Cisplatin Pharmacokinetics in Elderly Patients

Bonetti, A; Franceschi, T.; Apostoli, P; Cetto, Gian Luigi; Recaldin, E; Molino, Annamaria; Leone, Robert D.

doi:10.1097/00007691-199410000-00006

Cited by 27 publications

(8 citation statements)

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“…Pharmacokinetic studies of chemotherapy drugs in older patients have revealed a delayed clearance of drugs used in testicular cancer [15], and increased toxicity for an equivalent drug exposure [16]. In particular, renal function is known to decline with age [17], and serum creatinine may be an insufficient indicator of glomerular filtration in the older patient.…”

Section: Discussionmentioning

confidence: 99%

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

Wheater¹,

Manners²,

Nolan³

et al. 2011

BJU International

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Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject ? and What does the study add? The treatment of younger men with testicular germ cell cancers is well documented with established intensive chemotherapy regimens for those with advanced disease. Although the majority of patients present in the third or fourth decade, men also present in later life. These patients are typically excluded from clinical trials and there are no contemporary published series describing their management. This series describes the management of older patients with testicular germ cell tumours at both early and advanced stages of disease. Patients with stage I seminoma can be safely managed with all recognised treatment strategies and state I non‐seminomas were managed with surveillance. Cure can still be achieved in older patients with advance germ cell tumours however chemotherapy regimens developed in younger patients must be tailored to the presence of co‐morbidity. OBJECTIVES • To review the practice of a large referral centre for the management of older patients with testicular germ cell cancer (GCC). • There are few published data available on the management of testicular GCC in elderly patients, who often have medical comorbidities and have been excluded from clinical trials. PATIENTS AND METHODS • We reviewed our prospectively collected database for patients presenting with GCC who were aged ≥60 years. • Details of presentation, management and outcome were recorded. RESULTS • In total, 60 patients aged ≥60 years were identified from 1461 patients treated with GCC from 1979–2005, representing 4% of the total population. • Median age was 67 years, 44 had seminoma (73%) and 16 had non‐seminoma histology (27%). • Stage I seminoma patients were managed with surveillance, adjuvant radiotherapy and adjuvant carboplatin. All stage I non‐seminomas underwent surveillance. • In total, 15 patients received systemic chemotherapy for metastatic disease with modified bleomycin, etoposide and cisplatin; etoposide and cisplatin; carboplatin‐based regimens; or other combinations. Toxicity was manageable, with no toxic deaths. • In total, four patients (6.7%) died of GCC. CONCLUSIONS • In elderly patients, GCC should be managed with curative intent. • Conventional therapies are tolerable for most men with stage I seminoma. In metastatic disease, comorbidity may necessitate treatment modifications. • Most patients are cured with manageable toxicity.

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Section: Discussionmentioning

confidence: 99%

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

Wheater¹,

Manners²,

Nolan³

et al. 2011

BJU International

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“…In addition, eorts should be made to further analyze the in¯uence of the patients' age on the pharmacokinetics of carboplatin. Age has been described as in¯u-encing the pharmacokinetics of cisplatin (Bonetti et al 1994;Yamamoto et al 1995), while corresponding data on carboplatin are limited. Therefore, in the case of con®rmation of the current results, the patients' age should be included in calculation formulas for the carboplatin dose.…”

Section: Discussionmentioning

confidence: 99%

Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve

Kern

Braess

Friedrichsen

et al. 2001

Journal of Cancer Research and Clinical Oncology

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“…The toxic and therapeutic effects of both etoposide [4] and the platinum complexes [5] are related to the plasma drug concentrations achieved in individual patients. Therapeutic drug monitoring to achieve or maintain target plasma drug concentrations has been employed for etoposide [4, 6, 7] and carboplatin [8], and has been suggested for cisplatin [9] in an attempt to optimize drug exposure in each individual patient. The plasma concentration profile of any drug is determined by the balance between the dose administered and the rate of elimination.…”

Section: Introductionmentioning

confidence: 99%

Randomized cross‐over clinical trial to study potential pharmacokinetic interactions between cisplatin or carboplatin and etoposide

Thomas

Porter

Bartelink

et al. 2002

Brit J Clinical Pharma

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Aims Cisplatin and carboplatin are often used in combination with etoposide. In a randomized cross-over study, the potential interaction between the two platinum drugs and the metabolism of etoposide was explored. In vitro investigations using human liver microsomes were also performed. Methods Etoposide was administered to 15 patients over 3 days, with the platinum drug administered on day 2. The alternate platinum drug was administered on the second course. The pharmacokinetics of etoposide were determined on all 3 days of each cycle. The effect of platinum drugs on etoposide metabolism by human liver enzymes was explored in vitro. Results Neither cisplatin nor carboplatin coadministration affected the pharmacokinetics of etoposide during cycle 1. When carboplatin was administered on course 2, etoposide AUC was 8% higher on day 2 compared with day 1 or day 3 (for day 2 vs day 3, 95% CI: x0.72, x0.08 mg ml x1 min). In contrast, cisplatin on course 2 increased the AUC of etoposide (28%) on day 3 (day 3 vs day 1, 95% CI: 0.67, 2.09 mg ml x1 min), with no effect on day 2. In vitro carboplatin and cisplatin (10±100 mM) inhibited the metabolism of etoposide, if rat liver microsomes were preincubated (30 min) with NADPH and the platinum complexes. With human liver microsomes a small effect on etoposide metabolism, but not on catechol formation, was observed. Conclusions The interaction between etoposide and platinum drugs is small and, given the pharmacokinetic variability seen with etoposide, the clinical impact is unlikely to be signi®cant.

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Cisplatin Pharmacokinetics in Elderly Patients

Cited by 27 publications

References 0 publications

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve

Randomized cross‐over clinical trial to study potential pharmacokinetic interactions between cisplatin or carboplatin and etoposide

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