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Maintenance chemotherapy for ovarian cancer

  1. Ling Mei1,
  2. Hui Chen1,
  3. Dong Mei Wei1,
  4. Fang Fang1,*,
  5. Guan J Liu2,
  6. Huan Yu Xie3,
  7. Xun Wang1,
  8. Juan Zou1,
  9. Xu Han1,
  10. Dan Feng1

Editorial Group: Cochrane Gynaecological Cancer Group

Published Online: 29 JUN 2013

Assessed as up-to-date: 21 NOV 2012

DOI: 10.1002/14651858.CD007414.pub3


How to Cite

Mei L, Chen H, Wei DM, Fang F, Liu GJ, Xie HY, Wang X, Zou J, Han X, Feng D. Maintenance chemotherapy for ovarian cancer. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD007414. DOI: 10.1002/14651858.CD007414.pub3.

Author Information

  1. 1

    West China Second University Hospital, West China Women's and Children's Hospital, Department of Obstetrics and Gynecology, Chengdu, Sichuan, China

  2. 2

    West China Hospital, Sichuan University, Chinese Cochrane Centre, Chinese Evidence-Based Medicine Centre, Chengdu, Sichuan, China

  3. 3

    People's Hospital of Deyang City, Department of Obstetrics and Gynecology, Deyang, Sichuan, China

*Fang Fang, Department of Obstetrics and Gynecology, West China Second University Hospital, West China Women's and Children's Hospital, No. 17, Section Three, Ren Min Nan Lu Avenue, Chengdu, Sichuan, 610041, China. ffmn59@163.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 29 JUN 2013

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Characteristics of included studies [ordered by study ID]
Bolis 2006

MethodsRCT


Participants138 women with epithelial ovarian cancer achieved PCR or CCR

Stage 2c, 3 and 4

Mean age was 55.6 years old

Median follow-up time was 40 months


InterventionsEpidoxorubicin versus observation


Outcomes3-year overall survival and 5-year overall survival; toxic events


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated list

Allocation concealment (selection bias)Low riskQuote: "..according to a computer-generated list, by phone at the coordinating center"
Comment: Probably done.

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasLow riskThe study appears to be free of other sources of bias

Cheng 2006

MethodsRCT


Participants44 women with epithelial ovarian cancer achieved CCR

Stage 3 and 4

Mean age was 53.8 years old in maintenance chemotherapy group and 53.7 in observation group

Mean follow-up time was 39.6 months in maintenance chemotherapy group and 33.2 months in observation group


InterventionsPlatin + CTX/Taxel versus observation


OutcomesRecurrence rate, disease-free survival


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: " patients were randomly allocated"

Comment: Probably done

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasLow riskThe study appears to be free of other sources of bias

Mannel 2011

MethodsRCT


Participants542 women with early stage of epithelial ovarian cancer.

stage ⅠA or B grade 3 or clear cell subtype, or any stage IC, or stage II disease.

Mean age was 55.1 years old in maintenance chemotherapy group and 56 in observation group

Mean follow-up time was 6.7 years


InterventionsWeekly paclitaxel 40mg/m² × 24 weeks versus observation


OutcomesOverall survival, progression-free survival


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "treatment was randomly assigned through the GOG Statistical and Data Center prior to receiving any chemotherapy."

Comment: Probably done

Allocation concealment (selection bias)Low riskQuote: "The treatment assignment was not revealed until after the patient was successfully registered onto the study"

Comment: Probably done

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "18 patients randomized to the additional 24 weeks of paclitaxel withdrew during the follow-up,14 patients of the control group withdrew during the follow-up."

Comment: It is balanced between the two groups

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasLow riskThe study appears to be free of other sources of bias

Nicoletto 2004

MethodsRCT


Participants122 women with epithelial ovarian cancer achieved PCR

Stage 1c, 2b, 2c, 3 and 4

Mean age was 55 years old

Median follow-up time was not reported


Interventions5-Fu + cisplatin versus observation


Outcomes3-year overall survival and 3-year progression-free survival; toxic events


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "…at time of randomization"

Comment: Probably done

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "one patient refused treatment entirely after randomization and is therefore not evaluable"

Comment: For OS and PFS, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate.

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasLow riskThe study appears to be free of other sources of bias

Pecorelli 2009

MethodsRCT


Participants200 women with epithelial ovarian cancer

Stage ⅡB-Ⅳ with PCR or CCR

Mean age was 59 years old in maintenance chemotherapy group and 58 in observation group

Median follow-up time was 43.5 months


Interventions6 cycles of paclitaxel 175mg/m² every 3 weeks versus observation


OutcomesOverall survival and progression-free survival


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "A system of random permuted blocks within strata was used."

Comment: Comment: Probably done

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "6% never started treatment, and a total of 17% stopped treatment early because of toxicity (9%), progression/death (3%), patient refusal (3%), or other reasons (2%)."

Comment: For OS and PFS, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate.

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasLow riskThe study appears to be free of other sources of bias

Piccart 2003

MethodsRCT


Participants153 women with ovarian cancer achieved PCR

Stage 2b, 2c, 3 and 4

Mean age was 55 years old

Median follow-up time was 96.7 months


InterventionsCisplatin versus observation


Outcomes3, 5, 8, 10-year OS and PFS; toxic events


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "randomization took place…"

Comment: Probably done

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "one patient no follow-up forms. No statistically significant difference between the two groups"

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasHigh riskQuote: "the study was closed prematurely in view of a disappointing recruitment rate…"

Placido 2004

MethodsRCT


Participants273 women with epithelial ovarian cancer achieved CCR or partial clinical remission

Stage 1c, 2, 3 and 4

Mean age was 55 years old in maintenance chemotherapy group and 56 in observation group

Median follow-up time was 28 months


InterventionsTopotecan versus observation; toxic events


Outcomes1-year PFS


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "…by means of a computer-driven minimization procedure"

Comment: Probably done

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasLow riskThe study appears to be free of other sources of bias

Sorbe 2003

MethodsRCT


Participants172 women with epithelial ovarian cancer achieved PCR and CCR

Stage 3 and 4

Mean age was 55 years old

Median follow-up time was not reported


InterventionsCisplatin + doxorubicin/epidoxorubicin versus observation


Outcomes3, 5, 10-year OS and PFS; toxic events


NotesThis study is a 3-arm study comparing maintenance chemotherapy, maintenance radiotherapy and no further treatment. The total partIcipants are 172 women with 98 of PCR and 74 of CCR. The women with PCR were divided into chemotherapy, radiotherapy and observation groups while the women with CCR were divided into chemotherapy and radiotherapy groups.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients…were entered in a prospective, randomized, multicenter trial"

Comment: Probably done

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement

Blinding (performance bias and detection bias)
All outcomes
Low riskNo blinding, but the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll expected outcomes were reported

Other biasLow riskThe study appears to be free of other sources of bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Abaid 2010The follow-up of Markman 2003 and the results were of high potential bias

Cure 2001It compared high dose chemotherapy combined with PBSC versus normal dose maintenance chemotherapy

Lesnock 2011A cost-effect analysis of three GOG studies

Mannel 2010The same trial with the Mannel 2011 but not the final result

Markman 2003It compared short- versus long-duration maintenance chemotherapy

Markman 2009The follow-up of Markman 2003 and the results were of high potential bias

Scarfone 2002The original article or data are unavailable

 
Characteristics of ongoing studies [ordered by study ID]
NCT00108745

Trial name or titlePaclitaxel or polyglutamate paclitaxel or observation in treating women with stage III or stage IV ovarian epithelial or peritoneal cancer

MethodsRCT

ParticipantsWomen with advanced ovarian or primary peritoneal cancer who achieve a complete clinical response to primary platinum/taxane chemotherapy

Interventions
  • Arm I: women receive polyglutamate paclitaxel IV over 10-20 minutes on day 1.
  • Arm II: women receive paclitaxel IV over 3 hours on day 1.
  • Arm III: women receive no further anticancer treatment until evidence of disease progression.


In arms I and II, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity

OutcomesPrimary outcome measures: overall survival

Secondary outcome measures: Peripheral neuropathy by Gynecologic Oncology Group (GOG) NTX4 at 6 months after study enrolment
General quality of life by Functional Assessment of Cancer Therapy-Ovarian-Trial Outcome Index (FACT-O-TOI) at 6 months after study enrolment
Exploratory assessment of several tissue and serum angiogenic markers for prognosis by immunohistochemistry and antibody array prior to treatment in courses 1 and 2
Exploratory time-dependent assessment of quality of life and peripheral neuropathy by FACT-O-TOI and GOG-NTX4 monthly during year 1 and then every 3 months for 2 years

Starting dateMarch 2005

Contact informationStudy Chair: Maurie Markman, MD; M.D. Anderson Cancer Center

Notes

 
Comparison 1. Maintenance chemotherapy versus observation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 3-year PFS4541Risk Ratio (M-H, Fixed, 95% CI)1.07 [0.91, 1.25]

 2 5-year PFS3761Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.97, 1.17]

 3 10-year PFS2219Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.65, 1.41]

 4 3-year OS5679Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.92, 1.08]

 5 5-year OS4899Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.96, 1.10]

 6 10-year OS2219Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.78, 1.49]

 
Comparison 2. Platin-based maintenance chemotherapy versus observation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 3-year PFS3341Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.86, 1.24]

 2 5-year PFS2219Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.88, 1.58]

 3 10-year PFS2219Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.65, 1.41]

 4 3-year OS3341Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.94, 1.18]

 5 5-year OS2219Risk Ratio (M-H, Fixed, 95% CI)1.07 [0.88, 1.31]

 6 10-year OS2219Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.78, 1.49]

 
Comparison 3. Doxorubicin-based maintenance chemotherapy versus observation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 3-year OS2204Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.86, 1.15]

 2 5-year OS2204Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.79, 1.27]

 
Comparison 4. Maintenance chemotherapy versus maintenance radiotherapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 3-year PFS1141Risk Ratio (M-H, Fixed, 95% CI)1.07 [0.75, 1.54]

    1.1 PCR
167Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.50, 1.11]

    1.2 CCR
174Risk Ratio (M-H, Fixed, 95% CI)2.14 [0.99, 4.64]

 2 5-year PFS1141Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.55, 1.37]

    2.1 PCR
167Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.39, 1.12]

    2.2 CCR
174Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.59, 3.79]

 3 10-year PFS1141Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.51, 1.55]

    3.1 PCR
167Risk Ratio (M-H, Fixed, 95% CI)0.51 [0.27, 1.00]

    3.2 CCR
174Risk Ratio (M-H, Fixed, 95% CI)4.0 [0.91, 17.59]

 4 3-year OS1141Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.85, 1.32]

    4.1 PCR
167Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.72, 1.16]

    4.2 CCR
174Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.84, 1.94]

 5 5-year OS1141Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.70, 1.35]

    5.1 PCR
167Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.57, 1.20]

    5.2 CCR
174Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.68, 2.29]

 6 10-year OS1141Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.58, 1.52]

    6.1 PCR
167Risk Ratio (M-H, Fixed, 95% CI)0.70 [0.41, 1.20]

    6.2 CCR
174Risk Ratio (M-H, Fixed, 95% CI)2.0 [0.66, 6.07]