Incorporating standardized HRQL assessments in daily clinical oncology practice facilitates the discussion of HRQL issues and can heighten physicians' awareness of their patients' HRQL.

With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.

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Although both patients and oncologists seem willing to discuss a wide range of HRQL issues, communication regarding psychosocial issues may be hampered by competing expectations as to who should take the lead in initiating such discussions.

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CEM/MTX is a subline of human CCRF-CEM leukemia cells which displays >200-fold resistance to methotrexate (MTX) due to defective transport via the reduced folate carrier (RFC). CEM/MTX-low folate (LF) cells, derived by a gradual deprivation of folic acid from 2.3 M to 2 nM (LF) in the cell culture medium of CEM/MTX cells, resulted in a >20-fold overexpression of a structurally altered RFC featuring; 1) a wild type K m value for MTX transport but a 31-fold and 9-fold lower K m values for folic acid and leucovorin, respectively, relative to wild type RFC; 2) a 10-fold RFC1 gene amplification along with a >20-fold increased expression of the main 3.1-kilobase RFC1 mRNA; 3) a marked stimulation of MTX transport by anions (i.e. chloride); and 4) a G 3 A mutation at nucleotide 227 of the RFC cDNA in both CEM/MTX-LF and CEM/MTX, resulting in a lysine for glutamate substitution at amino acid residue 45 predicted to reside within the first transmembrane domain of the human RFC. Upon transfer of CEM/MTX-LF cells to folate-replete medium (2.3 M folic acid), the more efficient folic acid uptake in CEM/MTX-LF cells resulted in a 7-and 24-fold elevated total folate pool compared with CEM and CEM/MTX cells, respectively (500 versus 69 and 21 pmol/mg of protein, respectively). This markedly elevated intracellular folate pool conferred a novel mechanism of resistance to polyglutamatable (e.g. ZD1694, DDATHF, and AG2034) and lipophilic antifolates (e.g. trimetrexate and pyrimethamine) by abolishing their polyglutamylation and circumventing target enzyme inhibition.

Summary This study examined the usefulness of caregiver ratings of cancer patients' quality of life (QOL), an issue of relevance to bot h adequate patient care and to the possible use of proxy QOL raters in clinical studies.We compared QOL ratings of 90 cancer pat ients receiving inpatient chemotherapy with those provided by their significant others (most often the spouse), physicians and nurses . During patients' scheduled appointment for receiving chemotherapy on a clinical ward, all raters completed independently the Dartmouth COOP Functional Health Assessment charts/WONCA, an instrument developed by a cooperative group of primary care physicians to briefly assess a core set of seven QOL domains (physical fitness, feelings, daily and social activities, overall health, pain and quality of l ife) by single items with five response options. With few exceptions, mean scores of the proxy raters were equivalent or similar to those of the pat ients. Most patient-proxy correlations varied between 0.40 and 0.60, indicating a moderate level of agreement at the individual level. Of a ll comparisons made, 41% were in exact agreement and 43% agreed within one response categor y, leaving 17% more profound patient-proxy discrepancies. Disagreement was not dependent on the type of proxy rate r, or on raters' background characteristics, but was inf luenced by the QOL dimension under consideration and the clinical status of the patient. Better patient-proxy agreement was observed for m ore concrete questions (daily activities, pain) and for patients with either a very good (ECOG 0) or poor (ECOG 3) performance status. The r esults indicate that both significant others and health care providers can be useful sources of information about cancer patients' QOL.

Despite increasing recognition of the importance of maintaining patients' HRQL as a goal of palliative treatment, the amount of patient-physician communication devoted to such issues remains limited and appears to make only a modest contribution, at least in an explicit sense, to the evaluation of treatment efficacy in daily clinical practice.