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MELOSKY et al.
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CURRENT ONCOLOGY—VOLUME 15, NUMBER 6
MEDICAL ONCOLOGY
Copyright © 2008 Multimed Inc.
ABSTRACT
Background
Epidermal growth factor receptor tyrosine kinase in-
hibitors (EGFR-TKIs) and chemotherapy have both dem-
onstrated efficacy in recurrent metastatic
non-small-cell lung cancer (NSCLC) following failure
of first-line platinum-based chemotherapy. Although the
3 available therapeutic agents—docetaxel, erlotinib,
and pemetrexed—have significantly changed the treat-
ment landscape for recurrent NSCLC, the optimal se-
lection of second- and third-line therapy has not been
established. This practice review examines the out-
comes in clinical practice of using second-line erlotinib
followed by third-line chemotherapy in the treatment
of recurrent metastatic NSCLC.
Methods
We conducted a retrospective review of NSCLC patient
charts at three Canadian institutions. Patients with re-
current NSCLC who had received second-line erlotinib
therapy followed by third-line chemotherapy were se-
lected by census. A chart review assessed key out-
comes that included time to progression (TTP),
response, and change in performance status. Outcomes
for specific patient subgroups were also examined.
Results
We identified 35 patients for this retrospective prac-
tice review. First-line platinum-doublet therapy dem-
onstrated a mean TTP of 6.6 months and a 46% overall
response rate (15 partial responses and 1 complete re-
sponse). Second-line treatment with erlotinib produced
the highest mean TTP of all lines of therapy (9.2 months)
and an overall response rate of 40% (all being partial
responses). In the third-line setting, in which most pa-
tients received docetaxel, the mean TTP was 4.3 months
and the overall response rate was 18% (all being par-
tial responses). Subgroup analysis showed that all pa-
tient subgroups demonstrated benefit from second-line
erlotinib treatment; improved benefit was observed in
Retrospective practice review
of treatment of metastatic
non-small-cell lung cancer
with second-line erlotinib
B. Melosky
MD
,* J. Agulnik
MD
,
†
and
H. Assi
MD‡
patients who developed rash, in female patients, in never
smokers, in Asian patients, in patients with positive EGFR
status, and in patients with adenocarcinoma histology.
Conclusions
For patients with advanced NSCLC who progressed fol-
lowing first-line platinum-based chemotherapy, the data
demonstrate that second-line EGFR-TKI treatment is
efficacious and well-tolerated and that it does not ap-
pear to diminish the benefit of third-line chemotherapy.
KEY WORDS
Non-small-cell lung cancer, NSCLC, epidermal growth
factor receptor, EGFR, tyrosine kinase inhibitor, TKI,
erlotinib, second-line, retrospective practice review
1. INTRODUCTION
Lung cancer remains the leading cause of cancer-re-
lated death in both women and men in Canada and
throughout the world 1,2. The estimated 24,000 Cana-
dians who will be diagnosed with lung cancer in 2008
face a 5-year relative survival rate of 15% 1. Current
survival rates reflect modest advances in anticancer
therapies, considering the 5% average 5-year survival
rate of the 1960s.
Non-small-cell lung cancer (NSCLC) is the most
common and deadly form of lung cancer 3. The cur-
rent standard of care for patients with locally advanced
or metastatic NSCLC and adequate performance status
(PS) involves up to 3 lines of systemic therapy. Plati-
num-based combination chemotherapy is recognized
as the first-line standard of care in NSCLC 4. Upon fail-
ure of first-line therapy, 3 treatment options currently
exist for second- and subsequent-line therapy (Table I).
Docetaxel (Taxotere: Sanofi-Aventis Canada, Laval,
QC) was the first cytotoxic agent approved for the sec-
ond-line treatment of advanced NSCLC based on phase
III trials showing a longer survival than that seen with
with best supportive care (BSC) 6. Erlotinib (Tarceva:
Hoffmann–La Roche Ltd., Mississauga, ON), an epi-
dermal growth factor receptor tyrosine kinase inhibitor
SECOND-LINE ERLOTINIB IN NSCLC
CURRENT ONCOLOGY—VOLUME 15, NUMBER 6
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280
(EGFR-TKI), was approved in Canada in 2005 as
monotherapy for the treatment of patients with meta-
static NSCLC after failure of at least 1 prior chemo-
therapy regimen 11. Erlotinib demonstrated survival
improvement in addition to control of the most distress-
ing lung cancer symptoms and improvement in quality
of life (QOL). The phase III JMEI trial 7 (n = 571) dem-
onstrated that the clinical efficacy of pemetrexed
(Alimta: Eli Lilly Canada, Toronto, ON) was equiva-
lent to that of docetaxel, therefore making pemetrexed
a third option for therapy in recurrent NSCLC.
Epidermal growth factor receptor is overexpressed
in approximately 80% of NSCLC cases, making it an
ideal therapeutic target 12. As an EGFR-TKI, erlotinib
competes with ATP for the catalytic binding site of the
EGFR tyrosine kinase inside tumour cells, thus inhibit-
ing EGFR autophosphorylation and subsequent down-
stream signalling 13. Agents that target EGFR spare
healthy cells by selectively inhibiting specific pathways
involved in tumour growth and progression, resulting
in a favourable safety profile as compared with chemo-
therapeutic agents 14.
Several trials have demonstrated the activity of
EGFR-TKIs in recurrent NSCLC. The phase III National
Cancer Institute of Canada BR.21 trial 8 ( n = 731) com-
pared erlotinib with BSC in patients with advanced NSCLC
who had received 1 or 2 regimens of chemotherapy and
who were not eligible for further chemotherapy. Half of
the patients in the trial were treated with erlotinib as
second-line therapy, and half received erlotinib as third-
line therapy. As compared with BSC, treatment with
erlotinib resulted in significantly longer overall survival
[6.7 months vs. 4.7 months; hazard ratio (HR): 0.70; p <
0.001] and significantly higher progression-free survival
favouring erlotinib (2.2 months vs. 1.8 months; HR: 0.6;
p < 0.001). Patients who received erlotinib also demon-
strated significantly longer stability of their lung can-
cer-related symptoms (dyspnea, pain, and cough),
superior QOL, and improved physical function as com-
pared with patients in the placebo arm.
The subgroups with a greater likelihood of a re-
sponse to erlotinib have been widely catalogued, but a
multivariate analysis revealed that a non-smoking his-
tory was the only significant independent predictor of
a survival effect with erlotinib 15. Never smokers re-
ceiving erlotinib had a significantly higher survival rate
than did patients in the placebo arm (HR: 0.4; p < 0.01).
Docetaxel, erlotinib, and pemetrexed have signifi-
cantly changed the treatment landscape for advanced
NSCLC, but the optimal selection of second-line (and
subsequent third-line) therapy has yet to be firmly es-
tablished. A variety of factors, such as the divergent
toxicity profiles of the agents and the lack of well-de-
fined prognostic patient characteristics, combine to
confound treatment decisions in recurrent NSCLC. Fol-
lowing first-line trials that showed no increased effi-
cacy of concomitant EGFR-TKI and chemotherapy
treatment over chemotherapy alone 16–19, it was pro-
posed that these two types of agents are antagonistic
when given concurrently; specifically, EGFR-TKIs may
interfere with the cell cycle–specific cytotoxicity of
chemotherapy agents 20,21.
These data led to some debate over the effective-
ness of third-line chemotherapy following second-line
EGFR-TKI treatment, but studies have demonstrated that
chemotherapy can indeed be used effectively when pre-
ceded by EGFR-TKIs. For example, the recent
multinational INTEREST trial 22 (n = 1316) demonstrated
TABLE IResults of selected randomized phase III trials in the second-line treatment of non-small-cell lung cancer
Reference Agents Patients Arm Median Response Median 1-Year 2-Year Median
(n) cycles rate survival survival survival survival
(n) (%) (mo.) (%) (%) (mo.)
for PS 0 or 1
in second line
Fossella et al., 2000 5 Docetaxel 373 D100 3 10.8 5.5 21
(TAX320) compared with D75 3 6.7 5.7 32 NA NA
vinorelbine or ifosfamide (V/I)V/I3/2 0.8 5.6 19
Shepherd et al., 2000 6 Docetaxel 104 D100 2 7.1 5.9 19 NA
(TAX317) compared with D75 4 7.1 7.5 37 NA 7.9
best supportive care (BSC)BSC — — 4.6 11 6.3
Hanna et al., 2004 7 Docetaxel 571 D75 4 8.8 7.9 29.7 0 9.1
(JMEI) compared with Pem 4 9.1 8.3 29.7 0 9.4
pemetrexed
Shepherd et al., 2005 8 Erlotinib 731 E150 — a 8.9 6.7 31 13 b 9.4
(BR.21) compared with BSC — — 4.7 21 0 b 6.7
BSC
a Erlotinib was given until disease progression or unacceptable toxicity.
b Personal communication to author.
Adapted from Stinchcombe and Socinski, 2008 9 and Ramalingam and Sandler, 2006 10. PS = performance status; D100 = docetaxel 100 mg/m2 every
3 weeks; D75 = docetaxel 75 mg/m2 every 3 weeks; NA = not available; Pem = pemetrexed 500 mg/m2 every 3 weeks; E150 = erlotinib 150 mg daily.
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CURRENT ONCOLOGY—VOLUME 15, NUMBER 6
that second-line therapy with gefitinib in an unselected
population provided a survival improvement similar to
that of second-line chemotherapy, with a significant
number of patients going on to successfully receive
third-line chemotherapy. In a phase II study of erlotinib
in untreated patients, Giaccone et al. also reported that
most patients went on to receive subsequent treatment
with chemotherapy 23.
Given the similar efficacies of docetaxel, erlotinib,
and pemetrexed, the incurable nature of advanced
NSCLC, and the clinically relevant survival seen in the
second-line setting, clinicians must weigh a variety of
factors when selecting second- and third-line treatment.
The purpose of this retrospective practice review was
to examine the outcomes of second-line erlotinib treat-
ment followed by third-line chemotherapy in the treat-
ment of recurrent metastatic NSCLC in Canadian
clinical practice.
2. METHODS
For this retrospective chart review, we identified pa-
tients with recurrent NSCLC who had received second-
line erlotinib therapy followed by third-line
chemotherapy. Eligible patients were selected by cen-
sus from three major Canadian cancer treatment cen-
tres. All patients had failed prior systemic cytotoxic
therapy and therefore detailed first-line data are not
included in this analysis.
Clinicopathologic demographics collected from
patient medical records were age, ethnicity, sex, NSCLC
pathology (adenocarcinoma, bronchioalveolar, squa-
mous, large-cell, NSCLC not otherwise specified), tu-
mour EGFR status (positive, negative, unknown),
smoking history (current/ever smoker, never smoker),
and PS [Eastern Cooperative Oncology Group (ECOG)
0–3] 24. First-, second-, and third-line treatment data
collected included the type of treatment, reason for
selecting the agent, time to progression (TTP), best re-
sponse [progressive disease (PD), stable disease (SD),
partial response (PR), complete response (CR)], number
of cycles delivered, dose reductions and delays, rea-
son for discontinuation, dose intensity, cancer-related
hospitalizations, and date of death. The presence, on-
set, grade, and resolution of rash during erlotinib treat-
ment were also recorded. Criteria used for classifying
response and progression included the Response Evalu-
ation Criteria in Solid Tumors 25, radiographs, and com-
puted tomography or bone scans.
The study was approved by the ethics committees
and health records departments at all institutions in-
volved. Because the study was an observational, retro-
spective case series, power estimation and analyses
for statistical significance were not performed. Demo-
graphic, treatment, and outcome data are summarized.
3. RESULTS
We identified 35 patients with advanced NSCLC for this
retrospective practice review. Selected study subjects
received second-line erlotinib therapy followed by third-
line chemotherapy in the period between March 2001
and April 2008. Patient data was collected from three
Canadian institutions: the BC Cancer Agency, Vancou-
ver, British Columbia (n = 16); the Jewish General
Hospital, Montreal, Quebec (n = 16); and The Moncton
Hospital, Moncton, New Brunswick (n = 3).
The study population was evenly split between the
sexes and had a median age of 59 years. Most of the
patients were white (66%), but Asian patients accounted
for 31% of the study population. The most commonly
reported pathology was adenocarcinoma (72%), and
most of the patients had an ECOG performance status
of 1 (69%) at the time of metastatic diagnosis. The
proportion of current/ever smokers closely matched the
proportion of never smokers in this population. Table II
presents baseline patient demographics.
3.1 First-Line Therapy
Of the 35 study patients, 97% received standard plati-
num-doublet first-line therapy for advanced NSCLC.
First-line regimens varied by centre; the most com-
mon doublets were cisplatin–gemcitabine (26% of pa-
tients), carboplatin–paclitaxel (23%), and carboplatin–
gemcitabine (20%). The calculated mean first-line TTP
TABLE II Baseline patient (n = 35) characteristics
Characteristic n%
Age (years)
Median 59 —
Range 38–80 —
Sex Male 17 49
Female 18 51
RaceAsian 11 31
White 23 66
Other 1 3
EGFR status by mutation
Positive 3 9
Negative 5 14
Unknown 27 77
Performance status a
0514
12469
2617
Pathology subtype
Adenocarcinoma 25 72
Squamous cell carcinoma 4 11
Bronchioloalveolar carcinoma 1 3
Large-cell 1 3
Non-small-cell lung cancer/ 4 11
not otherwise specified
Smoking status
Current/ever smoker 16 46
Never smoker 19 54
a Eastern Cooperative Oncology Group performance status at
metastatic diagnosis.
EGFR = epidermal growth factor receptor.
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CURRENT ONCOLOGY—VOLUME 15, NUMBER 6
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of 6.6 months and 46% overall response rate (1 CR and
15 PRs) suggest that the study population benefited as
expected from treatment in this setting.
3.2 Second-Line Erlotinib Therapy
All 35 patients received second-line erlotinib treatment
after failing or being unable to tolerate first-line chemo-
therapy. Patients were initiated on the standard dose of
150 mg once daily. In 89% of the patients, no dose
reductions or delays were required throughout second-
line treatment. Patients requiring dose reductions (n =
3) maintained a median dose intensity of 87%. The
average duration of erlotinib treatment was 9.2 months
and the median TTP was 7 months. Based on best re-
sponse in the second line, 40% of patients experienced
a PR, 26% had SD, and 34% had PD. Table III summa-
rizes TTP results for second- and third-line therapy.
3.3 Third-Line Therapy
Of the 35 patients who received second-line erlotinib,
34 went on to receive third-line single-agent chemo-
therapy, and 1 went on to receive the EGFR-TKI gefitinib.
The most common third-line agent was docetaxel (53%),
followed by pemetrexed (24%), gemcitabine (12%), and
vinorelbine (9%). According to records of best response
during third-line therapy, 18% of patients exhibited a PR,
50% maintained SD, and 32% experienced PD. As ex-
pected, the mean third-line TTP of 4.3 months was the
lowest of all lines of therapy. Table III compares key
efficacy parameters for second- and third-line therapy,
including TTP, best response, and PS before therapy.
3.4 Populations of Interest
Further analysis of patient data identified populations
of interest that demonstrated improved TTP with second-
line erlotinib therapy. First, improved outcomes were
observed in the two thirds of patients who developed
rash subsequent to erlotinib treatment. The mean TTP
was 10.5 months for patients with rash as compared
with 5.8 months in patients without rash. Patients who
developed rash were also much more likely to experi-
ence a PR to second-line erlotinib treatment (54%) than
were those without rash (9%). In addition, increasing
TTP was positively associated with increasing grade
of rash severity. Table IV summarizes outcomes in
patients who developed a rash as compared with pa-
tients who did not. These results are consistent with
larger controlled trials of erlotinib for NSCLC that have
demonstrated a positive correlation between rash and
response or survival 16,19,26,27. Figure 1 shows the
Kaplan–Meier estimate of time to progression by grade
of rash. All patients in this practice review that ben-
efited beyond 10 months developed rash secondary to
erlotinib treatment. All rashes were mild-to-moderate
in severity. Treatment varied across centres; however,
all rashes resolved completely.
Never smokers also demonstrated improved out-
comes with second-line erlotinib. The mean TTP of
never smokers was 12.3 months, as compared with
5.6 months for current/ever smokers. Never smokers
were also much more likely to experience a PR to sec-
ond-line erlotinib treatment (63%) than were current/
ever smokers (13%). Table V summarizes patient out-
comes according to smoking history. These results are
consistent with larger controlled trials of erlotinib in
advanced NSCLC. An exploratory multivariate analysis
TABLE III Efficacy results for second- and third-line therapy
Second line Third line
TTP (months) n=33 n=18
Mean 9.2 4.3
Median 7.0 3.5
Range 1.3–28.9 1.2–11.8
n%n%
Best response n=35 n=28
Partial response 14 40 5 18
Stable disease 9 26 14 50
Progressive disease 12 34 9 32
PS before therapy n=35 n=35
0 9 26 7 20
118511028
2 7 20 17 49
31313
TTP = time to progression; PS = performance status.
TABLE IV Effect of rash on outcomes with second-line erlotinib
therapy
Rash No rash
(n=24; 67%) (n=11; 33%)
TTP (months)
Mean 10.5 5.8
Median 8.2 3.3
Range 2.1–28.9 1.3–13.7
n%n%
Best response
Partial response 13 54 1 9
Stable disease 6 25 3 27
Progressive disease 5 21 7 64
Patients Mean TTP Median TTP
(n) (months) (months)
Grade of rash a
1 7 9.1 8.8
2 13 10.4 3.9
3 4 13.5 12.0
a Grade 1 rash = mild; Grade 2 = moderate; Grade 3 = severe/
intolerable.
TTP = time to progression.
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CURRENT ONCOLOGY—VOLUME 15, NUMBER 6
of the BR.21 study revealed that a history of never smok-
ing was predictive both of response to erlotinib and of
survival (HR: 0.8; p = 0.004) 8.
Further analyses of this study population demon-
strated that female sex and Asian race also conferred
improvements in TTP with second-line erlotinib therapy
as compared with male sex and non-Asian race re-
spectively. However, it should be noted that the cur-
rent/ever smoker, male, and non-Asian subgroups also
did better in this review than in previous reports. Our
findings align with analyses from controlled trials, such
as the BR.21 trial, demonstrating that all patient sub-
groups benefit from erlotinib treatment, and that pa-
tients with certain defined clinical characteristics may
do better than the average seen for all second-line
agents 8. We also calculated and compared TTP for
EGFR-positive and EGFR-negative patients; however,
mutational status was unknown for 77% of the study
population. Table VI summarizes TTP with second-line
erlotinib therapy in populations of interest. Figure 2
compares median second-line TTP values for the
populations of interest mentioned here.
4. DISCUSSION
The small size and retrospective nature of this case
series limits the findings of this analysis of second-
line erlotinib in NSCLC patients. In 50% of cases, in-
vestigators cited clinical characteristics associated with
increased response (for example, female sex, Asian
race, positive EGFR mutational status, non-smoking
history) as the reason for prescribing erlotinib in the
second-line setting. This patient selection bias is re-
flected in the overall patient demographics: more than
half the patients enrolled were women, 72% had ad-
enocarcinoma, 31% were Asian, and 54% were never
smokers. This patient selection bias may account for
the high TTP and response rate observed in this analy-
sis. However, the median age of 59 years in this study
is similar to the median age in the pivotal phase III
second- and subsequent-line advanced NSCLC trials
(61, 58, and 62 years respectively) 6,12,15. The propor-
tion of patients with PS 0 or 1 in this study (73%) is also
comparable to the large pivotal trials (76%, 88%, and
66% respectively) 6,7,8.
FIGURE 1 Kaplan–Meier estimate of time to progression by grade of
rash TABLE VI Time to progression (TTP) in populations of interest
with second-line erlotinib therapy
Characteristic Patients TTP (months)
(n) Mean Median
Total population 35 9.2 7.0
Never smokers 19 12.3 10.4
Current/ever smokers 16 5.6 3.9
Women 18 11.1 9.9
Men 17 7.3 4.2
Asian 11 10.2 10.1
Non-Asian 24 8.8 4.9
Rash 24 10.5 8.2
No rash 11 5.8 3.3
EGFR-positive 3 10.8 7.0
EGFR-negative 5 8.7 3.7
Adenocarcinoma histology 25 9.4 7.6
Non-adenocarcinoma histology 10 8.9 3.9
EGFR = epidermal growth factor receptor.
TABLE VSmoking history and second-line erlotinib therapy
Never smokers Current/ever smokers
(n=19, 54%) (n=16, 46%)
TTP (months)
Mean 12.3 5.6
Median 10.4 3.9
Range 2.1–28.9 1.3–14.0
n % n %
Best response
Partial response 12 63 2 13
Stable disease 5 26 4 25
Progressive disease 2 11 10 63
TTP = time to progression.
FIGURE 2 Median second-line time to progression by patient subgroup.
Adeno = adenocarcinoma; EGFR = epidermal growth factor receptor;
pos = positive mutational status; neg = negative mutational status.
SECOND-LINE ERLOTINIB IN NSCLC
CURRENT ONCOLOGY—VOLUME 15, NUMBER 6
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The mean first-line TTP of 6.6 months and response
rate of 46% (15 PR; 1 CR) with platinum-doublet therapy
suggests that the study population benefited as expected
(or better) in this setting as compared with previous
trials. Investigators indicated most often that chemo-
therapy was discontinued because of completion of
therapy (49%), no response or progression (17%), and
because of toxicity such as febrile neutropenia, throm-
bocytopenia, deep vein thrombosis, fatigue, and periph-
eral neuropathology (17%).
In the second-line setting, the study population
demonstrated benefit from second-line erlotinib treat-
ment in advanced NSCLC. The median overall TTP of
7.0 months and the response rate of 40% with sec-
ond-line erlotinib treatment in this study were greater
than those reported in the pivotal phase III studies ex-
amining outcomes in the second-line treatment of
advanced NSCLC 6,7,8. In our analysis, dose intensity
was well maintained throughout second-line treatment,
with only 3 patients requiring dose reductions. Erlotinib
was well tolerated, with an average duration of treat-
ment of 9.2 months. Investigators cited progression
as the rationale for 88% of cases in which erlotinib
was discontinued. Side effects, including gastroin-
testinal symptoms, were the reason for 12% of erlotinib
discontinuations. In 5 patients, hospitalization occurred
for cancer-related reasons. Clinicians noted symptom
improvement in 23% of patients during second-line
erlotinib treatment. In 13% of patients, PS improved;
it remained stable in 50%; and it worsened in 37% of
patients.
Third-line chemotherapy in this case series involved
many different agents, including docetaxel (most com-
monly used), pemetrexed, gemcitabine, and
vinorelbine. Third-line therapy following erlotinib was
observed to be effective in this analysis, with a me-
dian TTP of 3.5 months and an overall response rate of
18%. These results compare closely to third-line re-
sults observed by Ng et al. in a similar Canadian retro-
spective review 28 (n = 21): for docetaxel, median TTP
was 4.2 months with a 5% response rate.
Median time to death after discontinuation of third-
line chemotherapy in the present case series was 5.4
months. Four patients are still receiving third-line
chemotherapy, and 2 patients are currently receiving
fourth-line therapy with docetaxel.
Our data demonstrate that metastatic NSCLC pa-
tients who are able to receive third-line chemotherapy
following second-line erlotinib both tolerate it and ben-
efit from it. In the present study, we observed greater
response rates and TTP from second-line therapy than
has previously been reported in controlled trials. That
result may be somewhat an effect of the partially se-
lected population. Another possible explanation for the
extended benefit may be clinicians’ improved ability
to manage patients who develop a skin rash, and thus
avoid dose reductions or discontinuations, especially
in light of continuing evidence that rash is an indicator
of additional benefit to the patient 29,30.
The results of our case series further support the
evidence that it is appropriate to consider 3 lines of
treatment in patients with advanced NSCLC. In addi-
tion, erlotinib benefits patients in all demographics, and
second-line EGFR-TKI followed by chemotherapy is an
effective treatment option.
5. CONCLUSIONS
For patients with advanced NSCLC who progress fol-
lowing first-line platinum-based chemotherapy, our
retrospective practice review demonstrates that sec-
ond-line EGFR-TKI treatment with erlotinib is effica-
cious and well tolerated. In addition, second-line
erlotinib treatment does not appear to diminish ben-
efit from subsequent third-line chemotherapy. And al-
though certain patient subgroups exhibited improved
TTP during second-line therapy, patients without the
clinical characteristics associated with increased re-
sponse to EGFR-TKIs also demonstrated benefit from
erlotinib treatment.
Three lines of therapy should be considered for
patients with metastatic NSCLC. Choice of second-line
and subsequent therapy should be individualized based
on numerous considerations such as symptom improve-
ment, PS, patient comorbidities, toxicity, QOL consid-
erations, patient preference, convenience, and ease of
administration.
6. ACKNOWLEDGMENTS
The authors acknowledge the support of Hoffmann–La
Roche Ltd. (Canada) through an unrestricted educational
grant. The authors also acknowledge the medical writ-
ing contributions of Ms. Andrea Burdett of Klick Com-
munications Inc. and the data collection efforts of Ms.
Tracey Allen of The Moncton Hospital and Dr. Goulnar
Kasymjanova of the Jewish General Hospital.
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Correspondence to: Barbara Melosky, BC Cancer
Agency, 600 West 10th Avenue, Vancouver, British
Columbia V5Z 4E6.
E-mail: BMelosky@bccancer.bc.ca
* BC Cancer Agency, Vancouver, BC.
†Jewish General Hospital, Montreal, QC.
‡The Moncton Hospital, Moncton, NB.
