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There has recently been a marked trend to increasing dose intensity in cancer chemotherapy, with or without peripheral blood stem-cell support, which has been associated with a higher frequency of nausea and vomiting. Antiemetic treatment in this setting has not been extensively analysed. From October 1995 to January 1997, prevention of emesis with granisetron 3 mg/12 h i.v., dexamethasone 12 mg/24 h i.v., haloperidol 0.5 mg/12 h p.o., and loracepam I mg/24 h p.o. was instituted in 30 breast cancer patients treated with high-dose chemotherapy (a 4-day intravenous continuous infusion of cyclophosphamide 1500 mg/m2 per day, thio-TEPA 125 mg/m2 per day and carboplatin 200 mg/m2 per day).A total of 30% of the patients (9/30) obtained complete or major protection on the 4 days of chemotherapy treatment (96.7% (29/30) on day 1, 86.7% (26/30) on day 2, 70% (21/30) on day 3, and 50% (15/30) on day 4). On the days following chemotherapy, 46.7% (14/30) presented fewer than two emetic episodes on day 5, 70% (21/30) on day 6, 83.4% (25/30) on day 7 and, 93.3% (28/30) on day 8. This energic antiemetic combination treatment has hardly any effect in the prevention of emesis, providing complete or major protection of 30% for the 4 days of chemotherapy treatment. Further investigation aimed at improving antiemetic treatment results is necessary.

Mitonafide was the first synthetized compound of a new series of 3-nitronaphthalimides with intercalative properties. A phase I study with a conventional escalation scheme was developed. The schedule of drug administration was a daily x 5 days by short (1 h) intravenous (i.v.) infusion, every 21 days. Thirty evaluable patients were treated at doses from 15.4 mg/m2/d x 5 days to 138.6 mg/m2/d x 5 days. The study was interrupted due to appearance of central nervous system toxicity in 5 patients treated at doses above 118 mg/m2 x 5 days. This toxicity consisted firstly of loss of memory in all patients. It was irreversible and progressed in 3 patients to disorientation and confusion, leading to dementia in one of them. This was considered to be dose-limiting toxicity, and since it appeared to be related to the administration schedule, no further studies with short i.v. infusions of mitonafide are recommended. A phase I study utilizing a more desirable administration schedule over longer periods of time is ongoing in other centers.

Epidermal growth factor receptor (EGFr) and cytosolic (cER) and nuclear (nER) estradiol receptors were quantified in 220 primary breast cancers. The EGFr was significantly more frequent (chi 2 = 5.9; P less than 0.025) and its concentration was significantly higher (P less than 0.001) among ER- tumors than in ER+ tumors. There was a significantly greater proportion (chi 2 = 6.4; P less than 0.05) of node involvement in EGFr+/ER+ tumors than in EFGr-/ER+. Increases in the proportion of EGFr+ in ER- tumors are parallel to Scarff-Bloom scores (chi 2 = 6.1; P less than 0.05) and there is a significant trend (Spearman rs = 0.25; P less than 0.05) towards increased EGFr concentrations with histologic dedifferentiation. In ER+ tumors the median concentrations of EGFr in the different age groups show a linear correlation (LCC = 0.89; P less than 0.05) and follow a parallel profile with the medians of nER. These findings support the hypothesis that EGFr is a bad prognosis factor and suggest that EGFr expression and concentration in ER+ tumors might be considered an estrogenic action mediated through the binding of ER to their nuclear acceptors.