day days 1 -14, LV 90 mg day days 1 -14, oxaliplatin 120 mg m À2 day 1; q21). Among 143 randomised patients, 141 were analysed (68 received TEGAFIRI and 73 TEGAFOX). The main characteristics of the two arms were well balanced. The most common grade 3 -4 treatment-related adverse events were neutropenia (13% of cases with TEGAFIRI; 1% in the TEGAFOX group). Diarrhoea was prevalent in the TEGAFIRI arm (16%) vs TEGAFOX (4%). Six complete remission (CR) and 19 partial remission (PR) were recorded in the TEGAFIRI arm (odds ratio (OR): 41.7; 95% confidence limit (CL), 29.1 -55.1%), and six CR and 22 PR were recorded in the TEGAFOX group, (OR: 38.9; 95% CL, 27.6 -51.1). At a median time follow-up of 17 months (intequartile (IQ) range 12 -23), a median survival probability of 20 and 19 months was obtained in the TEGAFIRI and TEGAFOX groups, respectively. Median time to progression was 8 months for both groups. TEGAFIRI and TEGAFOX are both effective and tolerable first-line therapies in MCRC patients. The employment of UFT/LV given in doublet combination is interesting and the presented data appear comparable to equivalent infusion regimens described in the literature. The safety profile of the two combinations also allows an evaluation with other biological agents such as monoclonal antibodies.