Maintenance chemotherapy for ovarian cancer

Background

Of all the gynaecological cancers, ovarian cancer has the highest death rate and epithelial ovarian cancer accounts for about 90% of all cases. Surgery and six courses of platinum-based chemotherapy is the standard treatment and 75% of the women may not have any evidence of disease at the end of this treatment. However, 75% of the women who respond to initial treatment will relapse within 18 to 28 months and only 20% to 40% of all women will survive beyond five years.Some doctors suggest giving maintenance chemotherapy for epithelial ovarian cancer. Maintenance chemotherapy refers to the chemotherapy given to women who have achieved remission after initial surgery and induction chemotherapy.The aim of maintenance chemotherapy is to prolong the duration of remission and improve the overall length of survival. Some studies indicate that maintenance chemotherapy can improve the time without cancer progression, while others do not show any effect.

The aim of the review

The aim of this review was to estimate whether using maintenance chemotherapy is better than observation alone for women with epithelial ovarian cancer.

What are the main findings?

We identified eight trials that used different types of chemotherapy (e.g. platinum agents, doxorubicin, topotecan or paclitaxel) but there was not sufficient evidence to prove any of the drugs were better than observation alone. An important consideration for women with advanced disease is the balance between the benefit of treatment and the harms or adverse effects that these treatments may cause. There were insufficient data to comment on the overall impact of the maintenance chemotherapy on clinical benefit from the women's perspective.

Quality of the evidence

We tried to identify all trials and both published and unpublished data in this review; thereby minimising the influence of publication bias. The included trials are graded as moderate quality but this meta-analysis currently provides a reliable assessment of the average treatment effect of platinum and doxorubicin among women with advanced epithelial ovarian cancer.

What are the conclusions?

Use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy has not proved effective to prolong the life time of women with epithelial ovarian cancer. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required.

Authors' conclusions: 

There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required.

Read the full abstract...
Background: 

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum-based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer.

Objectives: 

To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL).

Search strategy: 

In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017.

Selection criteria: 

Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy.

Data collection and analysis: 

Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression-free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention-to-treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs.

Main results: 

No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta-analysis indicated no significant difference in three-, five- and 10-year OS or PFS. For five-year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate-certainly evidence) and for the five-year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate-certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10-year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three- and five-year OS rates have no significant difference between the two groups.

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