Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy.

In view of the similarity in chemical structure of the available 5HT(3)-receptor antagonists it is assumed, whilst these agents all act at the same receptor, that failure to one agent would predict subsequent failure to all 5HT(3)-receptor antagonists. We conducted a randomized double blind trial of granisetron 3 mg plus dexamethasone 10 mg versus continued treatment with ondansetron 8 mg plus dexamethasone 10 mg in patients with protection failure on ondansetron 8 mg plus dexamethasone 10 mg during the first 24 hours following highly emetogenic chemotherapy. Of 40 eligible patients, 21 received ondansetron + dexamethasone and 19 received granisetron + dexamethasone.

Does P-glycoprotein play a role in anticancer drug pharmacokinetics?

The multidrug-resistance P-glycoprotein is a drug efflux transport protein abundantly present in various types of human cancer. The protein is encoded by the MDR1 gene and its function is sensitive to modulation by competitive inhibition. Clinical studies have indicated that inhibitors of P-glycoprotein function dramatically decrease the systemic clearance of anticancer agents, necessitating dose reduction.

Factors involved in prolongation of the terminal disposition phase of SN-38: clinical and experimental studies.

The active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxycamptothecin (SN-38), is either formed through enzymatic cleavage of CPT-11 by carboxyl esterases (CEs) or through cytochrome P-450 3A-mediated oxidation to 7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin (NPC) and a subsequent conversion by CE. In the liver, SN-38 is glucuronidated (SN-38G) by UGT1A1, which also conjugates bilirubin. Fourteen patients were treated with 350 mg/m2 CPT-11, and we performed pharmacokinetic analysis during a 500-h collection period.

Treatment of disseminated non-seminomatous testicular cancer: the European experience.

The majority of patients with disseminated germ cell cancer can be cured with cisplatin-based combination chemotherapy. For more than a decade the gold standard regimen is cisplatin, etoposide, and bleomycin (BEP). On both sides of the Atlantic, a number of studies have been carried out to either modify the toxicity of therapy in good prognosis patients or to improve the treatment outcome by intensifying the regimen or incorporating new agents in patients with intermediate or poor prognosis disease.

A phase I/II study of multicyclic dose-intensive chemotherapy supported with G-CSF, or G-CSF and haematopoietic progenitor cells in whole blood, in two consecutive cohorts of patients.

We investigated the reconstitutive potential of haematopoietic progenitor cells collected in autologous whole blood during multicycle dose-intensified chemotherapy. Forty patients with metastatic solid tumours were treated with up to six cycles of cisplatin and escalating doses of ifosfamide every 14 days. Cisplatin was administered in 3% sodium chloride over 3 h, followed by ifosfamide over 24 h and mesna over 36 h.