Repositorio
Institucional

Pelayo Alvarez, Marta

Westeel, Virginie

Cortes-Jofre, Marcela

Bonfill Cosp, Xavier

Chemotherapy versus best supportive care for extensive small cell lung cancer

WILEY

COCHRANE DATABASE OF SYSTEMATIC REVIEWS

en

Background Combination chemotherapy has been the mainstay of treatment for extensive stage small celI lung cancer (SCLC) over the last 30 years, even though it only gives a short prolongation in median survival time. The main goal for these patients should be palliation with the aim of improving their quality of life. Objectives To determine the effectiveness of first-line chemotherapy versus placebo or best supportive care (BSC) in prolonging survival in patients with extensive SCLC at diagnosis and the effectiveness of second-line chemotherapy at relapse or progression after first-line chemotherapy compared with BSC or placebo in prolonging survival in patients with extensive SCLC; as well as to evaluate the adverse events of treatment and the quality of life of patients. Search methods This is the second update of the review. MEDLINE (1966 to October 2013), EMBASE (1974 to October 2013), and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 3) were searched. Experts in the field were contacted. Selection criteria Phase III randomised controlled trials in which any chemotherapy treatment was compared with placebo or BSC in patients with extensive SCLC, as first-line or second-line therapy at relapse. Data collection and analysis Two authors independently extracted data and assessed study quality. We resolved disagreements by discussion. Additional information was obtained from one study author. Main results Two studies of unclear risk of bias were included for first-line chemotherapy. A total of 88 men under 70 years with good performance status were randomised to receive either supportive care, placebo infusion or ifosfamide. Ifosfamide gave an extra mean survival of 78.5 days compared with supportive care or placebo infusion. Partial tumour response was greater with the active treatment. Toxicity was only seen in the chemotherapy group and quality of life was only assessed at the beginning of treatment. The quality of the evidence for overall survival and adverse effects was very low. Three studies of moderate risk of bias were included for second-line chemotherapy at relapse (one identified in the last search). A total of 932 men and women under 75 years and any performance status were randomised to receive either methotrexate-doxorubicin, topotecan, or picoplatin versus symptomatic treatment or BSC. The methotrexate-doxorubicin treatment gave a median survival of 63 days longer than in the symptomatic-treatment group for patients allocated to receive four cycles of first-line chemotherapy, and 21 days longer for patients allocated to receive eight cycles of first-line chemotherapy. Treatment with topotecan gave a median survival of 84 days longer than in the BSC group (log-rank P = 0.01). The adjusted hazard ratio (HR) for overall survival was 0.61 (95% CI 0.43 to 0.87). Treatment with picoplatin gave a median survival time of six days longer than BSC (HR 0.817, 95% CI 0.65 to 1.03, P = 0.0895). A meta-analysis of topotecan and picoplatin gave a HR of 0.73 (95% CI 0.55 to 0.96, P = 0.03; low-quality evidence). Partial or complete response in the methotrexate-doxorubicin group was 22.3%. Five patients (7%, 95% CI 2.33 to 15.67) showed a partial response with topotecan. No data were provided about tumour response in the picoplatin study. Toxicity was worst in the chemotherapy group (moderate-quality evidence). Quality of life was better in the topotecan group and was not measured in the methotrexate-doxorubicin and picoplatin studies (low-quality evidence). Authors' conclusions Two small RCTs from the 1970s suggest that first-line chemotherapeutic treatment (based on ifosfamide) may provide a small survival benefit (less than three months) in comparison with supportive care or placebo infusion in patients with advanced SCLC. However platinum-based combination chemotherapy regimens have been shown to increase complete response rates when compared to nonplatinum chemotherapy regimens with no significant difference in survival, and so these are currently the standard first-line treatment for patients with SCLC. Second-line chemotherapy at relapse or progression may prolong survival for some weeks in relation to BSC. Nevertheless, the impact of first-line chemotherapy on quality of life, older patients, women and patients with poor prognosis is unknown and the benefits of second-line chemotherapy are also unclear for older people. Globally, the evidence on which these conclusions are based is very scarce and of uncertain or low quality, which calls for well-designed, controlled trials to further evaluate the trade-offs between benefits and risks of different chemotherapeutic schedules in patients with advanced SCLC.

Artículo de revisión

Internal sources Iberoamerican Cochrane Centre, Spain. External sources Instituto Carlos III (Contract no. 10035) Ministry of Health, Spain. In the initial review of 2003

Fuentes internas Centro Cochrane Iberoamericano, España. Fuentes externas Instituto Carlos III (Contrato nº 10035) Ministerio de Sanidad, España. En la revisión inicial de 2003

10.1002/14651858.CD001990.pub3

pdf

Antineoplastic Combined Chemotherapy Protocols [therapeutic use]

Carcinoma, Small Cell [drug therapy

pathology]

Lung Neoplasms [drug therapy

pathology]

Randomized Controlled Trials as Topic

Survival Analysis

Humans

QUALITY-OF-LIFE

PHASE-III TRIAL

KINGDOM COORDINATING COMMITTEE

RANDOMIZED CONTROLLED-TRIALS

MEDICAL-RESEARCH-COUNCIL

MAINTENANCE CHEMOTHERAPY

ELDERLY-PATIENTS

ORAL ETOPOSIDE

PROGNOSTIC-FACTORS

CLINICAL-TRIALS

Protocolos de quimioterapia combinada antineoplásica [uso terapéutico]

Carcinoma de células pequeñas [farmacoterapia

patología]

Neoplasias pulmonares [farmacoterapia

patología]

Ensayos controlados aleatorios como tema

Análisis de supervivencia

Humanos

CALIDAD DE VIDA

ENSAYO DE FASE III

COMITÉ COORDINADOR DEL REINO UNIDO

ENSAYOS CONTROLADOS ALEATORIZADOS

CONSEJO DE INVESTIGACIÓN MÉDICA

QUIMIOTERAPIA DE MANTENIMIENTO

PACIENTES ANCIANOS

ETOPÓSIDO ORAL

FACTORES PRONÓSTICOS

ENSAYOS CLÍNICOS

Antineoplastic Combined Chemotherapy Protocols [therapeutic use]

Carcinoma, Small Cell [drug therapy

pathology]

Lung Neoplasms [drug therapy

pathology]

Randomized Controlled Trials as Topic

Survival Analysis

Humans

QUALITY-OF-LIFE

PHASE-III TRIAL

KINGDOM COORDINATING COMMITTEE

RANDOMIZED CONTROLLED-TRIALS

MEDICAL-RESEARCH-COUNCIL

MAINTENANCE CHEMOTHERAPY

ELDERLY-PATIENTS

ORAL ETOPOSIDE

PROGNOSTIC-FACTORS

CLINICAL-TRIALS

Protocolos de quimioterapia combinada antineoplásica [uso terapéutico]

Carcinoma de células pequeñas [farmacoterapia

patología]

Neoplasias pulmonares [farmacoterapia

patología]

Ensayos controlados aleatorios como tema

Análisis de supervivencia

Humanos

CALIDAD DE VIDA

ENSAYO DE FASE III

COMITÉ COORDINADOR DEL REINO UNIDO

ENSAYOS CONTROLADOS ALEATORIZADOS

CONSEJO DE INVESTIGACIÓN MÉDICA

QUIMIOTERAPIA DE MANTENIMIENTO

PACIENTES ANCIANOS

ETOPÓSIDO ORAL

FACTORES PRONÓSTICOS

ENSAYOS CLÍNICOS

Oncología

Farmacología y Farmacia

Medicina General e Interna

Chemotherapy versus best supportive care for extensive small cell lung cancer

COCHRANE DATABASE OF SYSTEMATIC REVIEWS

hibrida

verde

acceso abierto

acceso abierto

PMID 24282143

en

Artículo de revisión

versión publicada

Iberoamerican Cochrane Centre, Spain#Instituto Carlos III, Ministry of Health, Spain 10035

Iberoamerican Cochrane Centre, Spain

Instituto Carlos III, Ministry of Health, Spain 10035

WILEY

1469-493X

CD001990

Medicina general e interna

Medicine, General & Internal

pdf

WOS:000327587400008