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Does Palliative Chemotherapy Palliate? Evaluation of Expectations, Outcomes, and Costs in Women Receiving Chemotherapy for Advanced Ovarian Cancer

From the Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.

Address reprint requests to Amit M. Oza, MD, Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Toronto, Ontario, M5G 2M9, Canada; email: amit.oza{at}uhn.toronto.on.ca

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: The value of palliative chemotherapy in women with refractory and recurrent ovarian cancer is difficult to quantify, and little is known about patient expectations from these treatments. We evaluated in the current prospective study patient expectations, palliative outcomes of chemotherapy, and the inherent resource utilization in patients undergoing second- or third-line chemotherapy for recurrent or refractory advanced ovarian cancer.

METHODS: The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ C30) and Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaires were used to assess palliative benefit and an in-house questionnaire was used to gauge patient expectations. The minimal clinically important difference (MCID) was calculated by asking women to make a global rating of change and correlating this to the EORTC QLQ C30. Resource use was recorded and costs were calculated.

RESULTS: Twenty-seven patients were accrued. Objective response was documented on seven of 27. The median survival was 11 months. Sixty-five percent of women expected that chemotherapy would make them live longer and 42% that it would cure them. After two cycles, quality-of-life (QL) improvement was seen particularly in global function (11 of 21) and emotional function (13 of 21) with EORTC QLQ C-30. Improvement was sustained for a median of 2 and 3 months, respectively, in these categories. The MCID was calculated to be 0.39 on a seven-point scale for physical function and 0.13 for global function. The mean total cost per patient for the study period was Can $12,500.

CONCLUSION: Patient expectations from these treatments are often unrealistic. Although objective responses are low, active palliation with chemotherapy is associated with substantive improvement in patients’ emotional function and global QL, with overall costs that seem relatively modest.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
THERAPY FOR refractory and recurrent ovarian cancer is directed toward palliation of symptoms and maintenance of quality of life (QL). Results of studies of chemotherapy in this group of patients using conventional end points such as survival, time to progression, and response rate are generally disappointing. Women who recur or progress more than 6 months after platinum-based chemotherapy are usually retreated with a platinum-based regimen, with response rates ranging from 27% to 60% and median survival of approximately 1 year.^1-4 For platinum-resistant patients, reported response rates range from 12% to 30%, with a short median survival of approximately 9 months using a different chemotherapy regimen.^5-13 Toxicity associated with some palliative treatments can be important, and resource implications are considerable. As recently reported, the mean cost per patient from initiation of second- or third-line chemotherapy until death was estimated to be Can $53,000, with 45% of this total cost attributable to chemotherapy.¹⁴ In these times in which it is becoming increasingly necessary to rationalize health services, it is important to factor in the resource implications of therapy.

Most of the existing trials place emphasis on response rate, which per se is not a direct measure of patient benefit. Justification for using such treatments for palliation would require that they offer some improvement in the QL of treated patients.

Few studies have reported data on the effect of chemotherapy on the QL of patients with ovarian cancer. De Haes et al¹⁵ showed that there was no correlation between toxicity and QL in advanced ovarian cancer. Of note, no study has compared chemotherapy to best supportive care in this situation.

It is difficult to quantify the benefits of palliative chemotherapy. In addition, there is little information on what is expected by patients from these treatments. Slevin et al¹⁶ have reported that the majority of patients offered chemotherapy will accept for only 1% chance of cure, and at least 40% would have accepted if it could prolong their life by only 3 months, whereas doctors, nurses, and age-matched healthy people were much less willing to accept chemotherapy if asked the same question. Gough et al¹⁷ reported that there was no correlation between patients feeling that chemotherapy was worthwhile and objective response therapy for metastatic gastrointestinal cancers.

To better understand the implications of palliative chemotherapy for patients with recurrent or refractory ovarian cancer, we designed this pilot study to prospectively evaluate patient expectations, QL, and patient perceptions of benefit in women undergoing second- or third-line chemotherapy for ovarian cancer. We also evaluated more conventional end points of toxicity, response rate, duration of survival, and described the costs associated with these therapies from the perspective of the provincial health care provider.

	METHODS

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A prospective study was undertaken at Princess Margaret Hospital and at the Toronto General Hospital. Patients with histologically confirmed epithelial ovarian cancer who had previously received systemic therapy with a cisplatin- or carboplatin-based regimen were entered onto the study if they were about to start a second- or third-line chemotherapy regimen for progressive or recurrent disease. They had to understand written and spoken English or French to be able to complete questionnaires.

Women were excluded if there was an established underlying psychiatric or affective disorder, if geographic inaccessibility prevented treatment and follow-up in one of the participating centers, and in the case of failure to give informed consent. The choice of chemotherapy regimen and treatment duration was determined by the treating physician, according to his/her standard practice. In general, a platinum-based regimen was used in patients who already responded to first-line cisplatin and recurred with an interval free of chemotherapy of more than 6 months. Other drugs were used in patients considered resistant to cisplatin.

History and physical examination were performed at baseline and every 3 to 4 weeks at each cycle of chemotherapy up to two follow-up visits, the first one being 4 weeks after the end of chemotherapy. Complete blood cell count, creatinine, liver function, and CA-125 were done at baseline, before each cycle of chemotherapy, and on follow-up visits. Selective imaging studies were done at baseline and repeated after two or three cycles of chemotherapy according to the treating physician and depending on the site of measurable disease.

Clinical response was confirmed on two occasions, 3 or 4 weeks apart. Standard criteria were used to define response. Toxicity was measured at each cycle of chemotherapy using the National Cancer Institute of Canada Clinical Trials Group common toxicity criteria. Duration of survival was measured from the time of entry in the study until death.

Patient Expectations
To evaluate patient expectations, a questionnaire was administered at baseline, before starting the first cycle of chemotherapy. All patients had met with their oncologist, who had explained that the primary goal of chemotherapy would be to palliate symptoms and that in this setting, treatment would not be curative.

Patients were asked in a questionnaire whether they thought that chemotherapy would make them feel better, delay further problems, make them live longer, cure their disease, or make them feel worse. The potential responses were in the form of a four-point scale: not at all, a little, quite a bit, and very much.

They were also asked the following: Overall, how do you think chemotherapy will make you feel? The response was in the form of a seven-point scale ranging from much worse to much better.

Patients were also asked whether they thought that chemotherapy would be very worthwhile, moderately, a little, or not at all. This last question was asked at baseline and repeated after completion of chemotherapy.

QL
The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30 (EORTC QLQ C-30) core and the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaires were used for measurement of QL in this study. Both are internationally validated questionnaires and have been used on multiple studies. They are composed of multi-item scales in the form of Likert and yes/no questions assessing physical, role functioning, cognitive, emotional, and social aspects. The EORTC QLQ C-30 also includes symptom measures and a global health and QL scale. The ovary version of the FACT offers additional questions more specific to ovarian cancer.

Patients completed the questionnaires themselves in the presence of the clinical trial nurse before initiation of chemotherapy, and this was used as a baseline measurement. They subsequently completed the questionnaires at each visit before the next course of chemotherapy and before meeting with their physician. To have a better representation of the QL between cycles of chemotherapy, patients were also given a questionnaire that they completed at home 1 week after each treatment, which should more accurately reflect the side effects from chemotherapy. The clinical trials nurse phoned the patients 1 week posttreatment to remind them to fill out questionnaires and to ask about side effects. After completion of chemotherapy, patients continued to fill out questionnaires for the next two follow-up visits.

The scoring procedure for the EORTC QLQ C-30 and FACT-O are well defined and were followed. For the EORTC QLQ C-30, the raw scores for the individual items within a scale are first summed and divided by the number of items within the scale. This score is then linearly transformed to range from 0 to 100. The FACT-O score is calculated for each subscales, then the scores are added to obtain a total score, the maximum total score being 160.

The Minimal Clinically Important Difference
To determine whether the magnitude of QL changes that were observed is clinically meaningful or not is of obvious importance. A way of objectively evaluating this is to calculate the minimal clinically important difference (MCID). This is defined as the smallest difference in score in the domain of interest that the patient perceives as beneficial and that would mandate a change in patient’s management.¹⁸ In studies reported by Jaeschke et al¹⁸ and Juniper et al¹⁹ in patients with different diseases and different questionnaires, a within-subject change in score of 0.5 (7%) on a seven-point scale was measured as the MCID. To investigate the MCID in the present study, we adopted the methodology of Jaeschke and Juniper and added two questions. Patients had to make a global rating of change compared with their previous visit in their physical condition and QL. The two questions read as follows: (1) Please indicate whether overall there has been any change in your physical condition since the last time you saw us by choosing one of the following options: -3, much worse; -2, moderately worse; -1, a little worse; 0, no change; 1, little better; 2, moderately better; 3, much better. (2) Please indicate whether overall there has been any change in your QL since the last time you saw us by choosing one of the following options: (same choice of answers as question 1). Answers were then correlated to the difference in score of the corresponding questions (item 29 and 30) of the EORTC QLQ C-30 for which a mean was calculated. The mean difference in score corresponding to choice of answer -1 and 1 were considered as MCID.

Costs
Resources used in patient treatment were recorded prospectively. Attributable costs were calculated at the end of the study and determined in 1994 Canadian dollars (US $1.00 = Can $1.40) and are reported rounded to the nearest 100 dollars. The methodology and values have been reported in a previous study.¹⁴ Costs were divided into the following major categories: inpatient, outpatient, chemotherapy drugs, nonchemotherapy drugs, radiotherapy, laboratory tests, and diagnostic imaging. The costing period extended from the entry into the study until the end of study date, ie, two follow-up visits after the end of chemotherapy.

Inpatient Cost and Outpatient Cost
The hotel-approximation method described by Hull et al²⁰ was used. This method makes the assumption that certain "hotel" costs are the same for each inpatient day or each outpatient visit independent of the reason for admission or for visit. The costs of administration, housekeeping, security, laundry, nutrition, medical records, and maintenance fall into this category. The proportion of these hotel costs attributable to inpatient as compared with outpatient services was estimated using an appropriate allocation unit for each item based on 1994 fiscal year financial report. To these hotel costs were added the individualized costs of medical care for each patient, including nursing, ward supply, physician services, and special procedures.

Laboratory Tests and Diagnostic Imaging Costs
These costs were calculated from the Ontario Health Insurance Plan Fee Schedule, which provides a unit system that takes physician fee, technician time, and other costs into account.

Drug Costs
The costs of drugs prescribed were based on the cost to the hospital of purchasing the drugs using computerized database and price lists. The costs of preparation by the pharmacy staff based on average preparation time and salaries were added.

Radiotherapy Costs
The hotel approximation method was also used, including salaries of staff involved in direct patient care, professional fees, and salaries of radiation oncologists, salaries of support and technical staff, costs of supplies, and depreciation cost of major equipment.

Statistical Methods
The main measure for QL used to evaluate change with treatment was the global health status/QL of the EORTC QLQ C-30. Results from other subscales and FACT-O were considered as secondary end points and were reported descriptively.

The QL results were also analyzed to determine changes from baseline after two cycles of chemotherapy using Wilcoxon signed rank test. QL scores compared with baseline were assessed as well. Any improvement detectable by the questionnaires was considered improvement. The EORTC QLQ C-30 is composed of two- to seven-point scales. The difference in score detectable, therefore, cannot be lower than 8.3, whereas with the FACT-O, it cannot be lower than 1.0, the maximum total score for the FACT-O being 160. All patients accrued were included in the analysis. QL questionnaires not completed during chemotherapy because of progression of disease or death were considered as missing. It was assumed that if the QL improved in less than 20% of patients, the chemotherapy would be considered not worthwhile to improve QL. Duration of survival was measured from time of entry onto the study using Kaplan-Meier method. A sensitivity analysis was performed to assess the impact of changes in the cost of individual categories on total cost. This was done by calculating the percentage of change in the cost of each category that would be required to change total cost by 1%.

	RESULTS

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Patients
Twenty-seven eligible patients commenced second- or third-line chemotherapy between July 1994 and October 1996. All consecutive women satisfying inclusion criteria were approached. The majority agreed to participate. At the time of the analysis, one patient was still on treatment and one patient didn’t have any QL record. All patients who had QL questionnaires completed at least up to the time of the analysis (example up to cycle 2) were included regardless of whether they were still on treatment. Two patients had only one QL questionnaire at baseline, and they were considered as having deteriorated. Patient characteristics are listed in Table 1. The median age was 55 years and the distribution of histologic subtypes was similar to that described in the literature, with a predominance of serous type. Most had International Federation of Gynecology and Obstetrics stage III disease at initial presentation. All women had received carboplatin- or cisplatin-based chemotherapy previously. The majority of women were entered onto study on the second line of chemotherapy. Carboplatin- or cisplatin-based regimen and paclitaxel were the most frequently prescribed treatments. Patients received a median of three cycles.

Survival
At the time of analysis, 12 women were alive and 15 had died. The median survival from entry onto the study was 11 months.

Toxicity
Thirteen and four patients experienced grade 3 or 4 toxicity, respectively, excluding alopecia. There were a total of 77 episodes of grade 3 and 4 toxicity. Grade 4 toxicity consisted of two episodes of severe neutropenia and two episodes of gastrointestinal toxicity.

Patient Expectations
Of note, the majority of women expected that chemotherapy would make them feel better (58% quite a bit/very much), would delay further problems (62%), and make them live longer (65%). Interestingly, 42% thought that chemotherapy would have a moderately high or high likelihood of curing their disease. Only a few patients expected they would feel worse (quite worse or much worse). All women thought chemotherapy would be at least moderately worthwhile at entry onto the study (three patients didn’t answer).

After the end of treatment, women were asked whether they felt this had been worthwhile. Of the 11 women who answered, five felt it was very worthwhile, one moderately worthwhile, two little worthwhile, and three felt that it was not worthwhile. Of those who answered very or moderately worthwhile, all had a partial or a complete response. Those who answered this was not worthwhile had either stable or progressive disease. Additionally, many patients who had clinical progression did not complete this questionnaire. In fact, of all those with progressive disease, only five answered this question.

QL
There was considerable variation in baseline QL scores. Several patterns of change in these scores were apparent. The QL data were analyzed to assess overall change and change from baseline to score after two cycles of treatment.

Quantitative assessment of change in QL scores from baseline after cycle 2. This was chosen because in clinical practice, most oncologists use a minimum of two cycles of therapy to assess whether the treatment is helping, and decide to continue with therapy or to stop/change treatment.

The results of the QL questionnaire precycle 3 or at first follow-up visit compared with baseline are presented in Table 2. There were 21 patients who completed two cycles of chemotherapy and either had the third cycle or a follow-up visit so they were available for this analysis. After two cycles of therapy, there was improvement in more than 20% of patients in the majority of the domains, particularly emotional function and global health. Improvement in symptom control, particularly pain and nausea and vomiting, was also apparent in more than one half of the patients. The responses to both EORTC and FACT-O questionnaires showed consistency with each other. The level of improvement was never lower than 8% with the EORTC questionnaire and one point with the FACT questionnaire (Table 2).

For physical function, answers to question 29 EORTC QLQ C30, from the seven-point scale (0-6), were measured as follows: "a little better" translated as a change of 0.39 or 6.6%; "a little worse" corresponded to a change of -0.36 or 6%. For QL, answers to question 30 EORTC QLQ C30, from the seven-point scale as follows (0-6): "a little better" translated as a 0.13 point change or 2.2% change; "a little worse" correlated to a -0.42 change or 7%.

An example of the scores obtained and distribution of answers is given in Table 4. The mean improvement in global health status/QL subscale of the EORTC QLQ C-30 score (questions 29 and 30) for women who improved after two cycles was 33%, ranging from 8.3% to 75% improvement, compared with baseline.

	DISCUSSION

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This study sheds light on the difficult area of palliation using systemic therapy. Although systemic treatment is offered commonly to palliate and treat patients where cure is unlikely, there is little information about the value of such treatment from the patients’ perspective.

The importance of patient expectations in the context of evaluation of QL is stressed by Wan et al,²¹ who demonstrated that the discrepancy between what patients expect and what actually occurs with treatment is a significant predictor for every dimension of health-related QL. Narrowing this gap seems to be associated with better QL scores. Our evaluation of patient expectations yielded surprising results. Forty-two percent of this group of women thought that chemotherapy would have a moderate to high chance of curing their disease. From these results, it seems that many patients accept chemotherapy for reasons that are possibly quite different from those of the physicians who recommend it. These very high and unrealistic expectations may be related to patients’ way of coping with stress and possibly not wishing to acknowledge the prospect of dying of disease. Another possible explanation is that it could be related to poor doctor-patient communication. In this study, the physicians had met the patients and explained the goals of palliative treatment, emphasizing that this would not be curative, and also presented patients with a written consent and information sheet that stressed the palliative nature of this study. Despite this, there was a discrepancy between what was thought to have been explained and what was heard. A method to improve patient understanding may be to provide personalized letters to patients after consultation or even a videotape of the consultation as reported by Tattersall et al.^22,23

Despite a relatively high level of toxicity and rather modest objective response, an improvement in QL was observed in a significant proportion of patients. After two cycles of chemotherapy, 52% of patients noted an improvement in their global health status/QL subscale of the EORTC QLQ C-30, while the global score of the FACT-O was improved in 43% of women. We decided to assess change in QL after cycle 2, as pragmatically, the majority of patients complete two cycles before clinical reassessment and decision to continue therapy. Of patients who continue with therapy, particularly beyond cycles 3 and 4, there is a preponderance of responders, and therefore the QL response might reflect a bias toward patients who are doing well. The evaluation of patterns of improvement and duration of improvement also permitted us to note that a substantial proportion of patients improved and that this improvement could be sustained despite the side effects of chemotherapy, which were mainly reported on day 8 questionnaires. In the case of global health status QL sub-scale and emotional function subscale of EORTC QLQ C-30, a sustained improvement occurred in 43% and 52%, respectively, lasting for a median of 64 days and 107 days, respectively. The same trends were found with the FACT-O.

These QL results suggest that palliative chemotherapy in ovarian cancer can palliate a substantial proportion of patients. Looking at the different subscales, the greatest improvement was seen in emotional function, which also lasted longest. This needs to be evaluated more thoroughly to determine how large a role the placebo effect plays in this improvement. Is there a possibility that other less intensive interventions, for example group meetings or talking, might also improve emotional function and thus offer some form of palliation without chemotherapy? Traditionally, palliation means reduction of physical symptoms and not necessarily improvement of emotions. We feel that palliation should encompass physical and emotional symptoms. During palliative treatment, the aim is for overall improvement in the person’s well-being. In addition to the emotional aspect, many symptom subscales in this study showed clear improvement in physical symptoms, particularly nausea, vomiting, pain, and loss of appetite.

It is important to emphasize that the population studied here is a select one and conclusions may not be generalizable. As patients had to understand English or French and be able to fill questionnaires, this may have resulted in socioeconomic level selection bias. However, it is difficult to make specific inferences regarding bias or sociodemographic characteristics, as the sample size is small. This would certainly be best evaluated in a larger prospective trial.

This pilot study has also explored the different aspects of interpreting QL score results. Obtaining data on QL during a study is relatively easy but interpreting these data and presenting them in a way that has some clinical meaning is not always obvious. Our exercise to determine the MCID added patients’ perspectives to QL instrument scores. It is interesting to note that the results obtained are similar to what has been published in the literature, despite the differences in type of disease/treatment and questionnaires. We found that the smallest difference in score perceived by patients as benefit was 6.6% on a seven-point scale for the physical function and 2.2% for the global QL question. Previous studies using the Chronic Heart Failure Questionnaire and the Asthma QL Questionnaire found that a within subject, change in score of 0.5 (7%) on a seven-point scale represented the MCID.^18,19 It seems that the minimal difference perceived by patients as being significant is relatively low. Additionally, in the present study, the smallest improvement in score after two cycles of chemotherapy was above the level of MCID obtained. This was demonstrated only for the global health status/QL subscale of the EORTC questionnaire, because other subscales of EORTC QLQ C-30 and FACT-O are not seven-point scales. This exercise reconfirms that patients will accept systemic therapy for relatively small benefit, as initially observed by Slevin et al.¹⁶ It is encouraging to note that the minimum improvement with systemic chemotherapy exceeds this MCID.

The feeling that chemotherapy has been worthwhile seems to correlate with the objective tumor response in this study, but it is difficult to correlate with QL results. We are aware that there is an important bias in that question because only 11 of 27 patients answered. In fact, the numbers in our study are too small to make conclusions but do raise an important question: what is more important to patients, tumor response or QL improvement? One difficulty with the assessment of worthwhileness at the end of therapy is that there are many patients who are too ill to be able to answer the questionnaire. Patients who are well enough to fill the questionnaires are likely to be a select group who have done well with treatment and who probably find their chemotherapy to have been worthwhile.

The study also provides an estimate of costs of caring for women with recurrent or refractory ovarian cancer during one line of chemotherapy. The overall cost was relatively modest, with a mean cost of Can $12,500. The two major components were hospitalizations and chemotherapy. They accounted for 37% of total cost each. The proportional cost of chemotherapy seems relatively high and is higher still if all costs related to chemotherapy administration are added. Including the cost of hospitalizations related to chemotherapy delivery and its complications increases the proportion of total cost related to chemotherapy to 46%. This high proportion of total cost related to chemotherapy is predictable, because the costing period specifically covered the period when patients were receiving chemotherapy. In most of the cases, terminal care, which accounts for a large proportion of costs, was not included. In our previous study, we calculated the costs in the same type of population but started costing from initiation of palliative second- or third-line chemotherapy and continued until death, with a total cost of Can $53,000 dollars per patient.¹⁴ In this previous study, we found a higher proportion of cost due to hospitalizations (61%) and a higher proportion of hospitalization for chemotherapy delivery (32%). This difference reflects the terminal care included in the first study but not in the present one. Another factor is a shift toward outpatient administration of chemotherapy, which has become apparent in more recent years.

It is important to realize that costs reported in this study do not reflect cost of one type of chemotherapy but cost of different possible regimens used in patients with recurrent or refractory disease. For example, paclitaxel accounted for 30% of all regimens used in the study and carboplatin or cisplatin associated with cyclophosphamide accounted for another 30%. The sensitivity analysis showed that a small increase in cost of chemotherapy is needed to change the total cost by 1%. Therefore, an increase in drug costs could significantly increase total costs.

In total however, the mean cost of one line of chemotherapy in this group of patients does not seem to be high and as we found that a good proportion of patients had improvement in their QL, there is a possibility that such palliative treatment could be cost effective. However, to be able to establish the cost effectiveness, a randomized trial comparing chemotherapy and best supportive care would be needed. Until this type of randomized trial is done, the present pilot study supports the use of second- or third-line chemotherapy in patients with advanced ovarian cancer who seem to benefit with improvement in their QL. It should also be noted that good palliative care itself is associated with significant costs. Emanuel and Emanuel²⁴ looked at the economics of dying, reporting the average hospital cost for dying patients to range between US $56,000 to $62,000, depending on whether patients had an advance directive. However, they felt that it would be difficult to substantially reduce the percentage of health care expenditure in patients who did have an advanced disease, because humane care at the end of life is labor-intensive and therefore expensive. Our studies would tend to support this view. Palliative chemotherapy does palliate, and the cost of doing so is not unreasonable. However, it is evident that chemotherapy-related costs begin to escalate with multiple lines of therapy.

This study also highlights the fact that patients expectations from these treatments are high and often at odds with the framework of recommendations which led to those very treatments. It is important to evaluate in more detail these differences. The two questions that need to be asked for the future are as follows: (1) How often does palliative chemotherapy meet patient expectations? (2) In a palliative setting, what outcome do patients really value more: response of tumor, improvement in QL, or relief of symptoms? This would allow the definition and selection of appropriate end points for future palliative studies. This should be explored in a larger study, prospectively evaluating patient expectations with outcomes such as response rate and QL in the context of palliative treatment. Costs could also be evaluated in relation to minimal clinically significant changes. Ideally, this study would standardize the delivery of information to patients, perhaps with additional counseling and additional written information. With a larger sample size, the impact of treatment and site of origin of disease could also be investigated—for example, patients with lung cancer versus patients with advanced ovarian cancer. The outcomes in relation to sociodemographic characteristics could also be explored. A large study would also assess the impact of chemotherapy toxicity versus QL. The ultimate challenge is to narrow the gap between patient expectations and outcome by improving therapeutic efficacy and effective physician-patient communication.

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
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Submitted January 26, 1999; accepted October 24, 2000.

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