Effectiveness and safety of recombinant human thrombopoietin on treating chemotherapy-induced thrombocytopenia: Data pool analysis of phase II/III and complement multi-center clinical trials

Objective: To assess the effectiveness and safety of recombinant human thrombopoietin(rh-TPO) on chemotherapy-induced thrombocytopenia(CIT) in patients with solid tumor. Methods: A total of 276 cases were enrolled in 3 studies, 63 cases in Phase II study, 154 cases in Phase HI study and 59 cases in complement study. A total of 230 cases were enrolled pre-protocol (PP) group, except of 5 protocol deviations, 41 lost-follow-ups. All of the patients had solid tumor which was confirmed by histology or cytology. Phase II and complement trials were randomized crossover self-control trials. It was divided into randomized-crossover-self-control part and non-randomized-crossover-self-control part in Phase HI trial depending on if the subject was joined by randomized-crossover. The period when rh-TP subject was administered was defined as an administration period, and the other period was defined as a control period. The chemical therapeutic regimen and dosage did not change during the trials. All of the trials data were pooled together to compare the efficacy and safety profile. Results: They showed the utilized changes both in intention-to-treat (ITT) group and PP group when compared with the treated cycle and control cycle (following example with ITT group data). Compared with the control period, rh-TPO could significantly decrease the degree of CIT (minimal mean platelet count: (L 63. 02± 46. 48 J X 10⁹ vs [49.47 ±31.41]×l07L, P= 0.002); shorten the thrombocytopenia duration induced by chemotherapy(days of platelet count recovered to 75 × 10 /L:| 11. 18 ±9.71 J as | 17.8 ±10. 46 J d, P = 0. 000); and highly increase recover level of platelet count (platelet count of last visit: [211.21 ± 119.20] × lO vs [138. 13 ±71.54] × lO'/L, P= 0.000; maximal mean platelet count: [262. 78 ± 162. 60] × lO vs [149. 36 ± 73. 26] × lO'/L, P = 0. 000; platelet count' s difference between the last visit and baseline: [79. 64 ± 118. 06] vs [- 8. 92 ± 102. 50], P =0. 000). On the other hand, rh-TPO could decrease the ratio of patients who had to be transfused with platelet (12.21%vs19.85%, P = 0. 017); and decrease the time ([0. 22 ± 0. 72] vs [0. 37 ± 0. 90] time, P - 0. 010) and the quantity ([1. 66 ± 6. 09] vs [2. 77 ±7. 08 J U, P =0. 009) of platelet transfusion. It was much more significantly in the complement trial (13. 79% vs 33. 93%, P =0. 0082). There were no significant differences before and after treatment on Hb, WBC, liver and renal function and blood coagulation (P> 0. 05). There were only 11 cases who met side effects during the studies, most of whom presented fever (6 cases) and chill (2 cases). Conclusion: Administration of rh-TPO after chemotherapycan may significantly reduce the degree and duration of thrombocytopenia induced by chemotherapy and promote platelet recovery of patients with solid tumors. It also decreased the capability of platelet transfusion, and severe side effects were not found.