In spite of a worldwide intensification of the battle against tobacco
consumption, the incidence of lung cancer continuesto rise in
parallel with the increased consumption of tobacco.This is
especially so in women in Western countries and in menand women in
developingcountries.
Major strides have been made in our knowledge of the biology of lung cancer.
But we still await the impact of this informationon prevention,
early diagnosis, and cure rate, which has beenessentially unchanged
during the past couple of decades, witha five year survival rate for
non-small cell lung cancer of 8-14%.The figures vary somewhat from
country to country, with almosthalf the patients dying within the
first year of diagnosis inspite of the best clinical treatments.1
Non-small cell lung cancer includes squamous cell carcinoma, adenocarcinoma,
and large cell carcinoma. It accounts for 75-80%of all new patients;
the remaining are small cell carcinomas.Of all patients with newly
diagnosed non-small cell lung cancer,70-75% have locoregional or
advanced, unresectable disease. Recentlarge studies and
meta-analyses have clearly shown the benefitof combined modality
treatment (chemotherapy with or without surgerywith or without
radiotherapy) with improvements in median andtwo year survival for
patients with locoregional disease, whilethe treatment of advanced
disease is still being debated. 23
Until the late 1990s, the most commonly accepted symptomatic treatment
consisted of palliative radiotherapy. A recent Cochranereview of 10 randomised
trials using varying doses of radiotherapyconcluded that there is no
strong evidence that any regimen givessuperior palliation.4
A recent British study with 148 patientschallenges this conclusion
by showing that fractionated thoracicirradiation (30 Gy in 10 daily
fractions) afforded better reliefof symptoms and reduced anxiety
compared with single fractions(10 Gy), but did not increase
survival.5 According to the Cochrane
review, there is evidence for a modest increase in survival (6%at
one year and 3% at two years) in patients with good performance
status given higher doses ofradiotherapy.
With palliation as the aim, most patients should be treated with short
courses of one or two fractionsas
in the study inthis issue by the Medical Research Council's lung
cancer workingpartyusing
either 17 Gy as two 8.5 Gy fractions one week apartor less
frequently 10 Gy as a single dose, based on two previousMRC trials
(p
465).6 Patients were randomised with a
reasonablestratification to supportive treatment plus either
immediate ordelayed thoracic radiotherapy. The study included
230 patientswith non-small cell lung cancer that was locally too
advancedfor surgical resection or intensive radiotherapy with
curativeintent. Cytostatic chemotherapy was not permissible in any
group.The median time to start of thoracic radiotherapy was 15 daysin the intermediate group and 125 days in the delayed group. No
differences were noted in primary study measures such as percentage
of patients alive and without moderate or several local symptoms,nor
were there any differences in secondary measures, such asquality of
life, adverse events, or survival. Interestingly, 58%of the patients
in the delayed group did not receive thoracicradiotherapy at all,
thus reserving the much needed capacity ofoncology centres for other
patients in need ofirradiation.
This study took place over a six year period in the mid-1990s. In the
meantime evidence has emerged, based on meta-analysisincluding
Cochrane analyses, that combination chemotherapy withcisplatin in a
similar group of patients results in improvementin one year survival
by 10% provided that the patients had a goodperformance status at
the time of diagnosis. 78
Symptomaticimprovement is reported in 60% of all such patients.
Further,patients with progressive disease during chemotherapy have
beenshown in two recent randomised studies to benefit from singleagent chemotherapy, based on both survival and control of symptoms.
910
The picture has thus changed since the conclusion of the trial reported in
this issue leaving a number of questions open forfuture studies.
These include a clarification of whether or notdelayed chemotherapy
is as effective as immediate chemotherapyfor certain selected groups
of patients, as shown for radiotherapyin this study,6
or whether the two modalities should be combinedand administered at
the time ofdiagnosis.
Considering the large number of patients and the implications for resources
available in the healthcare system, carefullyplanned multinational
studies are needed, including socioeconomicanalyses, as well as
prospective trials including patients withpoor performance status.11
Until results from such studies becomeavailable, the management of
patients with advanced non-smallcell lung cancer should be discussed
carefully with patients andrelatives, and detailed information
should be given regardingthe benefits and harms associated with the
treatment and the timingofit.
Heine H Hansen.
Finsen Center, 5072, National University Hospital, DK-2100 Copenhagen,
Denmark (hansenhh@iaslc.org)
Marino P, Preatoni A, Cantoni A. Randomized trials of
radiotherapy alone versus combined chemotherapy and radiotherapy in stages
IIIa and IIIb non-small cell lung cancer: a meta-analysis. Cancer
1995; 76: 593-601[Medline].
Pritchard RS, Anthony SP. Chemotherapy plus radiotherapy
compared with radiotherapy alone in the treatment of locally advanced,
unresectable non-small-cell lung cancer: a meta-analysis. Ann Intern Med
1996; 125: 723-729[Medline]
(Erratum, Ann Intern Med 1997;126:670).
Macbeth F, Toy E, Coles B, Melville A, Eastwood
A. Palliative radiotherapy regimens for non-small cell lung cancer.
Cochrane Database Syst Rev 2002;1:CD002143.
Falk SJ, White RJ, Hopwood P, Girling DJ, Harvey A, Qian W,
et al. Immediate versus delayed palliative thoracic radiotherapy in patients
with unresectable locally advanced non-small cell lung cancer and minimal
thoracic symptoms: results of a randomised controlled trial. BMJ
2002; 325: 465-468[Abstract/Full
Text].
Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R,
O'Rourke M, et al. Prospective randomized trial of docetaxel versus best
supportive care in patients with non-small cell lung cancer previously
treated with platinum-based chemotherapy. J Clin Oncol 2000; 18:
2095-2103[Abstract/Full
Text].
Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR,
Dunphy F, et al. Randomized phase III trial of docetaxel versus vinorelbine
or ifosfamide in patients with advanced non-small cell lung cancer
previously treated with platinum-containing chemotherapy regimens. J Clin
Oncol 2000; 18: 2354-2362[Abstract/Full
Text].
PAPERS Immediate versus delayed palliative thoracic radiotherapy in patients
with unresectable locally advanced non-small cell lung cancer and minimal
thoracic symptoms: randomised controlled trial.
Stephen J Falk, David J Girling, Roger J White, Penelope Hopwood, Angela
Harvey, Wendi Qian, and Richard J Stephens
BMJ 2002 325: 465. [Abstract][Abridged text][Full text]
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