Neoadjuvant chemotherapy for locally advanced cervical cancer:: a systematic review and meta-analysis of individual patient data from 21 randomised trials

被引:235
|
作者
Benedetti-Panici, P
Bermudez, A
Blake, P
Cárdenas, J
Chang, TC
Chiara, S
Di Paola, G
Floquet, A
Guthrie, D
Kigawa, J
Kumar, L
Leborgne, F
Lodge, N
Poole, C
Sardi, J
Souhami, L
Sundfor, K
Symonds, P
Tattersall, M
Greggi, S
Guthrie, D
Parker, V
Parmar, MKB
Sardi, J
Stewart, LA
Tierney, JF
机构
[1] MRC, Clin Trials Unit, Meta Anal Grp, London NW1 2DA, England
[2] Libera Univ Campus Biomed Roma, Rome, Italy
[3] Univ Buenos Aires, Buenos Aires, DF, Argentina
[4] Royal Marsden Hosp, London SW3 6JJ, England
[5] Ctr Estatal Cancerol, Colima, Mexico
[6] Chang Gung Mem Hosp, Linkou, Taiwan
[7] Ist Nazl Ric Canc, I-16132 Genoa, Italy
[8] Inst Bergonie, Bordeaux, France
[9] Derbyshire Royal Infirm, Derby DE1 2QY, England
[10] Tottori Univ, Sch Med, Yonago, Tottori 683, Japan
[11] All India Inst Med Sci, New Delhi, India
[12] Hosp Pereira Rossell, Montevideo, Uruguay
[13] City Hosp Birmingham, Birmingham, W Midlands, England
[14] Hop Gen Montreal, Montreal, PQ, Canada
[15] Norwegian Radium Hosp, Oslo, Norway
[16] Leicester Royal Infirm, Leicester, Leics, England
[17] Univ Sydney, Sydney, NSW 2006, Australia
[18] Ist Nazl Tumori, Fdn G Pascale, Naples, Italy
[19] COU RAGE UK, Manchester, Lancs, England
关键词
systematic review; meta-analysis; individual patient data; cervical neoplasms; drug therapy; chemotherapy; adjuvant; neoadjuvant;
D O I
10.1016/S0959-8049(03)00425-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Despite the enrolment of more than 3000 women in randomised trials, the benefits and risks of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer remain uncertain. We carried out a systematic review and meta-analysis of individual patient data to assess the effect of neoadjuvant chemotherapy in two comparisons. In the first comparison, of neoadjuvant chemotherapy followed by radical radiotherapy compared with the same radiotherapy alone, we obtained data from 18 trials and 2074 patients. When all trials were considered together, a high level of statistical heterogeneity suggested that the results could not be combined indiscriminately. A substantial amount of heterogeneity was explained by separate analyses of groups of trials. Trials using chemotherapy cycle lengths of 14 days and shorter (Hazard Ratio (HR)) =0.83, 95% Confidence Interval (CI) = 0.69-1.00, P= 0.046) or cisplatin dose intensities greater than or equal to 25 mg/m(2) per week (HR = 0.91, 95% Cl = 0.78-1.05, P=0.20) tended to show an advantage for neoadjuvant chemotherapy on survival. In contrast, trials using cycle lengths longer than 14 days (HR = 1.25, 95% Cl = 1.07-1.46, P= 0.005) or cisplatin dose intensities lower than 25mg/m(2) per week (HR = 1.35, 95% Cl = 1.11-1. 14, P= 0.002) tended to show a detrimental effect of neoadjuvant chemotherapy on survival. In the second comparison, of neoadjuvant chemotherapy followed by surgery compared with radical radiotherapy alone, data from 5 trials and 872 patients were obtained. The combined results from all trials (HR = 0.65, 95% Cl = 0.53-0.80, P= 0.0004) indicated a highly significant reduction in the risk of death with neoadjuvant chemotherapy, but there were some differences between the trials in their design and results. Despite some unexplained heterogeneity, the timing and dose intensity of cisplatin-based neoadjuvant chemotherapy appears to have an important impact on whether or not it benefits women with locally advanced cervical cancer and warrants further exploration. (C) 2003 Elsevier Ltd. All rights reserved.
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收藏
页码:2470 / 2486
页数:17
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