Improving Survival Without Reducing Quality of Life in Small-Cell Lung Cancer Patients by Increasing the Dose-Intensity of Chemotherapy With Granulocyte Colony-Stimulating Factor Support: Results of a British Medical Research Council Multicenter Randomized Trial

Thatcher, Nicholas; Girling, D J; Hopwood, Penelope; Sambrook, Robert; Qian, Wendi; Stephens, Richard

doi:10.1200/jco.2000.18.2.395

Cited by 209 publications

(93 citation statements)

References 19 publications

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“…The rate or TRT was lower for patients receiving ACE (58%) than those receiving PE (74%). The reason for this is unclear, but is likely to reflect the worse toxicity seen with ACE, and is similar to the 51 -54% reported in comparable studies (Thatcher et al, 2000;Ardizzoni et al, 2002). Higher TRT rates have also been reported for other platinum combinations (Lorigan et al, 2005;Thatcher et al, 2005).…”

Section: Discussionsupporting

confidence: 61%

“…S Baka et al lower than that reported for two studies from the UK Medical Research Council, but these studies had fewer ED patients (Thatcher et al, 2000;Thatcher et al, 2005). The median and 2-year survivals for PE in LD patients in our study were lower than those reported by Sundstrom (12.6 vs 14.5 months,21 vs 25%,respectively).…”

Section: Discussioncontrasting

confidence: 56%

“…Time to progression was taken from the date of randomisation to the date of the progression. A 1-year survival of 40% had been reported for ACE in a recent MRC study (Thatcher et al, 2000). The North American experience suggested a 1-year survival rate of approximately 60% for a platinum-based combination, possibly in a more favourable patient group (Evans et al, 1987).…”

Section: Statistical Designmentioning

confidence: 90%

“…Median survivals of 9-11 months with 1-year survival of 30-40% were reported in trials of both LD and ED patients with good PS (Giaccone et al, 1993;Thatcher et al, 2000;Urban et al, 1999). However, treatment with ACE was associated with significant neutropenia that contributed to infection-related morbidity and mortality (Bunn et al, 1986;Postmus et al, 1996;Thatcher et al, 2000). Cisplatin and etoposide (PE) were widely used in North America, with similar survival rates to those reported for cyclophosphamide, doxorubicin, vincristine (CAV) (Fukuoka et al, 1991;Roth et al, 1992).…”

mentioning

confidence: 99%

“…The ACE combination was still widely used in Europe (Thatcher et al, 2000;Sambrook and Girling, 2001) and was a reference regimen for the European Organisation for Research and Treatment of Cancer (EORTC) Lung Group (Ardizzoni et al, 2002;Giaccone et al, 1993;Postmus et al, 1996). Median survivals of 9-11 months with 1-year survival of 30-40% were reported in trials of both LD and ED patients with good PS (Giaccone et al, 1993;Thatcher et al, 2000;Urban et al, 1999). However, treatment with ACE was associated with significant neutropenia that contributed to infection-related morbidity and mortality (Bunn et al, 1986;Postmus et al, 1996;Thatcher et al, 2000).…”

mentioning

confidence: 99%

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Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer

et al. 2008

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This randomised trial compared platinum-based to anthracycline-based chemotherapy in patients with small-cell lung cancer (limited or extensive stage) and p2 adverse prognostic factors. Patients were randomised to receive six cycles of either ACE (doxorubicin 50 mg/m 2 i.v., cyclophosphamide 1 g/m 2 i.v. and etoposide 120 mg/m 2 i.v. on day 1, then etoposide 240 mg/m 2 orally for 2 days) or PE (cisplatin 80 mg/m 2 and etoposide 120 mg/m 2 i.v. on day 1, then etoposide 240 mg/m 2 orally for 2 days) given for every 3 weeks. For patients where cisplatin was not suitable, carboplatin (AUC6) was substituted. A total of 280 patients were included (139 ACE, 141 PE). The response rates were 72% for ACE and 77% for PE. One-year survival rates were 34 and 38% (P ¼ 0.497), respectively and 2-year survival was the same (12%) for both arms. For LD patients, the median survival was 10.9 months for ACE and 12.6 months for PE (P ¼ 0.51); for ED patients median survival was 8.3 months and 7.5 months, respectively. More grades 3 and 4 neutropenia (90 vs 57%, Po0.005) and grades 3 and 4 infections (73 vs 29%, Po0.005) occurred with ACE, resulting in more days of hospitalisation and greater i.v. antibiotic use. ACE was associated with a higher risk of neutropenic sepsis than PE and with a trend towards worse outcome in patients with LD, and should not be studied further in this group of patients.

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