MAYWOOD, IllRemoving the cancerous kidney before administering
interferon alfa-2b (Intron A) improves survival in advanced renal
cancer, according to results of Southwest Oncology Group (SWOG) Trial
8949. The role of interferon treatment, however, remains
In a plenary presentation at the ASCO Annual Meeting, Robert Charles
Flanigan, MD, of Loyola University Stritch School of Medicine,
Maywood, Illinois, said that overall survival and 1-year survival in
the SWOG trial were both significantly longer in patients who
received nephrectomy before interferon than in those treated with
Acting as discussant for this paper, Ian Tannock, MD, PhD, of
Princess Margaret Hospital, Toronto, agreed that the increase in
overall survival from 8.1 to 11.1 months was statistically
significant. He added, however, that interferon should not be
considered standard therapy in metastatic renal cancer.
"Although there are two trials showing survival benefit from use
of high-dose interferon for metastatic disease, the treatment has a
major negative impact on quality of life, and there are three large,
unpublished trials that have found no benefit to interferon when used
as an adjuvant to surgery for locally advanced renal cancer,"
Dr. Tannock stated.
Impetus for SWOG Trial
The SWOG trial was undertaken, according to Dr. Flanigan, because a
potential benefit of nephrectomy in metastatic renal cancer patients
had been reported from case series data. A SWOG review of cases found
median survival of 11.4 months with nephrectomy followed by biologic
response modifier treatment vs 5.9 months without prior nephrectomy.
SWOG 8949 randomized 121 patients to interferon alfa-2b treatment
with no nephrectomy and 120 to interferon alfa-2b preceded by radical
nephrectomy. Type of nephrectomy was not controlled, but surgery had
to occur within 4 weeks of study entry.
Interferon was given weekly at 5 million IU/m² on Monday,
Wednesday, and Friday until disease progression occurred.
The primary study endpoint was survival, and the secondary endpoint
was clinical response. The trial was designed with an 85% power to
detect a 50% difference in survival and a 15% difference in clinical
Varying Survival Rates
Dr. Flanigan reported that median overall survival was 8.1 months
with interferon alone vs 12.5 months with nephrectomy plus interferon (P
= .006). In patients with performance status (PS) 0, median overall
survival was 12.8 months with interferon vs 17.4 months with surgery
plus interferon. In PS 1 patients, overall survival was 4.8 months
with interferon vs 11.1 months with surgery plus interferon.
Dr. Tannock pointed out that there was a chance imbalance in the
distribution of patients between the two arms, with better
performance status patients assigned to the surgery arm. This could
explain some of the apparent benefits of surgery. However, there was
still a difference when the subgroups of patients with PS 0 and PS 1
were compared between the two arms.
In patients with measurable disease, overall survival was 11.2 months
with interferon vs 16.4 months with surgery plus interferon. In
patients with evaluable but unmeasurable disease, overall survival
was 7.7 months with interferon vs 10.3 months with surgery plus
interferon (P = .0005).
One-year actuarial survival was also significantly better in patients
who received surgery before interferon than in those receiving
interferon alone .
Dr. Flanigan said that response rates were low in this trial: 3% in
the nephrectomy/interferon arm (3 partial responses) and 4% in the
interferon-only arm (1 complete response, 2 partial responses).
Eighty percent of patients had no complications associated with
surgery, and there was only one surgical death. One patient (0.5%)
died of interferon-related cardiovascular toxicity. Grade 4
toxicities affected 10 of 121 patients (8.3%) in the nonnephrectomy
arm and 13 of 120 patients (10.8%) in the nephrectomy arm.
New Standard of Care?
The survival advantage was only 4 to 5 months, but it does
represent a 50% increase with treatment that would not now be
considered standard therapy, Dr. Flanigan said. This is
the first randomized, prospective trial of cytoreduction nephrectomy
in advanced renal cancer. It shows that this should probably be the
new standard of care, but only select patients, such as those with
good performance status, may benefit substantially.
Dr. Tannock said that the SWOG results showing that nephrectomy
before interferon improved survival in all of the stratified patient
groups were confirmed by a smaller studyEuropean Organization
for Research and Treatment of Cancer (EORTC) 30947presented at
the American Urological Association meeting.
This study, with 83 patients randomized, was small but
confirmatory, Dr. Tannock said. There was a significant
survival advantage in favor of nephrectomy.
Where Controversy Lies
Surgery can be recommended to patients with higher performance
status, Dr. Tannock added, but noted that the results of the
SWOG and EORTC studies should not be generalized to patients with
lower performance status.
Dr. Tannock challenged the use of interferon as standard treatment in
advanced renal cancer. Although a Medical Research Council study
showed a survival advantage from use of interferon, it also showed
high rates of side effects (particularly depression) and decreased
quality of life.
Three trials have shown no benefit to adjuvant therapy with
interferon. One suggested there is a benefit. Although the negative
studies were large trials, none have been published, apparently due
to publication bias, Dr. Tannock said. The small gains in
survival come at the cost of a significant decrement in quality of life.