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Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer.

Watanabe R, Takiguchi Y, Moriya T, Oda S, Kurosu K, Tanabe N, Tatsumi K, Nagao K, Kuriyama T - Br. J. Cancer (2003)

Bottom Line: Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5.Toxicity was manageable and tolerable for all.Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group.

View Article: PubMed Central - PubMed

Affiliation: Department of Respirology (B2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

ABSTRACT
Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m(-2) of cisplatin on day 1 and 50 mg m(-2) of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients.

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Time–concentration curves of platinum. After 30-min i.v. infusion of cisplatin at doses of 40 mg m−2 (n=2), 80 mg m−2 (n=5) for haemodialysis patients, or 80 mg m−2 (n=3) for patients with normal renal function, plasma concentrations of f-Pt and t-Pt were sequentially determined. Each dot and bar represent mean and standard deviation, respectively. Open and closed circles represent f-Pt and t-Pt, respectively, when 40 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed triangles represent f-Pt and t-Pt, respectively, when 80 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed squares represent f-Pt and t-Pt, respectively, when cisplatin was administered at 80 mg m−2 to patients with normal renal function. The lowest detection limit of f-Pt was 25 ng ml−1, and measurements below this value were plotted on the dotted line in this figure. Note that f-Pt levels were still detectable from days 2 to 14 in the haemodialysis patients, whereas those in patients with normal renal function were all below the detection limit at the same time points.
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fig1: Time–concentration curves of platinum. After 30-min i.v. infusion of cisplatin at doses of 40 mg m−2 (n=2), 80 mg m−2 (n=5) for haemodialysis patients, or 80 mg m−2 (n=3) for patients with normal renal function, plasma concentrations of f-Pt and t-Pt were sequentially determined. Each dot and bar represent mean and standard deviation, respectively. Open and closed circles represent f-Pt and t-Pt, respectively, when 40 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed triangles represent f-Pt and t-Pt, respectively, when 80 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed squares represent f-Pt and t-Pt, respectively, when cisplatin was administered at 80 mg m−2 to patients with normal renal function. The lowest detection limit of f-Pt was 25 ng ml−1, and measurements below this value were plotted on the dotted line in this figure. Note that f-Pt levels were still detectable from days 2 to 14 in the haemodialysis patients, whereas those in patients with normal renal function were all below the detection limit at the same time points.

Mentions: Although pharmacokinetics analysis was performed for every course of each patient and all data were monitored, only a data set from the first administration of a given dose level of an agent in each patient was analysed in this presentation to avoid a bias because of patient variation rather than dose variation. This bias would be inevitable because some patients were treated with more courses than others. Therefore, for creating the time–concentration curves in Figures 1Figure 1


Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer.

Watanabe R, Takiguchi Y, Moriya T, Oda S, Kurosu K, Tanabe N, Tatsumi K, Nagao K, Kuriyama T - Br. J. Cancer (2003)

Time–concentration curves of platinum. After 30-min i.v. infusion of cisplatin at doses of 40 mg m−2 (n=2), 80 mg m−2 (n=5) for haemodialysis patients, or 80 mg m−2 (n=3) for patients with normal renal function, plasma concentrations of f-Pt and t-Pt were sequentially determined. Each dot and bar represent mean and standard deviation, respectively. Open and closed circles represent f-Pt and t-Pt, respectively, when 40 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed triangles represent f-Pt and t-Pt, respectively, when 80 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed squares represent f-Pt and t-Pt, respectively, when cisplatin was administered at 80 mg m−2 to patients with normal renal function. The lowest detection limit of f-Pt was 25 ng ml−1, and measurements below this value were plotted on the dotted line in this figure. Note that f-Pt levels were still detectable from days 2 to 14 in the haemodialysis patients, whereas those in patients with normal renal function were all below the detection limit at the same time points.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376779&req=5

fig1: Time–concentration curves of platinum. After 30-min i.v. infusion of cisplatin at doses of 40 mg m−2 (n=2), 80 mg m−2 (n=5) for haemodialysis patients, or 80 mg m−2 (n=3) for patients with normal renal function, plasma concentrations of f-Pt and t-Pt were sequentially determined. Each dot and bar represent mean and standard deviation, respectively. Open and closed circles represent f-Pt and t-Pt, respectively, when 40 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed triangles represent f-Pt and t-Pt, respectively, when 80 mg m−2 of cisplatin was administered to haemodialysis patients. Open and closed squares represent f-Pt and t-Pt, respectively, when cisplatin was administered at 80 mg m−2 to patients with normal renal function. The lowest detection limit of f-Pt was 25 ng ml−1, and measurements below this value were plotted on the dotted line in this figure. Note that f-Pt levels were still detectable from days 2 to 14 in the haemodialysis patients, whereas those in patients with normal renal function were all below the detection limit at the same time points.
Mentions: Although pharmacokinetics analysis was performed for every course of each patient and all data were monitored, only a data set from the first administration of a given dose level of an agent in each patient was analysed in this presentation to avoid a bias because of patient variation rather than dose variation. This bias would be inevitable because some patients were treated with more courses than others. Therefore, for creating the time–concentration curves in Figures 1Figure 1

Bottom Line: Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5.Toxicity was manageable and tolerable for all.Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group.

View Article: PubMed Central - PubMed

Affiliation: Department of Respirology (B2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

ABSTRACT
Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m(-2) of cisplatin on day 1 and 50 mg m(-2) of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients.

Show MeSH
Related in: MedlinePlus