The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.

Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered.

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Letrozole (trademark Femara) is a new orally active, potent and selective aromatase inhibitor for the hormonal treatment of advanced breast cancer in postmenopausal women. The pharmacokinetics of letrozole and the suppression of peripheral estrogens were studied in 28 breast cancer patients after a single dose and at steady state. The pharmacokinetics of two distinct age groups (> or =50, < or =65, N=15 and > or =70 years old, N=9) were compared. There were no significant differences in area under the curve (AUC) or terminal half-life between the two age groups neither after a single dose nor at steady state. However, when comparing steady state to single dose kinetics, half-life and AUC increased significantly by 42% (90% CI: 1.13, 1.78) and 28% (90% CI: 1.12, 1.47), respectively. This deviation from linearity was probably due to a partial saturation or auto-inhibition of the dominant metabolic clearance mechanism of letrozole. At steady state, approximately 70% of the administered dose was excreted in urine as unchanged letrozole (6.0+/-3.8%) or as the glucuronide of the major, pharmacologically inactive metabolite CGP44645 (64.2+/-22.7%). A single dose of letrozole caused suppression of serum estrogen levels close to the quantification limit of the assay. No difference between single dose suppression and suppression at steady state could be detected.

Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of taxane-induced toxicity. We studied 95 patients affected by breast cancer and under treatment with taxanes as adjuvant, metastatic or neo-adjuvant therapy. We genotyped them for SNPs in the CYP2C8 (alleles *1, *2, *3 and *4), CYP1B1 (alleles *1 and *3) and ABCB1 (1236 C>T; 2677 G>T/A; 3435 C>T) genes by real-time PCR assay. We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-taxane adduct and possibly inhibit taxane toxicity. We suggest that CYP1B1 might affect taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.

Prognostic factors in transitional cell carcinoma of the upper urinary tract were assessed with histopathological examination and flow cytometric analysis in a series of 127 patients operated upon between 1976 and 1988. In particular, we evaluated the usefulness of flow cytometry to identify patients who require adjuvant treatment among those with low grade and low stage disease (51% in this series). A multivariate analysis was done on 92 cases, considering patient age and sex, stage, grade and number of lesions (unifocal versus multifocal), site (renal pelvis versus ureter), presence of vesical tumors, recurrences along the urinary tract or in the bladder, type of operation and nuclear deoxyribonucleic acid (DNA) ploidy (diploid versus tetraploid/aneuploid tumors). Only the stage (p = 0.001), grade (p = 0.001) and, to a lesser extent, the DNA pattern (p = 0.031), as well as the number of lesions (p = 0.061) were determinant for prognosis. In regard to the subgroup of 41 patients with grade 2 or less, stage P1 or less tumors, no significant difference in survival was demonstrated between diploid and nondiploid tumor patients. However, 7 of 10 patients from the latter group are still under observation. Therefore, our conclusions may have to be modified in the future.

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