Lung cancer research at UCL/UCLH sets standards of care
Submitting InstitutionUniversity College London
Unit of AssessmentClinical Medicine
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Oncology and Carcinogenesis
Summary of the impact
UCL has conducted a series of national lung cancer trials, which have led
to wide-scale changes in clinical practice. Two trials compared different
platinum based therapies, which led to centres switching from using
chemotherapy with cisplatin to carboplatin-based chemotherapy instead.
Carboplatin can be given as an outpatient, and has fewer side effects, and
has been (and still is) recommended as an alternative to cisplatin in the
UK and US.
Lung cancer is the most common cause of cancer death in the UK and other
developed countries. The CR-UK & UCL Cancer Trials Centre (CTC), with
the London Lung Cancer Group (LLCG), has an established history (almost 30
years) of conducting large scale national trials in lung cancer treatment
and screening. The chair of the LLCG is Professor Siow Ming Lee, based at
Gemcitabine/carboplatin as first-line treatment for lung cancer (known
as studies 10 and 11)
These were two national clinical multicentre trials in lung cancer,
initiated, developed and conducted through UCL, to examine the efficacy
and safety of gemcitabine/carboplatin (gem/carbo) in two different types
of lung cancer. The Chief Investigator was Professor Siow Ming Lee. Both
trials were independently peer-reviewed by Cancer Research UK and were
conducted through the UK National Cancer Research Networks. All of the
trials were large collaborative multicentre studies involving as many as
95 hospitals across the UK.
Study 10 (extensive or limited stage small cell lung cancer
(SCLC) with poor prognosis): compared gem/carbo with standard
cisplatin/etoposide (PE) in 241 patients. This was the first randomised
study comparing these two chemotherapy regimens for patients with
poor-prognosis small cell lung cancer (SCLC). It showed that gem/carbo had
similar survival outcomes to PE, but was better tolerated. Patients given
gem/carbo received more chemotherapy as outpatients (89% vs. 66%), and
fewer had nausea and alopecia (the two most commonly reported side effects
associated with lower quality of life) .
Study 11 (stage IIIb or IV non-small cell lung cancer
(NSCLC)): gem/carbo was compared with standard mitomycin, ifosfamide, and
cisplatin (MIC), This trial, based on 422 patients, showed for the first
time that outpatient chemotherapy was more effective than conventional
inpatient chemotherapy, improving median survival from 7.6 to 10.0 months
(24% reduction in mortality) and one-year survival from 30% to 40%.
Furthermore, quality of life was significantly improved, because patients
given gem/carbo had fewer side effects . An added advantage was
that gem/carbo avoided the inconvenience and NHS cost of an overnight stay
References to the research
(Those in bold are UCL-based; James and Gower were in the clinical trials
 Study 10. Lee SM, James LE, Qian W, Spiro S, Eisen T,
Gower NH, Ferry DR, Gilligan D, Harper PG, Prendiville J, Hocking
M, Rudd RM. Comparison of gemcitabine and carboplatin versus cisplatin and
etoposide for patients with poor-prognosis small cell lung cancer. Thorax.
 Study 11. Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG,
Littler JA, Hatton M, Johnson PW, Martin WM, Rankin EM, James LE,
Gregory WM, Qian W, Lee SM. Gemcitabine plus carboplatin versus
mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV
non-small-cell lung cancer: a phase III randomized study of the London
Lung Cancer Group. J Clin Oncol. 2005 Jan;23(1):142-53. http://dx.doi.org/10.1200/JCO.2005.03.037
Funding for both trials: Eli Lilly
Details of the impact
The combination of mitomycin, ifosfamide, and cisplatin (MIC) was
previously widely used in Europe for the treatment of advanced NSCLC. This
required patients to stay in hospital overnight, and had adverse effects
on quality of life. Cisplatin and etoposide (PE) were commonly used
together to treat poor prognosis SCLC. However, major problems with
cisplatin treatment were the administration time and significant
symptomatic non-haematological toxicity.
Gemcitabine/carboplatin (gem/carbo) became popular because it was given
as an out-patient treatment with short infusion time. It was also better
tolerated, causing less emesis, renal impairment, hearing loss and
neurotoxicity compared to other regimens. In addition, many NSCLC patients
are elderly (median age 72) with poor performance status and have multiple
co- morbidities, so clinicians often recommend carboplatin instead of
cisplatin to treat this population group. Gem/carbo therefore became
widely used as a first-line treatment in the UK and internationally to
treat patients with advanced NSCLC (Lilly data). In 2009, NICE guidance
recommended pemetrexed-based chemotherapy for NSCLC [a], and since
that time, gem/carbo has been used mainly to treat SCLC (NICE guidelines
TA26 [b] and CG121 [c]).
The following recommendations are from the NICE website (accessed 30
April 2013), based on the findings of the UCL trials:
"Early stage (broadly T1-2a, N0, M0) or limited disease (broadly T1-4,
Consider carboplatin if renal function impaired, poor performance
status (WHO 2 or more) or significant comorbidity"
Extensive disease (broadly T1-4, N0-3, M1a/b)
Offer platinum-based combination chemotherapy (maximum 6 cycles) if
patient can receive chemotherapy".
"For advanced NSCLC, offer a combination of a single third-generation
drug (docetaxel, gemcitabine, paclitaxel or vinorelbine) plus a platinum
drug (either carboplatin or cisplatin)."
As a result of the national guidance, gem/carbo was used as a reference
regimen in the BTOG 2 trial (a large national clinical trial of 1,350
NSCLC patients) to compare low dose and high dose platinum regimens [f].
The study shows gem/carbo was well tolerated and superior to low dose
cisplatin but has similar outcome compared to high dose cisplatin regimen
The Study 10 findings are also quoted in the US National Comprehensive
Cancer Network (NCCN) guidelines to support the use of carboplatin to
treat extensive SCLC [h]. Individual patient data from Study 10
were used for the meta-analysis comparing the efficacy of cisplatin versus
carboplatin in the first-line treatment of SCLC [i]. There is also
reference to Study 10 in Canadian guidelines on bladder cancer [j].
Approximately 4,000 new cases of SCLC are diagnosed in the UK each year.
The majority of these patients have extensive SCLC and poor performance
status and hence many are treated with a carboplatin-based regimen instead
of a cisplatin-based treatment. A carboplatin regimen can be easily
administered as an out-patient regimen reducing chair time usage and
avoiding the inconvenience of prolonged hydration or overnight stay
associated with cisplatin and also fewer of the adverse effects that are
commonly seen with cisplatin administration.
The Systemic Anti-Cancer Therapy (SACT) Dataset, within the National
Cancer Intelligence Network, has been recording data on types of
treatments for lung cancer since April 2012. For 2012 there were 3,686
SCLC cases recorded in England and Wales. The SACT dataset shows that
between April 2012 and March 2013, 710 patients with SCLC received
carboplatin, though only around 80% of trusts had uploaded data so the
actual number is likely to be nearer 900, meaning that 26% of SCLC
patients received carboplatin [k].
Sources to corroborate the impact
[a] NICE: The diagnosis and treatment of lung cancer. April 2011. NICE
Clinical Guideline 121. http://www.nice.org.uk/nicemedia/live/13465/54202/54202.pdf
[b] NICE Guideline TA26. http://guidance.nice.org.uk/TA26
[c] NICE Guideline CG 121. http://www.nice.org.uk/CG121
[d] Full guideline references our studies.
[e] Full guideline references our studies.
[f] BTOG 2 trial. http://clinicaltrials.gov/ct2/show/NCT00112710
[g] Ferry et al. British Thoracic Oncology Group Trial, BTOG2: Randomised
phase III clinical trial of gemcitabine combined with cisplatin 50mg/m2
(GC50) versus cisplatin 80mg/m2 (GC80) versus carboplatin AUC 6 (GCb6) in
advanced NSCLC. Presented at the World Conference on Lung Cancer 2011. http://abstracts.webges.com/wclc2011/myitinerary
[put `BTOG2' in the search field, and the Ferry et al abstract will be
[h] US NCCN Guideline: Kalemkerian GP, Akerley W, Bogner P, Borghaei H,
Chow LQ, Downey RJ, Gandhi L, Ganti AK, Govindan R, Grecula JC, Hayman J,
Heist RS, Horn L, Jahan T, Koczywas M, Loo BW Jr, Merritt RE, Moran CA,
Niell HB, O'Malley J, Patel JD, Ready N, Rudin CM, Williams CC Jr, Gregory
K, Hughes M. Small cell lung cancer. J National Comprehensive Cancer
Network. 2013;11(1):78-98. Available on request.
[i] Rossi A, Di Maio M, Chiodini P, Rudd R, Okamoto H, Skarlos DV, Früh
M, Qian W, Tamura T, Samantas E, Shibata T, Perrone F, Gallo C, Gridelli
C, Martelli O, Lee SM (2012). Carboplatin-or cisplatin-based chemotherapy
in first-line treatment of small-cell lung cancer. The COCIS meta-analysis
of individual patient data. Journal of Clinical Oncology 2012;
[j] Moretto et al. Management of small cell carcinoma of the bladder:
Consensus guidelines from the Canadian Association of Genitourinary
Medical Oncologists (GAGMO). Can Urol Assoc J 2013;7:E44-E56. http://dx.doi.org/10.5489/cuaj.220
[k] Data and estimated data provided by Clinical Lead, National Cancer
Intelligence Network (NCIN). Copy available on request.