Pharmacokinetics of dacarbazine in the regional perfusion of extremities with melanoma.

BACKGROUND: The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required. METHODS: A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC. 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). 99(m)Tc (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity. RESULTS: High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity. CONCLUSIONS: High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion.

Breast cancer prevention trial.

The incidence of breast cancer continues to rise and now affects one in eight women, despite major early-detection efforts. The Breast Cancer Prevention Trial (BCPT), under the auspices of the National Surgical Adjuvant Breast and Bowel Project (NSABBP), will evaluate the effect of tamoxifen in reducing the incidence of invasive breast cancer, breast cancer mortality, cardiovascular mortality, and bone fractures. A total of 16,000 healthy women 35 years of age or older will be randomized to receive tamoxifen or a placebo over a five-year period. As of March 1993, 42% of the needed study participants had been enrolled in the trial. The University of Maryland is participating in the BCPT, and Maryland physicians can refer potential study participants to 12 locations throughout Maryland.

Survival differences between black and white women with breast cancer.

Several reports have indicated that black women with breast cancer have a poorer prognosis than white women. To investigate this phenomenon and to identify some of the underlying reasons, 172 patients with infiltrating ductal carcinoma of the breast, who were managed similarly, were studied. Survival analysis comparing the two populations with breast cancer revealed that white women had significantly longer overall survival (OS), P = 0.015 by Wilcoxon and 0.019 by log-rank, and borderline significantly longer disease-free survival (DFS), P = 0.04 by Wilcoxon and 0.07 by log-rank. While there was no significant difference in OS and DFS between the two groups with negative nodes, significantly poorer DFS and OS was noted in black patients with one to three positive lymph nodes compared to white patients, P = 0.008. The white patients had a higher incidence of hormone receptor-positive tumors, especially progesterone receptor (P = 0.0016). However, survival analysis failed to show any difference between the black and the white populations based on hormonal receptors. Such findings suggested that further investigation of other factor(s) is warranted.

Adjuvant immunotherapy in melanoma: a new approach.

Patients with metastatic cutaneous melanoma to two or more regional lymph nodes have an extremely poor prognosis despite radical lymphadenectomy. In an attempt to improve the survival and to determine the safety of a new method of tumor specific adjuvant immunotherapy in such a high risk group of patients, nine patients were studied. Three to four weeks after regional lymphadenectomy, each of them received a single intradermal injection of Bacillus Calmette-Guérin. Three weeks later, they were immunized by allogenic melanoma cells obtained from live donors with distant metastases. Each patient received three vaccinations, each from a different donor (except in one), to avoid development of HLA response, but maintaining exposure to melanoma antigens. No cultured melanoma cells were used. Each vaccine consisted of mitomycin-C treated tumor cells mixed with purified protein derivative (PPD) of tuberculin given intradermally once per month for 3 months. The patients were then observed with no further treatment. Utilizing the leukocyte migration inhibition test, there was some in vitro evidence of tumor specific cell mediated response which seemed to disappear 1-2 months postimmunization. At 5 years, five of the nine patients (55%) were alive free of disease. No autoimmune diseases were detected in any of the immunized patients. A major hindering factor for such an approach was the limited availability of the allogenic melanoma cells.

Prognostic value of initial mononucleated cell percentages in patients with epidermoid carcinoma of the head and neck.

It has been established that staging of squamous cell carcinoma of the head and neck at the time of diagnosis carries the most significant prognostic factor. Searching for other prognostic factors at the time of diagnosis, the percentages of lymphocytes and monocytes in the peripheral blood were studied. The results revealed that there were significantly higher lymphocyte values in patients without regional lymph node metastasis compared with those with such metastasis (p = 0.0064). On the other hand, higher monocyte values correlated with advanced stages of the disease. Patients with regional lymph node metastasis had higher monocyte values than those without nodal metastases. Furthermore, the incidence of recurrences and metastases during the first year was significantly lower in patients who had lymphocyte values of 30 percent or more when compared with those with values of less than 30 percent (p = 0.0003). In addition, all patients with early stages (I and II) of disease had less than 10 percent monocytes. These data suggest that initial high lymphocyte and low monocyte percentages carry a better prognosis. It seems that the percentage of mononucleated cells in the peripheral blood may have the second most important prognostic value.