Phase II trial of two different irinotecan schedules with pharmacokinetic analysis in patients with recurrent glioma

27 October 2008

Santisteban M, Buckner JC, Reid JM, Wu W, Scheithauer BW, Ames MM, Felten SJ, Nikcevich DA, Wiesenfeld M, Jaeckle KA, Galanis E.

Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA.

Purpose The aims of this trial were to assess the safety and efficacy of two different dosing schedules of irinotecan (CPT-11) in recurrent glioma patients, to assess irinotecan pharmacokinetics in patients on enzyme-inducing antiepileptic drugs (EIAEDs) and steroids, and to correlate with toxicity and response to treatment. Methods Sixty-four recurrent glioma patients were included in this study. Schedule A patients received irinotecan weekly (125 mg/m(2)/w) for four out of six weeks. Schedule B patients received irinotecan every three weeks at a dose of 300 mg/m(2). A 20% dose reduction was implemented for patients who had received prior nitrosureas. Treatment was continued until unacceptable toxicity, tumor progression or patient withdrawal. Results There was no difference in confirmed responses between the two groups (6.3%). PFS at 6 months was 6.25% (2/32 patients) on schedule A and 18.75% (6/32 patients) on schedule B but median OS (5.1 versus 5.5 months), and survival at one year (19%) was similar for both arms. The most common grade 3-4 toxicities on schedules A/B were: thrombocytopenia (15.6%/21.9%), diarrhea (6.3%/12.5%) and nausea and vomiting (0%/15.7%). One toxic death due to infection in the absence of neutropenia occurred in schedule B. EIAEDs reduced SN-38 and CPT-11 area under the curve and increased CPT-11 cleareance. This effect was more prominent in schedule A patients. Steroids did not alter CPT-11 pharmacokinetics in either schedule. Conclusions Single agent irinotecan has modest activity in patients with recurrent gliomas, independently of the administration schedule. Irinotecan administration on an every 3 week schedule resulted in longer PFS-6, at the expense of more toxicity. EIAEDs alter CPT-11 pharmacokinetics in this group of patients, and should be taken into consideration when determining optimal dosing.

PMID: 19066728 [PubMed - as supplied by publisher]

Commento Personale: L'irinotecan come agente singolo, ma direi anche come agente in combinazione con l'Avastin, risulta essere praticamente inutile. I suoi risultati sono spesso inferiori anche all'utilizzo delle vecchie nitrosuree.

Source J Neurooncol. 2008 Dec 10