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PMID- 17938703
DA  - 20071016
DCOM- 20100205
LR  - 20130523
IS  - 1198-0052 (Print)
IS  - 1198-0052 (Linking)
VI  - 14
IP  - 5
DP  - 2007 Oct
TI  - Optimal chemotherapy treatment for women with recurrent ovarian cancer.
PG  - 195-208
AB  - QUESTION: What is the optimal chemotherapy treatment for women with recurrent
      ovarian cancer who have previously received platinum-based chemotherapy?
      PERSPECTIVES: Currently, standard primary therapy for advanced disease involves a
      combination of maximal cytoreductive surgery and chemotherapy with carboplatin
      plus paclitaxel or with carboplatin alone. Despite initial high response rates, a
      large proportion of patients relapse, resulting in a therapeutic challenge.
      Because these patients are not curable, the goal of therapy becomes improvement
      in both quality and length of life. The search has therefore been to find active 
      agents for women with recurrent disease following platinum-based chemotherapy.
      OUTCOMES: Outcomes of interest included any combination of tumour response rate, 
      progression-free survival, overall survival, adverse events, and quality of life.
      METHODOLOGY: The MEDLINE, EMBASE, and Cochrane Library databases were
      systematically searched for primary articles and practice guidelines. The
      resulting evidence informed the development of clinical practice recommendations.
      The systematic review and recommendations were approved by the Report Approval
      Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease
      Site Group (DSG). The practice guideline was externally reviewed by a sample of
      practitioners from Ontario, Canada. RESULTS: Thirteen randomized trials compared 
      various chemotherapy regimens for patients with recurrent ovarian cancer. In five
      of the thirteen trials in which 100% of patients were considered sensitive to
      platinum-containing chemotherapy, further platinum-based combination chemotherapy
      significantly improved response rates (two trials), progression-free survival
      (four trials), and overall survival (three trials) when compared with
      single-agent chemotherapy involving carboplatin or paclitaxel. Only two of these 
      randomized trials compared the same chemotherapy regimens: carboplatin alone
      versus the combination of carboplatin and paclitaxel. Both trials were consistent
      in reporting improved survival outcomes with the combination of carboplatin and
      paclitaxel. In one trial, the combination of carboplatin and gemcitabine resulted
      in significantly higher response rates and improved progression-free survival
      when compared with carboplatin alone. Median survival with carboplatin alone
      ranged from 17 months to 24 months in four trials. In eight of the thirteen
      trials in which 35%-100% of patients had platinum-refractory or -resistant
      disease, one trial reported a statistically significant 2-month improvement in
      overall survival with liposomal doxorubicin as compared with topotecan (15 months
      vs. 13 months, p = 0.038; hazard ratio: 1.23; 95% confidence interval: 1.01 to
      1.50). In that trial, because of the limited clinical benefit and the unusual
      finding that a survival difference emerged only after a year of treatment with no
      corresponding improvement in the rate of response or of progression-free
      survival, the authors concluded that further confirmation by results from
      randomized trials were needed to establish the superiority of one agent over
      another in their trial. In one trial, topotecan was superior to treosulphan in
      patient progression-free survival by a span of approximately 2 months (5.4 months
      vs. 3.0 months, p < 0.001). Toxicity was reported in all of the randomized
      trials, and although data on adverse events varied by treatment regimen, the
      observed adverse events correlated with known toxicity profiles. As expected,
      combination chemotherapy was associated with higher rates of adverse events.
      PRACTICE GUIDELINE: TARGET POPULATION: This clinical recommendation applies to
      women with recurrent epithelial ovarian cancer who have previously received
      platinum-based chemotherapy. Of specific interest are women who have previously
      shown sensitivity to platinum therapy and those who previously were refractory or
      resistant to platinum-based chemotherapy. As a general categorization within what
      is actually a continuum, "platinum sensitivity" refers to disease recurrence 6
      months or more after prior platinum-containing chemotherapy, and "platinum
      resistance" refers to a response to platinum-based chemotherapy followed by
      relapse less than 6 months after chemotherapy is stopped. "Platinum-refractory
      disease" refers to a lack of response or to progression while on platinum-based
      chemotherapy. RECOMMENDATIONS: Although the body of evidence that informs the
      clinical recommendations is based on randomized trial data, those data are
      incomplete. Based on the available data and expert consensus opinion, the
      Gynecology Cancer DSG makes these recommendations: Systemic therapy for recurrent
      ovarian cancer is not curative. It is therefore recognized that each patient must
      be individually assessed to determine optimal therapy in terms of recurrence,
      sensitivity to platinum, toxicity, ease of administration, and patient
      preference. All suitable patients should be offered the opportunity to
      participate in randomized trials, if available.In the absence of
      contraindications, combination platinum-based chemotherapy should be considered
      for patients with prior sensitivity to platinum-containing chemotherapy. As
      compared with carboplatin alone, the combination of carboplatin and paclitaxel
      significantly improved both progression-free and overall survival.If combination 
      platinum-based chemotherapy is not indicated, then a single platinum agent should
      be considered. Carboplatin has demonstrated efficacy across trials and has a
      manageable toxicity profile.If a single platinum agent is not being considered,
      then monotherapy with paclitaxel, topotecan, or pegylated liposomal doxorubicin
      are seen as reasonable treatment options.Some patients may be repeatedly
      sensitive to treatment and may benefit from multiple lines of chemotherapy.For
      patients with platinum-refractory or platinum-resistant disease, the goals of
      treatment should be to improve quality of life by extending the symptom-free
      interval, by reducing symptom intensity, and by increasing progression-free
      interval, and, if possible, to prolong life.With non-platinum agents, monotherapy
      should be considered because no advantage appears to accrue to the use of
      non-platinum-containing combination chemotherapy in this group of patients.
      Single-agent paclitaxel, topotecan, or pegylated liposomal doxorubicin have
      demonstrated activity in this patient population and are reasonable treatment
      options.No evidence either supports or refutes the use of more than one line of
      chemotherapy in patients with platinum-refractory or platinum-resistant
      recurrence. Many treatment options have shown modest response rates, but their
      benefits over best supportive care have not been studied in clinical trials.
FAU - Fung-Kee-Fung, M
AU  - Fung-Kee-Fung M
AD  - The Ottawa Hospital Regional Cancer Centre, Ottawa, Ontario.
FAU - Oliver, T
AU  - Oliver T
FAU - Elit, L
AU  - Elit L
FAU - Oza, A
AU  - Oza A
FAU - Hirte, H W
AU  - Hirte HW
FAU - Bryson, P
AU  - Bryson P
PT  - Journal Article
PL  - Canada
TA  - Curr Oncol
JT  - Current oncology (Toronto, Ont.)
JID - 9502503
PMC - PMC2002482
OID - NLM: PMC2002482
OT  - Chemotherapy
OT  - drug therapy
OT  - ovarian cancer
OT  - ovarian neoplasms
OT  - practice guideline
OT  - systematic review
EDAT- 2007/10/17 09:00
MHDA- 2007/10/17 09:01
CRDT- 2007/10/17 09:00
PST - ppublish
SO  - Curr Oncol. 2007 Oct;14(5):195-208.

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