Adjustment of creatinine (Cr) to avoid severe thrombocytopenia of carboplatin (C) plus gemcitabine (G) in non-small cell lung cancer (NSCLC)

Abstract

2525 Background: Carboplatin plus gemcitabine (CG) is a standard regimen for advanced NSCLC. Although the dose of C is calculated from Cr clearance (CCr) by Calvert‘s formula, severe thrombocytopenia sometimes occurs in the CG regimen. Severe thrombocytopenia might arise from differences in the methods of measuring Cr values. We have used two different techniques, the Jaffé method and the enzymatic method. When the enzymatic method was used, CCr overestimated the glomerular filtration rate and the dose of C calculated by Calvert‘s formula leads to overdosing. The aim of this study was to clarify whether severe thrombocytopenia could be avoided by adjusting the CCr in the CG regimen when Cr is measured by the enzymatic method. Methods: All patients (pts) were treated with CG (C, AUC = 5 on day 1; G, 1,000 mg/m2 on days 1 and 8) every 3 weeks for 4 cycles. Serum Cr values were measured by the enzymatic method and CCr was estimated by the Cockcroft-Gault formula in all patients. In the non-adjusted group, the dose of C was calculated by Calvert‘s formula with no adjustment of CCr. In the adjusted group, the dose of C was calculated by Calvert‘s formula, adjusting Cr as follows: (serum Cr +0.2). We compared the correlations between Cr values and the nadir of thrombocytes, and the frequencies of severe thrombocytopenia in both groups. Results: 32 pts and 28 pts were enrolled in the non-adjusted and the adjusted groups, respectively. Grade 3/4 thrombocytopenia was observed in 19 pts (60%) and these pts had low levels of serum Cr values. On the other hand, significantly fewer cases of grade 3/4 thrombocytopenia were observed in the adjusted group (8 pts; 29%, p < 0.0001). In addition, there was a significant correlation between Cr values and the nadir of thrombocytes in the non-adjusted group (R= 0.442, p= 0.0105), but no significant correlation was observed in the adjusted group (R= -0.196, p= 0.3212). These results suggest that adjustment of CCr can reduce the variable nadir of thrombocytes in the CG regimen when Cr is measured by the enzymatic method. Conclusions: If Cr is measured by the enzymatic method, adjustment of Cr is needed to avoid severe thrombocytopenia in the CG regimen. No significant financial relationships to disclose.