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Chemotherapy for advanced gastric cancer.

Abstract Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen.
PMID
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Chemotherapy for advanced gastric cancer.

Chemotherapy for advanced gastric cancer.

Authors

Mayor MeshTerms
Keywords
Journal Title the cochrane database of systematic reviews
Publication Year Start




PMID- 28850174
OWN - NLM
STAT- MEDLINE
DCOM- 20170920
LR  - 20171116
IS  - 1469-493X (Electronic)
IS  - 1361-6137 (Linking)
VI  - 8
DP  - 2017 Aug 29
TI  - Chemotherapy for advanced gastric cancer.
PG  - CD004064
LID - 10.1002/14651858.CD004064.pub4 [doi]
AB  - BACKGROUND: Gastric cancer is the fifth most common cancer worldwide. In
      "Western" countries, most people are either diagnosed at an advanced stage, or
      develop a relapse after surgery with curative intent. In people with advanced
      disease, significant benefits from targeted therapies are currently limited to
      HER-2 positive disease treated with trastuzumab, in combination with
      chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination
      with paclitaxel, demonstrated significant survival benefits. Thus, systemic
      chemotherapy remains the mainstay of treatment for advanced gastric cancer.
      Uncertainty remains regarding the choice of the regimen. OBJECTIVES: To assess
      the efficacy of chemotherapy versus best supportive care (BSC), combination
      versus single-agent chemotherapy and different chemotherapy combinations in
      advanced gastric cancer. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference
      lists of studies, and contacted pharmaceutical companies and experts to identify 
      randomised controlled trials (RCTs). SELECTION CRITERIA: We considered only RCTs 
      on systemic, intravenous or oral chemotherapy versus BSC, combination versus
      single-agent chemotherapy and different chemotherapy regimens in advanced gastric
      cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently identified
      studies and extracted data. A third investigator was consulted in case of
      disagreements. We contacted study authors to obtain missing information. MAIN
      RESULTS: We included 64 RCTs, of which 60 RCTs (11,698 participants) provided
      data for the meta-analysis of overall survival. We found chemotherapy extends
      overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio
      (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three
      studies, moderate-quality evidence). Combination chemotherapy extends OS slightly
      (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79
      to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is
      partly counterbalanced by increased toxicity. The benefit of epirubicin in
      three-drug combinations, in which cisplatin is replaced by oxaliplatin and 5-FU
      is replaced by capecitabine is unknown.Irinotecan extends OS slightly (by an
      additional 1.6 months) versus non-irinotecan-containing regimens (HR 0.87, 95% CI
      0.80 to 0.95, 2135 participants, 10 studies, high-quality evidence).Docetaxel
      extends OS slightly (just over one month) compared to non-docetaxel-containing
      regimens (HR 0.86, 95% CI 0.78 to 0.95, 2001 participants, eight studies,
      high-quality evidence). However, due to subgroup analyses, we are uncertain
      whether docetaxel-containing combinations (docetaxel added to a single-agent or
      two-drug combination) extends OS due to moderate-quality evidence (HR 0.80, 95%
      CI 0.71 to 0.91, 1466 participants, four studies, moderate-quality evidence).
      When another chemotherapy was replaced by docetaxel, there is probably little or 
      no difference in OS (HR 1.05; 0.87 to 1.27, 479 participants, three studies,
      moderate-quality evidence). We found there is probably little or no difference in
      OS when comparing capecitabine versus 5-FU-containing regimens (HR 0.94, 95% CI
      0.79 to 1.11, 732 participants, five studies, moderate-quality evidence)
      .Oxaliplatin may extend (by less than one month) OS versus cisplatin-containing
      regimens (HR 0.81, 95% CI 0.67 to 0.98, 1105 participants, five studies,
      low-quality evidence). We are uncertain whether taxane-platinum combinations with
      (versus without) fluoropyrimidines extend OS due to very low-quality evidence (HR
      0.86, 95% CI 0.71 to 1.06, 482 participants, three studies, very low-quality
      evidence). S-1 regimens improve OS slightly (by less than an additional month)
      versus 5-FU-containing regimens (HR 0.91, 95% CI 0.83 to 1.00, 1793 participants,
      four studies, high-quality evidence), however since S-1 is used in different
      doses and schedules between Asian and non-Asian population, the applicability of 
      this finding to individual populations is uncertain. AUTHORS' CONCLUSIONS:
      Chemotherapy improves survival (by an additional 6.7 months) in comparison to
      BSC, and combination chemotherapy improves survival (by an additional month)
      compared to single-agent 5-FU. Testing all patients for HER-2 status may help to 
      identify patients with HER-2-positive tumours, for whom, in the absence of
      contraindications, trastuzumab in combination with capecitabine or 5-FU in
      combination with cisplatin has been shown to be beneficial. For HER-2 negative
      people, all different two-and three-drug combinations including irinotecan,
      docetaxel, oxaliplatin or oral 5-FU prodrugs are valid treatment options for
      advanced gastric cancer, and consideration of the side effects of each regimen is
      essential in the treatment decision. Irinotecan-containing combinations and
      docetaxel-containing combinations (in which docetaxel was added to a single-agent
      or two-drug (platinum/5-FUcombination) show significant survival benefits in the 
      comparisons studied above. Furthermore, docetaxel-containing three-drug regimens 
      have increased response rates, but the advantages of the docetaxel-containing
      three-drug combinations (DCF, FLO-T) are counterbalanced by increased toxicity.
      Additionally, oxaliplatin-containing regimens demonstrated a benefit in OS as
      compared to the same regimen containing cisplatin, and there is a modest survival
      improvement of S-1 compared to 5-FU-containing regimens.Whether the survival
      benefit for three-drug combinations including cisplatin, 5-FU, and epirubicin as 
      compared to the same regimen without epirubicin is still valid when second-line
      therapy is routinely administered and when cisplatin is replaced by oxaliplatin
      and 5-FU by capecitabine is questionable. Furthermore, the magnitude of the
      observed survival benefits for the three-drug regimens is not large enough to be 
      clinically meaningful as defined recently by the American Society for Clinical
      Oncology (Ellis 2014). In contrast to the comparisons in which a survival benefit
      was observed by adding a third drug to a two-drug regimen at the cost of
      increased toxicity, the comparison of regimens in which another chemotherapy was 
      replaced by irinotecan was associated with a survival benefit (of borderline
      statistical significance), but without increased toxicity. For this reason
      irinotecan/5-FU-containing combinations are an attractive option for first-line
      treatment. Although they need to be interpreted with caution, subgroup analyses
      of one study suggest that elderly people have a greater benefit form oxaliplatin,
      as compared to cisplatin-based regimens, and that people with locally advanced
      disease or younger than 65 years might benefit more from a three-drug regimen
      including 5-FU, docetaxel, and oxaliplatin as compared to a two-drug combination 
      of 5-FU and oxaliplatin, a hypothesis that needs further confirmation. For people
      with good performance status, the benefit of second-line chemotherapy has been
      established in several RCTs.
FAU - Wagner, Anna Dorothea
AU  - Wagner AD
AD  - Department of Oncology, Lausanne University Hospitals and Clinics, Rue du Bugnon 
      46, Lausanne, Switzerland, 1011.
FAU - Syn, Nicholas Lx
AU  - Syn NL
FAU - Moehler, Markus
AU  - Moehler M
FAU - Grothe, Wilfried
AU  - Grothe W
FAU - Yong, Wei Peng
AU  - Yong WP
FAU - Tai, Bee-Choo
AU  - Tai BC
FAU - Ho, Jingshan
AU  - Ho J
FAU - Unverzagt, Susanne
AU  - Unverzagt S
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170829
PL  - England
TA  - Cochrane Database Syst Rev
JT  - The Cochrane database of systematic reviews
JID - 100909747
RN  - 0 (Anthracyclines)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (docetaxel)
RN  - 7673326042 (irinotecan)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U3P01618RT (Fluorouracil)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
UOF - Cochrane Database Syst Rev. 2010 Mar 17;(3):CD004064. PMID: 20238327
MH  - Anthracyclines/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Camptothecin/administration & dosage/analogs & derivatives
MH  - Cisplatin/administration & dosage
MH  - Fluorouracil/administration & dosage
MH  - Humans
MH  - Randomized Controlled Trials as Topic
MH  - Stomach Neoplasms/*drug therapy/mortality
MH  - Taxoids/administration & dosage
EDAT- 2017/08/30 06:00
MHDA- 2017/09/21 06:00
CRDT- 2017/08/30 06:00
PHST- 2017/08/30 06:00 [pubmed]
PHST- 2017/09/21 06:00 [medline]
PHST- 2017/08/30 06:00 [entrez]
AID - 10.1002/14651858.CD004064.pub4 [doi]
PST - epublish
SO  - Cochrane Database Syst Rev. 2017 Aug 29;8:CD004064. doi:
      10.1002/14651858.CD004064.pub4.