Epithelial ovarian cancer (EOC) is a potentially life-threatening condition. EOC usually develops in women above 50 years of age and is rarely seen in women younger than 35 years old. Early symptoms of the disease are usually mild and vague, making this disease difficult to detect at an early stage. Patients with EOC are relatively asymptomatic until the disease has progressed to an advanced stage.
Although EOC initially responds well to surgery and chemotherapy, there is a high rate of recurrence within 12 to 24 months of treatment. Interferons are proteins that are made and released by host cells in response to the presence of pathogens. They are named after their ability to 'interfere' with viral replication within host cells. Interferon serves two important functions. It signals neighbouring cells and triggers their resistance mechanisms; and it activates other immune cells that kill invading pathogens. This review assessed the effectiveness of interferon therapy in reducing the rate of recurrence or prolonging the time between chemotherapy and subsequent recurrence of the disease.
Five trials, including 1476 participants, were included in the review. Three of the five trials were stopped early. The risk of bias of most of the trials was high or unclear due to incomplete reporting of methods and results. Most of the trials were not large enough to detect any true effect of the intervention. Trials either did not report the results of important outcomes or the results of important outcomes were not uniform between the trials.
The evidence from the three trials suggested that the addition of interferon to first-line chemotherapy did not alter the overall survival in post-surgical women with advanced EOC compared with chemotherapy alone. On the contrary, there is evidence that interferon in combination with chemotherapy worsened progression free survival in post-surgical women with advanced EOC compared with chemotherapy alone. Furthermore, there is not enough evidence that interferon therapy alone improves overall survival or progression free survival in post-surgical women who have undergone first-line chemotherapy when compared with observation alone.
Implications for practice
Based on low quality evidence, the addition of interferon to first-line chemotherapy did not alter the overall survival in post-surgical women with advanced EOC compared with chemotherapy alone. There is low quality evidence to suggest that interferon in combination with chemotherapy worsened the progression free survival in post-surgical women with advanced EOC compared with chemotherapy alone. There is not enough evidence that interferon therapy alone alters overall survival or progression free survival compared to observation alone in post-surgical women who have undergone first-line chemotherapy.
Implications for research
Three of the five trials included in this review were stopped early and were, therefore, underpowered to detect any true effect of the intervention. The trials did not report the results of important outcomes in a uniform manner, preventing statistical aggregation of the results. Trial methodology was poorly reported resulting in unclear risk of bias. For clear recommendations to be made regarding the effectiveness of interferon in the treatment of advanced EOC, long-term, well conducted and adequately powered RCTs would be needed. However, the available data do not suggest that interferon has an adequately advantageous effect to warrant further investigation.
Epithelial ovarian cancer (EOC) is a life-threatening disease. Most often women become symptomatic only in the advanced stages of the disease, increasing the difficulty of treatment. Whilst the disease responds well to surgery and chemotherapy, the relapse rate is high. New treatments to prevent disease recurrence or progression, prolong survival, and increase the quality of life are needed.
To assess the effectiveness and safety of interferon after surgery in the treatment of advanced (stage II-IV) EOC.
The Cochrane Gynaecological Cancer Review Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2012, MEDLINE and EMBASE were searched to January 2012. Handsearching of conference proceedings was also undertaken. Reference lists of reviews and included trials were screened and experts in the field were contacted for additional trials. Clinical trials registers were searched for ongoing trials.
Randomised controlled trials (RCTs) involving participants with advanced EOC that compared post-operative chemotherapy alone with post-operative interferon therapy in combination with chemotherapy or post-operative chemotherapy followed by interferon or observation alone
Two review authors (AL and AM) independently screened the search results for relevant trials and extracted pre-specified information from each included trial. Data were managed using Review Manager 5.1. Hazard ratios (HR) were calculated for time-to-event outcomes and risk ratios (RR) for dichotomous outcomes, with corresponding 95% confidence intervals (CI).
Five trials, including 1476 participants, were included in the review. Two trials compared interferon with observation alone and three trials compared interferon plus chemotherapy with chemotherapy alone. A meta-analysis of two trials involving 370 participants found no significant difference in both overall survival (HR 1.14, 95% CI 0.84 to 1.55) and progression free survival (HR 0.99, 95% CI 0.79 to 1.24) between the interferon and observation alone groups in post-surgical women who had undergone first-line chemotherapy for advanced EOC. One trial with 293 participants found that while no significant difference was observed in incidence of nausea or vomiting between the two treatment groups, significantly more flu-like symptoms (RR 2.25, 95% CI 1.73 to 2.91) and fatigue (RR 1.54, 95% CI 1.27 to 1.88) were reported in the interferon group. For the second comparison, a meta-analysis of two trials comprising 244 participants found that although there was no significant difference in overall survival between the interferon plus chemotherapy and the chemotherapy alone group (HR 1.14, 95% CI 0.74 to 1.76), women in the interferon plus chemotherapy group had worse progression free survival than those in the chemotherapy alone group (HR 1.43, 95% CI 1.02 to 2.00). Compared to chemotherapy alone, adding interferon to chemotherapy did not alter the incidence of adverse events in post-surgical women with advanced EOC.