BACKGROUND Quality‐of‐life (QoL) issues have become increasingly important as the number of newly diagnosed patients with cancer increases and survival improves. In 1983, Coates et al. reported a survey of patient perceptions of the side effects of cancer chemotherapy and showed the importance of including patient feedback for the accurate assessment of QoL (Eur J Cancer Clin Oncol. 1983;19:203–208.). The authors carried out a similar survey in 100 patients with cancer with the objectives of 1) investigating the changes in patient perceptions that have occurred and 2) evaluating the impact of new treatments on the profile of chemotherapy side effects among patients receiving anticancer drugs. METHODS One hundred patients attending the outpatient Medical Oncology Department of the Pitié Salpêtrière Hospital Group were surveyed between August 1998 and February 2000 by trained interviewers who were blinded to the patients' treatment. Patients identified all side effects associated with their treatment using a set of 45 cards that named physical side effects (Group A) and a set of 27 cards that named nonphysical side effects (Group B), and the patients ranked these side effects according to severity. The top 5 cards from each group were then combined, and the resulting 10 cards were rated again by severity, regardless of group. Results were analyzed for the entire cohort and for demographic, social, and clinical subgroups. RESULTS The participants included 65 women and 35 men; the most common malignancies were breast carcinoma (40 patients), gastrointestinal carcinoma (19 patients), lung carcinoma (7 patients), and ovarian carcinoma (9 patients). Patients rated affects my family or partner as the most severe side effect, alopecia was second, and fatigue was the third most severe. Effects on work or home responsibilities, effects on social activities, and loss of interest in sex were ranked fourth, fifth, and sixth, respectively. The results contrasted with those of Coates et al., in which affects my family or partner was ranked 10th, and fatigue was ranked 8th. CONCLUSIONS Patient perceptions of the side effects of cancer chemotherapy have changed markedly. In the current study, fatigue and psychosocial QoL concerns predominated, compared with emesis, nausea, and negative reactions to the treatment visit in the original survey. The current findings are consistent with the progress that has been made in reducing certain chemotherapy‐associated toxicities. Fatigue, however, although it often is related to anemia and is treatable with recombinant human erythropoietin, remains a major concern. The emotional, social, and sexual consequences of cancer treatment present continuing challenges in efforts to optimize QoL and to develop effective supportive care. Cancer 2002;95:155–63. © 2002 American Cancer Society. DOI 10.1002/cncr.10630

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We investigated the degradation and racemization of zopiclone (ZOP) enantiomers in plasma and partially aqueous solutions (ethano1:phosphate buffer). Degradation and racemization increased with increasing pH and temperature. Degradation products were identified by means of mass spectrometry, which revealed hydrolysis of the carbamate function and opening of the pyrrolidone ring. In plasma, neither degradation nor racemization occurred after 6 months of storage at -20°C and subsequent extraction. KEY WORDS: chirality, cyclopyrrolone, isomers, racemization, stability, zopiclone Zopiclone (ZOP) is a c h a l cyclopyrrolone ( Fig. 1) with hypnotic properties. It is administered therapeutically as a racemic mixture. ' The racemate has been extensively studied, and several analytical methods based on liquid chromatography or gas chromatography have been proposed for its determination in plasma. 2-7 Two chiral methods have been reported for the study of ZOP enantiomers in plasma and urine, using liquid chromatography with spectrofluorimetric detection. ' ,' It has recently been demonstrated that ZOP pharmacokinetics are stereoselective: higher plasma concentrations of the (+) enantiomer were observed following oral administration of the racemic mixture to humans.Enantiomers of certain chiral compounds, such as oxazepam, 11*12 thalidomide, l3 hyoscyamine, l 4 scopolamine, l4 and thymidine glycol, l5 undergo racemization in vitro in aqueous or partially aqueous solutions. It has been shown that compounds such as thalidomide and nonsteroidal antiinflammatory agents can also racemize in vivo. 13*16 In vitro or in vivo racemization may complicate stereoselectivity studies. When studying the stereoselective kinetics of a chiral compound, it is essential to prove that racemization does not occur during storage or treatment of biological samples.Given the presence of a carbamate function on the asymmetric carbon, we investigated the stability and racemization of ZOP enantiomers and the racemic mixture in conditions usually employed for the study of ZOP pharmacokinetic stereoselectivity . EXPERIMENTAL Materials and MethodsSemipreparative chromatography. The HPLC system for semipreparative enantiomer separation consisted of an LC-6A pump (Shimadzu, Touzart et Matignon, Vitry, France), a Rheodyne 7125 injection valve equipped with a 1 ml loop, a Lambda-Max Model 480 UV detector (Waters, Mdford, USA), and a C-R6A integrator (Shimadzu). The column was a semipreparative Chiralcel OD (10 x 250 mm) (Daicel, J.T. Baker France, Paris, France). A 300 ~1 aliquot of freshly prepared ruc-ZOP solution in ethanol (2 mg/ml) was injected into the semipreparative column and eluted with ethanokhexane (6040, v/v) at a flow rate of 2 mumin.Mobile phase fractions containing (-)-ZOP or (+)-ZOP were separately evaporated to dryness under nitrogen. After reconstitution with ethanol, the purity of the separated enan-

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