Studies
presented at the ASCO Annual Meeting in the field of noncolorectal
gastrointestinal cancer both reaffirmed certain standards of care
and introduced some practice-changing data, according to A.
Craig Lockhart, MD, of Washington University in St.
Louis.
Perioperative
Therapy for Gastric Cancer
After curative resection
of gastric or gastroesophageal junction cancer, the combination of
ECF (epirubicin, cisplatin, and infusional 5-FU) is not more
efficacious or safer than the standard of bolus fluorouracil (5-FU)
and leucovorin when incorporated into a chemoradiation scheme,
according to findings of the Cancer and Leukemia Group B (CALGB)
80101 trial.1
Among 546 patients with
resected tumors, each regimen was given before and after
chemoradiation. The postchemoradiation doses of epirubicin and
cisplatin in ECF were reduced because of toxicity concerns. Trial
results showed that the two groups did not differ significantly
regarding disease-free and overall survival, and had similar rates
of toxicities.
"A question that came up
is, did the downgrading of the epirubicin and cisplatin doses
potentially impact the efficacy [of the ECF]. I don't think we have
the answer at this time," Dr. Lockhart said.
"It does not appear that
ECF is any better than the standard Intergroup 0116 approach" of
5-FU/leucovorin, he commented. "Incorporating ECF, making the 0116
regimen more complicated by adding other drugs to it, does not
appear to improve survival, so the 0116 approach is still a
standard."
Adjuvant
XELOX in Gastric Cancer
The phase III
CLASSIC trial showed that giving XELOX (capecitabine [Xeloda] plus
oxaliplatin) in the adjuvant setting improves disease-free survival
in gastric cancer even after the more extensive D2
resection.2
In all, 1,035 patients in
South Korea, China, and Taiwan underwent a D2 resection and were
randomly assigned to XELOX or observation. Median dose intensity
was 85% for capecitabine and 98% for oxaliplatin, and there were no
unexpected toxicities.
The 3-year rate of
disease-free survival was better with XELOX (74% vs 60%; HR =
0.56;P < .0001; Fig. 1). Rates of recurrence were
reduced at all sites: locoregional, peritoneal, and distant.
Overall survival did not differ. "But this study had not been going
on long enough to look at that definitively," Dr. Lockhart
noted.
"Adjuvant XELOX is a
standard option following a D2 resection," he concluded. "In my
opinion, this is practice-changing."
Second-line
Chemotherapy for Advanced Gastric Cancer
Second-line chemotherapy
has a 1.3-month survival benefit in fit patients with advanced
gastric cancer, a phase III trial revealed.3
The 193 patients were
randomly assigned 2:1 to second-line chemotherapy (docetaxel or
irinotecan) or best supportive care. Relative dose intensity was
95% for docetaxel and 93% for irinotecan.
With a median follow-up
of 17 months, overall survival was better with second-line
chemotherapy than with best supportive care (5.1 vs 3.8
months,P = .009). Benefit did not differ between docetaxel
and irinotecan recipients.
"Interestingly, no
quality-of-life data were presented," Dr. Lockhart noted. However,
there was a trend toward a lower rate of grade 3/4 fatigue with
chemotherapy vs best supportive care (18% vs 27%). And a similar
study of second-line irinotecan found an improvement in
symptoms.4
"Second-line chemotherapy
can be considered a standard approach for patients with good
performance status…who want to receive second-line therapy," he
maintained.
Sorafenib for
Child-Pugh B Patients with Hepatocellular Carcinoma
Patients with advanced
hepatocellular carcinoma having Child-Pugh B class liver function
may derive some benefit from sorafenib (Nexavar) and can start on
the full dose, according to new data.5
In a second interim
analysis of the GIDEON study, which is assessing sorafenib therapy
in routine clinical practice, investigators analyzed data from
1,612 patients. The Child-Pugh class was A, B, and C in 70%, 27%,
and 3% of patients, respectively.
The majority of patients
received the full 800-mg dose of sorafenib, regardless of
Child-Pugh class. However, the median treatment duration fell off
with class-it was 14, 9, and 4 weeks with A, B, and C class. The
corresponding rate of adverse events leading to treatment
discontinuation was 24%, 38%, and 51%.
Median overall survival
was 10.3, 4.8, and 2.0 months. The 10.3 months in patients with
class A liver function is "reassuring" because it mirrors that in
clinical trials, according to Dr. Lockhart. The results suggest the
same dosing strategy can be used for patients with Child-Pugh A and
B class, he said.
"Right now, there is no
indication to treat Child-Pugh C patients with sorafenib," Dr.
Lockhart maintained. "I would argue that Child-Pugh B patients
probably don't benefit much from sorafenib either, but if you don't
have other options, such as a clinical trial, I don't think it's
wrong to [offer it]."
Cisplatin in
Chemoradiation for Anal Cancer
Cisplatin is not superior
to the standard mitomycin when used with 5-FU in chemoradiation for
rectal cancer, according to long-term results of the Radiation
Therapy Oncology Group (RTOG) 98-11 trial.6
A total of 650 patients
were randomly assigned to cisplatin (induction with 5-FU and
cisplatin before chemoradiation with 5-FU and cisplatin) or
mitomycin (only chemoradiation with 5-FU and mitomycin). Compared
with cisplatin, mitomycin yielded higher 5-year rates of
disease-free survival (67.7% vs 57.6%,P = .004) and
overall survival (78.2% vs 70.5%,P = .02), and a trend
toward a lower rate of colostomy failure (11.9% vs 17.3%,P
= .075). Male sex, a primary tumor larger than 5 cm, and clinically
positive lymph nodes were all independent adverse prognostic
factors.
"The results remain
somewhat surprising as we thought cisplatin was going to
potentially change the way that we practice. It did not," Dr.
Lockhart asserted. "5-FU/mitomycin along with radiation therapy
remains the standard for patients with anal canal carcinomas."
■
Disclosure: Dr. Lockhart has received
research funding from Allos, Amgen, Bayer, Imclone/Lilly, Novartis,
Merck, Millennium, Pfizer, Sanofi-Aventis, and Zenyaku.
SIDEBAR:
Will East-West Differences Limit Transferability of Clinical Trial
Results?
References
1. Fuchs CS, Tepper JE,
Niedzwiecki D, et al: Intergroup trial CALGB 80101. 2011 ASCO
Annual Meeting.
Abstract 4003. Presented June 7, 2011.
2. Bang Y, Kim YW, Yang
H, et al: Adjuvant capecitabine and oxaliplatin for gastric cancer:
Results of the phase III CLASSIC trial. 2011 ASCO Annual Meeting.
Abstract LBA4002. Presented June 7, 2011.
3. Park SH, Lim DH,
Park K, et al: A multicenter, randomized phase III trial comparing
second-line chemotherapy plus best supportive care with BSC alone
for pretreated advanced gastric cancer. 2011 ASCO Annual Meeting.
Abstract 4004. Presented June 7, 2011.
4. Thuss-Patience PC,
Kretzschmar A, Bichev D, et al: Survival advantage for irinotecan
versus best supportive care as second-line chemotherapy in gastric
cancer: A randomised phase III study of the AIO.
Eur J Cancer July 8, 2011 (early release online).
5. Marrero JA, Lencioni
R, Kudo M, et al: Global Investigation of Therapeutic Decisions in
Hepatocellular Carcinoma and of its Treatment with Sorafenib
(GIDEON) second interim analysis in more than 1,500 patients. 2011
ASCO Annual Meeting.
Abstract 4001. Presented June 7, 2011.
6. Gunderson LL, Winter KA, Ajani JA, et al: Long-term update of
U.S. GI intergroup RTOG 98-11 phase III trial for anal carcinoma.
2011 ASCO Annual Meeting.
Abstract 4005. Presented June 7, 2011.
