Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.

Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.

Our experience with the combination of dacarbazine, carmustine, cisplatin with and without tamoxifen is reported. In our initial study, with all 4 drugs, we had an overall response rate of 50% with a complete response rate of 15%. Due to a high incidence of deep venous thrombosis and the lack of effectiveness of tamoxifen as a single agent, we deleted tamoxifen from the regimen and treated another 20 patients. Surprisingly, the response rate decreased to 10%. We then re-incorporated tamoxifen into the regimen and treated 25 additional patients. In this third group of patients we experienced an objective response rate of 52% with a complete response rate of 8%. Overall, 65 patients have been treated: 45 with and 20 without tamoxifen. Twenty-three (51%) patients treated with tamoxifen have responded, with 5 (11%) patients achieving a complete response. Only 2 (10%) patients treated without tamoxifen have responded. Despite the improvement in the response rate, a corresponding increase in survival has not been seen. Patients treated with tamoxifen had a mean survival of 10.8 (SD 13.6) months compared with a mean survival of 9.8 (SD 7.3) months for those treated without tamoxifen. The absence of survival advantage for the tamoxifen-treated patients may be due to early failure in the central nervous system. In 48% of the responding tamoxifen-treated patients, the first site of failure was the central nervous system, while systemic disease was still responding.

The combination of dacarbazine (DTIC, 220 mg/m2) and cisplatin (DDP, 25 mg/m2) IV daily for 3 days every 3 weeks, carmustine (BCNU, 150 mg/m2) IV every 6 weeks, and tamoxifen (TAM, 10 mg orally twice daily) produced a 50% objective response rate in patients with metastatic melanoma. Associated with this treatment, there was a high incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE). In an effort to reduce this toxicity, this regimen minus TAM was studied, and the results are reported. Twenty of twenty patients are evaluable for response and toxicity. There was one complete response (CR) lasting 5+ months and one partial response (PR) lasting 4+ months for an overall response rate of 10% (95% confidence limits, 1.23% to 31.70%). Two patients exhibited a mixed response and three patients developed disease stabilization lasting 4 to 10 months. Toxicity was similar to the original study except that no patients developed DVT or PE. This statistically significant (Fisher's exact test [two-tail] P = 0.008) decrease in the response rate by comparison with that achieved with the TAM-containing regimen may signal an essential role of TAM in this regimen. TAM may be acting in synergy with cisplatin through its calcium channel-blocking properties. TAM should be included as described in the initial reports, and the patients should be carefully observed for vascular complications.

Two hundred and ninety five Caucasian patients with histologically confirmed primary cutaneous malignant melanoma were evaluated. Twenty-three primary non-melanocytic, non-cutaneous malignant tumors occurred in 22 patients with a single primary cutaneous malignant melanoma for a prevalence of 8.2% (23/281). The observed number of non-melanocytic, non-cutaneous malignant neoplasms did not differ significantly from the expected number calculated on the basis of patient years at risk. Melanoma patients with primary non-melanocytic, non-cutaneous tumors were significantly older at the time of diagnosis of their melanoma than patients with melanoma alone. In addition, patients with multiple primary tumors were at risk a significantly longer period of time. With the possible exception of breast cancer, the association of cutaneous melanoma and additional non-melanocytic, non-cutaneous malignancies appears to be a random event. Nine additional primary cutaneous malignant melanomas were confirmed in eight melanoma patients for a prevalence of 3.4% (9/267). The observed number of additional primary melanomas was significantly greater than the expected number calculated on the basis of patient years at risk. Patients with multiple primary melanomas were not at risk significantly longer than patients with only one melanoma. It is likely that the development of additional primary melanomas in patients with an initial melanoma is not simply a random event, but represents a greater susceptibility of these patients' melanocytes to malignant transformation. survival of cancer patients, the second primary malignancy will become an increasing1 important clinical problem. In addition, the tudy of patients with multiple primary malign Tt neoplasms may yield some insight into the tiology of cancer. The objectives of the present study were: 1) To determine the prevalence and spectrum of non-melanocytic malignant neoplasms in patients with primary cutaneous melanoma. 2) To determine the prevalence of multiple primary cutaneous melanomas. 3) T o determine if the prevalence of multiple primary malignancies were greater than would occur by chance alone.