Low Doses of Eltrombopag Are Safe and Effective in the Prophylaxis of the Chemotherapy-Induced Thrombocytopenia (CIT)

Chemotherapy-induced-thrombocytopenia (CIT) can prevent the administration of the optimal dose and schedule of anticancer treatment and limit its benefits in the adjuvant or metastatic setting. Therapeutic approaches will include dose delays or reduction ,platelet transfusion and consideration of platelet-stimulating agents. In a review of chemotherapy-induced thrombocytopenia including >47 000 patients with solid tumors, CRC was associated with the highest prevalence of thrombocytopenia by cancer type, and most patients had received a platinum-based chemotherapy regimen. Experimental data demonstrated that Platinum is one of the heavy metals which may induce immune manifestations in humans and in experimental animals. However, novel mechanisms of oxaliplatin-related thrombocytopenia have been implicated and include an immune-dependent mechanism, as well as portal hypertension related to sinusoidal injury yielding splenic sequestration of platelets.

Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has been shown efficacy and safety in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy .Moreover,some clinical studies demonstrate a role for thrombopoietin agonists in improving compliance with cytotoxic regimens in cancer patients whose chemotherapy was delayed due to thrombocytopenia,[and they suggest that prophylactic use of eltrombopag or romiplostim might reduce the degree and duration of chemotherapy-induced thrombocytopenia. Here, we report on a series of 22 patients at high risk of CIT because of platinum chemotherapy schedules who received low doses eltrombopag as prophilaxis .The aim of the study was to prevent CIT in patients who cannot be supported by platelet transfusions and for whom the maintenance of dose intensity is crucial for remission or survival

Methods

A total of 22 consecutive adult patients, female (60 %), median age 47 years (range 28 - 67) were enrolled in the study. The reason of chemotherapy has been ovary cancer in 5 patients, colon cancer in 8 patients, relapsed DLBC lymhoma in 4 patients,, TNBC in 2 patients, pancreatic cancer in 3 pts. All patients received eltrombopag 25 mg by mouth twice a weekly as soon as the platelet count falls below 80000 mmc, and continued on treatment until completion of cycles of chemotherapy.

Results

The mean platelet count nadir was 60000 mmc; the number of days with platelet count < 80000/µL was 4 days; The maximum value reached was 270,000 mmc. No treatment-related toxicity was observe. 1 out of 22 pts , did not respond to the planned dose and received 50 mg for eight consecutive days before each course of chemotherapy.The principal endpoints of the study : avoid nadir platelet counts < 50,000/µL,platelet transfusions, bleeding events, chemotherapy dose reductions , chemotherapy delays. were achieved in all patients.

Conclusion

In our opinion low dose eltrombopag prophilaxis can be an effective and safe strategy for preventing the CIT.