Renal Tolerance to Cisplatin in Patients 70 Years and Older

Abstract

The purpose of this study was to evaluate cisplatin nephrotoxicity in patients 70 years and older and to identify factors influencing nephrotoxicity occurrence. Forty-nine (N = 49) patients older than 70 years were studied retrospectively. All patients received treatment with cisplatin. Variables under study were as follows: prechemotherapy serum creatinine levels (Crb), maximum serum creatinine level during treatment (Crmax), steady serum creatinine level 3 months after treatment completion (Crstb), as well as their corresponding creatinine clearance values (CrbC, CrmaxC, CrstbC) as calculated by the Cockroft and Gault formula. Maximum creatinine increment (Imax = Crmax - Crb), stable creatinine increment (Istb = Crstb - Crb) and the corresponding clearance decrements (Dmax and Dstb) were calculated as well. The potential relationship of the above variables to cisplatin dose intensity and accumulated dose as well as to different prognostic factors were also considered. Assessment of associated conditions was carried out by means of Charlson comorbidity index. The patients' mean age was 73 years (range: 70-79 years). There were 43 men (88%) and 6 women (12%). Mean cisplatin dose intensity was 27 mg/m2/wk. A total of 157 chemotherapy courses were administered with a mean of 3.2 per patient. Mean Crb was 1.02 mg/dl (95% CI = 1.02-1.12), mean Crmax was 1.45 (95% CI = 1.34-1.46), and mean Crstb was 1.24 (95% CI = 1.16-1.32). Imax was equal to 0 in 13 patients (26%) and more than 0.4 mg/dl in 21 patients (43%). Istb was equal to 0 or negative in 22 (45%) and more than 0.4 in only 9 patients (18.3%). No significant relationship of serum creatinine levels, creatinine clearance levels, or of their increments or decrements to cisplatin dose intensity or accumulated dose were found. These levels also did not correlate with age, sex, comorbidity or Eastern Cooperative Oncology Group score. In 85% of patients, Crmax was reached between chemotherapy initiation and the third chemotherapy course, and thereafter renal function began to recover despite continued administration of cisplatin. Cisplatin is well tolerated by patients 70 years and older and dose intensity does not seem to influence renal function deterioration. Therefore, we failed to find reasons to encourage modification or limitation of cisplatin treatment in the elderly population.

Safety profile of platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer in elderly patients

“…However, several retrospective subset analyses of platinum-based chemotherapy trials have demonstrated no, or minimal, differences between elderly patients who met the stringent eligibility criteria of the clinical trials and younger patients treated with platinum-based therapies. The results of subset analyses, however, should be interpreted with care due to the potential risk of selection bias [27,[95][96][97][98][99][100][101][102][103].…”

“…A retrospective analysis of cisplatin-based chemotherapy in NSCLC patients revealed a significant increase in death rates within 30 days of starting chemotherapy with increasing age (0.5, 3.3, 3.2, 7.1 and 12.5% for ≤ 54, 55 -59, 60 -64, 65 -69 and ≥ 70 years; p = 0.0001) [91]. However, the frequency of renal toxicity after cisplatin administration to elderly patients has been studied by several authors and, with the exception of one trial [92], the studies demonstrated an acceptable rate of renal function deterioration, without a significant increase in age-related incidence [93][94][95].…”

Experimental verification of age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography

“…2 Cubillo et al reported that cisplatin was found to be well tolerated by patients ≥70 years, suggesting that age does not infl uence renal function deterioration. 3 However, several studies on cisplatin in the elderly have yielded confl icting results. 4,5 Mollman et al advocated cisplatin treatment interruption in the elderly if paresthesias appear after cumulative doses of <300 mg/ m 2 .…”

Fractionated dose of cisplatin (CDDP) and vinorelbine (VNB) chemotherapy for elderly patients with advanced non-small cell lung cancer: Phase II trial

“…Many therapeutic approaches have been developed in order to treat this particular category of patients, the great majority of them being focused on the use of a single agent or a combination of new drugs [10][11][12][13][14][15].…”