TOKYO, JapanLarge, multicenter trials underway in the
United Kingdom are questioning whether chemotherapy is actually worth it for
patients with advanced non-small-cell lung cancer (NSCLC), according to Jeremy
Steele, MD, of the Division of Hematology, Oncology and Imaging, St.
Bartholomew’s Hospital, London.
Some studies are looking at the role of platinum-based and
newer agents, while others are exploring the role of hyper-fractionated
radiotherapy in stage IIIA/B disease.
"In the UK, many respiratory physicians and patients
remain uncertain about the value of chemotherapy in NSCLC," Dr. Steele
said at the 9th World Conference on Lung Cancer. Respiratory physicians, who
care for most lung cancer patients in the United Kingdom, use chemotherapy in
just a small proportion of patients with advanced disease.
The Big Lung Trial
The Big Lung Trial (BLT) is looking at the effect of cisplatin
(Platinol)-based regimens in NSCLC at any stage, including advanced disease.
The trial design stems in part from a previous meta-analysis of
52 randomized clinical trials, including more than 9,000 patients. The results
showed that cisplatin-based chemotherapy provided a modest survival advantage,
particularly when combined with best supportive care or radical radiotherapy
(NSCLC Collaborative Group: Br Med J 311:899-909, 1995).
Conducted at 72 UK and 8 international centers, the BLT study
specifically includes patients in whom the value of chemotherapy is thought to
be marginal. The patients are randomized to one of four chemotherapy regimens
or no chemotherapy. All patients in the study receive best supportive care.
The four active treatment regimens, given in three cycles at
21-day intervals, include: vindesine (Eldesine)/cisplatin; vinorelbine
(Navelbine)/cisplatin; mitomycin (Mutamycin)/ifosfamide (Ifex)/cisplatin (the
MIC regimen); and mitomycin/vinblastine/cisplatin (the MVP regimen).
The study will look not only at endpoints of survival and
progression but also at questions of quality of life and health economics.
At the time of the World Conference on Lung Cancer meeting,
patient accrual in the best supportive care arm had reached 650 patients, with
a target of 800 patients. Recruitment is expected to be completed by the autumn
Other Ongoing Trials
Dr. Steele described three other ongoing UK trials of
chemotherapy in NSCLC. The London Lung Cancer Group is evaluating gemcitabine
(Gemzar) plus carboplatin (Paraplatin) vs the MIC regimen in patients with
histologically or cytologically proven stage IIIB/IV disease.
In this randomized, phase III trial to include 387 patients,
either therapy is given in four courses at 21-day intervals. Besides common
response and toxicity endpoints, quality of life is of special concern.
Patients will complete a European Organization for Cancer Research and
Treatment (EORTC) quality-of-life questionnaire plus a lung cancer module.
Accrual is ongoing.
The CHARTWEL study (Continuous Hyperfractionated Accelerated
Radiotherapy With Weekend Leave), in progress, is a phase II evaluation of
hyperfractionated radiotherapy following chemotherapy.
Conducted at Mount Vernon Hospital, London, the study is
predicated on an earlier trial showing that, for patients with localized,
inoperable NSCLC, hyperfractionated radiotherapy provides a survival advantage
over conventional radiotherapy (Saunders M et al: Lancet 350:161-165, 1997).
"There exists the exciting possibility that the addition
of chemotherapy to hyperfractionated radiotherapy could lead to a further
improvement in survival," Dr. Steele said. So far, however, only limited
data exist on the tolerability and efficacy of the particular combination being
used in the study: three cycles of paclitaxel (Taxol)/carboplatin followed by
Another study to watch asks whether synthetic erythropoietin
(epoetin alfa, Epogen, Procrit) will affect survival and quality of life in
stage IIIB/IV disease with respect to anemia. The randomized phase III study
will require 448 patients, all undergoing cisplatin-based therapy with or
without epoetin alfa, to demonstrate a difference in anemia-related quality of
life, hemoglobin response, and survival.
Epoetin alfa is administered at 10,000 IU subcutaneously three
times a week, starting at onset of anemia and continuing to approximately 1
month after therapy ends.
"This study, now in progress, should help determine the
role of this novel agent in reducing the toxicity of chemotherapy," Dr.