Topotecan is an active second line chemotherapeutic drug, used to treat patients with relapsed ovarian carcinoma

Ovarian cancer is one of the most common malignancies of the female genital tract which accounts for approximately 3% of all cancer in women, and is the leading cause of death from gynecological cancer in developed country. Appropriate initial surgical management by a gynaecologic oncologist is important for survival. Patients with early stage, low-risk tumours may be cured with surgery alone. Current first-line management for advanced ovarian cancer consists of cytoreductive surgery followed by chemotherapy. The majority of patients relapse between 18 to 22 months later. Management of recurrent ovarian cancer remains a challenge. Goals for treating relapsed ovarian cancer include improving symptoms, enhancing quality of life (QOL), and prolonging survival. Agents that are potentially well suited for extended treatment intervals may include such properties as absence of cumulative toxicity, non cross resistance, positive benefit on QOL, and convenient schedule. Of the agents available for the treatment of relapsed ovarian carcinoma, topotecan is one of the most widely studied and characterised. This review aims to evaluate the efficacy and safety of topotecan in the management of ovarian cancer.

Six multicentre, well designed pre-market studies including 5640 participants were eligible for this review. Pooling analysis did not performed in four trials due to the data not similar enough, but conducted for two trials. Topotecan appears to have a similar level of effectiveness as paclitaxel, topotecan plus thalidomide, and superior than treosulfan, but shorter overall survival than pegylated liposomal doxorubicin. Topotecan delays progression of disease than paclitaxel, treosulfan; topotecan plus thalidomide superior than topotecan alone on PFS, but topotecan alone significantly shorter than topotecan plus thalidomide. Further consolidation treatment with topotecan does not improve PFS for participants with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

Evidence from three studies were high quality, remain four studies were low or moderate due to poor reporting of the methodology. For gaining the better representativeness, more large, well-designed randomised controlled trials of post-market drug are required in the future.

Authors' conclusions: 

Topotecan appears to have a similar level of effectiveness as paclitaxel, topotecan plus thalidomide, but shorter overall survival than PLD in the platinum-sensitive participants; adelays progression of disease than paclitaxel, treosulfan; topotecan plus thalidomide superior than topotecan alone on PFS. After received carboplatin and paclitaxel, further treatment by topotecan not appeared benefit than no further treatment for ovarian cancer on overall survival and progression-free survival. Topotecan may has different patterns of side effects. The quality of evidence from these studies ranged from low to moderate. More large, well-designed and good conducted and good reported, particularly post-market studies are still required in the future in order to conform the effect and safety, and to have better representativeness.

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Background: 

Chemotherapeutic agents such as topotecan can be used as salvage treatment in epithelial ovarian carcinoma (EOC). The effects of using topotecan as a therapeutic agent have not been previously been systematically reviewed.

Objectives: 

To evaluate the effectiveness and safety of topotecan for the treatment of ovarian cancer.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 6, 2015); Cochrane Gynaecological Cancer Review Group (CGCRG) Specialised Register (Cochrane Library Issue 6, 2015); MEDLINE (January 1990 to 30 September 2015); EMBASE (January 1990 to 30 September 2015); The European Organization for the Research and Treatment of Cancer (EORTC) database (to 30 September 2015); CBM (Chinese Biomedical Database) (January 1990 to 30 September 2015).

Selection criteria: 

Randomised controlled trials (RCTs) which randomise participants with ovarian cancer to single or combined use of topotecan versus interventions without topotecan.

Data collection and analysis: 

Two review authors independently extracted and analysed data.

Main results: 

Six multicentre, well designed studies including 5640 participants were eligible for this review. Pooling analysis did not performed due to the data not similar enough. Two studies included primary EOC participants, remain four included recurrent EOC participants. In primary EOC participants, topotecan did not show benefit on overall survival (OS) (HR 1.051, 95%CI 0.925 to 1.194, and HR 1.051, 95% CI 0.93 to 1.19, respectively) and progression-free survival (PFS)(HR 1.066, 95%CI 0.958 to 1.186, and HR 1.18, 95%CI 0.86- 1.63, respectively). The median overall survival of participants treated by topotecan were 39.6 to 63 weeks, no significant difference was found in comparing with no further cytotoxic or noncytotoxic treatment (P = 0.30), pegylated liposomal doxorubicin (PLD)(P=0.341), paclitaxel (P=0.44), topotecan plus thalidomide (P=0.67), respectively; but significantly superior than treosulfan (P = 0.0023). in the platinum-sensitive participants group, overall survival (OS) favoured PLD over Topotecan (HR = 1.23, 95% CI 1.01 to 1.05). The greatest effect was seen in the partially platinum sensitive subgroup where HR was 1.58 (1.071-2.335).

To comparable effectiveness to prolong progression-free survival (PFS), topotecan was 16 to 23 weeks, no statistical significant difference existed in the comparing with PLD (P= 0.095), and no further cytotoxic or noncytotoxic treatment (P=0.31, HR 1.07; 95% CI 0.94 to 1.23); Topotecan showed significantly delayed the progression campared with treosulfan (23.1 weeks versus 12.7 weeks, P = 0.0020), but no significant difference with paclitaxel (18.9 weeks versus 14.7 weeks, P=0.076); on the PFS, topotecan significantly shorter than topotecan plus thalidomide (4 months versus 6 months, P = 0.02).

Topotecan was more hematologically toxic compared with paclitaxel, PLD, treosulfan, relative risks (RRs) of hematological events ranged from 1.03 to 14.46 and 1.73 to 27.12, or incidence were 50% versus 12.2%, respectively. Small tumour diameter, sensitivity to platinum-based chemotherapy was associated with better prognosis.

Three studies with lower risk of bias, remain four studies unclear due to poor reporting of the methodology. The evidence quality ranged from low to high,

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