Thrombopoietin receptor agonists for prevention and treatment of chemotherapy-induced thrombocytopenia in patients with solid tumours.

backgroundChemotherapy-induced thrombocytopenia (CIT) is defined as a peripheral platelet count less than 100×10

objectivesTo assess the effects of TPO-RAs to prevent and treat CIT in patients with solid tumours:(1) to prevent CIT in patients without thrombocytopenia before chemotherapy, (2) to prevent recurrence of CIT, and (3) to treat CIT in patients with thrombocytopenia during chemotherapy. SEARCH

methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, to 28 September 2017), MEDLINE (from 1950 to 28 September 2017), as well as online registers of ongoing trials (Clinical Trials, Chinese Clinical Trial Register, Australian New Zealand Clinical Trial Registry, WHO ICTRP Search Portal, International Standard Randomised Controlled Trial Number registry, GlaxoSmithKline Clinical Study Register, and Amgen Clinical Trials) and conference proceedings (American Society of Hematology, American Society of Clinical Oncology, European Hematology Association, European Society of Medical Oncology, and Conference Proceedings Citation Index-Science, from 2002 up to September 2017) for studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing TPO-RAs alone, or in combination with other drugs, to placebo, no treatment, other drugs, or another TPO-RAs for CIT in patients with solid tumours. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard methodological methods expected by Cochrane. MAIN

resultsWe identified six trials eligible for inclusion, of which two are ongoing, and one awaiting classification study. The three included trials were conducted at many different sites in Europe, America, and Asia. All of the three studies recruited adult and elder participants (no children were included) with solid tumours, and compared TPO-RAs with placebo. No studies compared TPO-RAs alone, or in combination with other drugs, to no treatment, or other drugs, or another TPO-RAs.We judged the overall risk of bias as high as we found a high risk for detection bias. We assessed the risk of bias arising from inadequate blinding of outcome assessors as high for number and severity of bleeding episodes (one of the primary outcomes).To prevent CIT: We included two trials (206 participants) comparing TPO-RAs (eltrombopag, multiple-dose oral administration with chemotherapy) with placebo. The use of TPO-RAs may make little or no difference to the all-cause mortality at 33 weeks of follow-up (RR 1.35, 95% CI 0.53 to 3.45; one trial, 26 participants; low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 0.62, 95% CI 0.22 to 1.78; two trials, 206 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (RR 0.36, 95% CI 0.06 to 2.06; two trials, 206 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life.To prevent recurrence of CIT: We included one trial (62 participants) comparing TPO-RAs (romiplostim, single-dose subcutaneous administration with chemotherapy) with placebo. There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 2.80, 95% CI 0.17 to 47.53; one trial, 62 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (no severe/life-threatening bleeding episodes; one trial, 62 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), it is planned to give TPO-RAs (romiplostim, subcutaneous administration with chemotherapy) to participants, but to date this trial has not reported any outcomes.To treat CIT: We found one ongoing study (expected recruitment 83 participants), which is planned to give TPO-RAs (eltrombopag, seven days orally) to participants when their platelet counts are less than 75×10 AUTHORS'

conclusionsNo certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. There was no evidence to support the use of TPO-RAs for treating CIT in patients with solid tumours.