Elsevier

Bulletin du Cancer

Volume 99, Issue 4, April 2012, Pages E43-E48
Bulletin du Cancer

Routine administration of a single dose of cisplatin  75 mg/m2 after short hydration in an outpatient lung-cancer clinic

https://doi.org/10.1684/bdc.2012.1555Get rights and content

Abstract

Background

Cisplatin is a pivotal drug in combined chemotherapy for non-small cell and small-cell lung cancers (NSCLC or SCLC), but its renal toxicity limits its use. Current guidelines recommend 24 h hydration: thus hospitalization is required. The aim of this retrospective study was to confirm the safety of short hydration before giving an intermediate-to-high dose of cisplatin in an outpatient clinic.

Patients and methods

Patients eligible had NSCLC or SCLC and were being treated with a chemotherapy regimen that included cisplatin  75 mg/m2. They were given the same short hydration protocol for 1 day. Nephrotoxicity was defined as  grade 1 according to NCIC common toxicity criteria. Predictive factors for nephrotoxicity were analyzed.

Results

Three hundred and fifty-seven consecutive patients (median age 58 years, range: 25-81) were reviewed. Twenty-one patients (6%) had  grade 1 nephrotoxicity and all except one had grade 1 toxicity according to NCIC criteria for common toxicity (SC < 1,5 N). Predictive factors independently associated with nephrotoxicity included associated co-morbid conditions (hypertension, diabetes, heart disease) (OR = 4.97 CI 95% [1.8-13.7] P = 0.002), initial serum creatinine  100 μmol/L (OR = 8.3 CI 95% [2.55-27.4] P = 0.0005), and dose cycle of cisplatin  100 mg/m2 (OR = 10.8 CI 95% [3.6-32.5] P < 0.0001).

Conclusion

Rapid outpatient administration of a single dose of cisplatin at  75 mg/m2 is feasible without a high risk of nephrotoxicity.

Introduction

A cisplatin-based combination therapy is currently considered the most active treatment option for several types of solid tumors, including lung cancer. In phase III trials, the association of cisplatin with one of the third-generation agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, or pemetrexed [restricted to non-squamous histologies for the latter]) has demonstrated efficacy in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC) [1., 2., 3., 4.]. Moreover, cisplatin-based chemotherapy also significantly increased overall survival rates of patients with completely resected NSCLC [5., 6., 7.]. Thus, a large proportion of patients with NSCLC are being treated with cisplatin-based chemotherapy. When cisplatin was first approved for commercial use in 1978, major causes of toxicity included severe nausea and vomiting and a high incidence of renal dysfunction. These adverse effects were reduced by the use of 5HT3-receptor antagonists and hydration [8].

Most instructions concerning hydration recommend the use of a pre-treatment regimen with 1 to 2 L of fluid infused for 8 to 12 h, with the drug diluted in 2 L of 5% dextrose, in half or one third normal saline containing 37.5 g of mannitol, and infused over a 6- to 8-h period (US Food, BC Cancer Agency). It is also recommended that hydration and control of diuresis are maintained during the following 24 h, eventually with a diuretic. Nevertheless, no consistent data exist concerning the specific protective effect of either mannitol or furosemide, or the duration of hydration [8, 9]. Ambulatory oncological care has been widely developed to reduce time spent in the hospital unit, one of the most important concerns for cancer patients [10, 11]. In addition, the safety of cisplatin administration to outpatients has been queried. Moreover, conventional cisplatin administration usually requires complete hospitalization in most countries. Therefore, we carried out retrospective evaluation of the safety and tolerance of treating outpatients with cisplatin between 2001 and 2007. Nephrotoxicity was considered in this report as the primary criterion for safety analysis, and the toxicity scale of NCI was based on creatinine level, as this is used in all therapeutic trials and reflects our daily oncological routine.

Section snippets

Selection of patients

Patients eligible for the retrospective study (between January 2001 and May 2007) had NSCLC or small-cell lung cancer (SCLC) and were treated at the outpatient clinic of Tenon University Hospital with a chemotherapy regimen that included cisplatin  75 mg/m2 with a pre-planned short hydration protocol delivered intravenously in 2 h. Patients who were consecutively treated with fractionated cisplatin  75 mg/m2 were excluded. Study parameters included age, gender, and weight before and after each

Patients

The data from 357 consecutive patients with NSCLC or SCLC were analyzed. The patients’ characteristics are shown in table 1 . Among the 357 patients, 250 were men. The median age was 58 years (range: 25-81 years) and 7% were aged > 70 years. The ECOG PS was 0 in 80% of cases, 1 in 19% of cases, and 2 in 1% of cases. The subtype histology was NSCLC in 340 patients (adenocarcinoma: 47%, squamous cell: 27%, large cell: 10%, and others: 16%), and SCLC in 17 patients. For NSCLC, disease stage was I-II in

Discussion

Among the 357 patients evaluated in this study, only 21 (6%) had nephrotoxicity grade  1 according to NCIC criteria. Among these 21 patients, toxicity was minor (grade 1, 1N < SC  1.5N) in 20 patients (95% of cases). Moreover, nephrotoxicity returned to grade 0 after completion of treatment in 12 patients out of 20 (data not shown). Only one patient had nephrotoxicity grade 3, which returned to grade 2 after completion of treatment. We selected the NCIC criteria as the definition for nephrotoxicity

Conflict of interest

none.

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